3D RNA and functional interactions from evolutionary couplings

PubMed Central

Weinreb, Caleb; Riesselman, Adam; Ingraham, John B.; Gross, Torsten; Sander, Chris; Marks, Debora S.

2016-01-01

Summary Non-coding RNAs are ubiquitous, but the discovery of new RNA gene sequences far outpaces research on their structure and functional interactions. We mine the evolutionary sequence record to derive precise information about function and structure of RNAs and RNA-protein complexes. As in protein structure prediction, we use maximum entropy global probability models of sequence co-variation to infer evolutionarily constrained nucleotide-nucleotide interactions within RNA molecules, and nucleotide-amino acid interactions in RNA-protein complexes. The predicted contacts allow all-atom blinded 3D structure prediction at good accuracy for several known RNA structures and RNA-protein complexes. For unknown structures, we predict contacts in 160 non-coding RNA families. Beyond 3D structure prediction, evolutionary couplings help identify important functional interactions, e.g., at switch points in riboswitches and at a complex nucleation site in HIV. Aided by accelerating sequence accumulation, evolutionary coupling analysis can accelerate the discovery of functional interactions and 3D structures involving RNA. PMID:27087444

A Prediction Model for Functional Outcomes in Spinal Cord Disorder Patients Using Gaussian Process Regression.

PubMed

Lee, Sunghoon Ivan; Mortazavi, Bobak; Hoffman, Haydn A; Lu, Derek S; Li, Charles; Paak, Brian H; Garst, Jordan H; Razaghy, Mehrdad; Espinal, Marie; Park, Eunjeong; Lu, Daniel C; Sarrafzadeh, Majid

2016-01-01

Predicting the functional outcomes of spinal cord disorder patients after medical treatments, such as a surgical operation, has always been of great interest. Accurate posttreatment prediction is especially beneficial for clinicians, patients, care givers, and therapists. This paper introduces a prediction method for postoperative functional outcomes by a novel use of Gaussian process regression. The proposed method specifically considers the restricted value range of the target variables by modeling the Gaussian process based on a truncated Normal distribution, which significantly improves the prediction results. The prediction has been made in assistance with target tracking examinations using a highly portable and inexpensive handgrip device, which greatly contributes to the prediction performance. The proposed method has been validated through a dataset collected from a clinical cohort pilot involving 15 patients with cervical spinal cord disorder. The results show that the proposed method can accurately predict postoperative functional outcomes, Oswestry disability index and target tracking scores, based on the patient's preoperative information with a mean absolute error of 0.079 and 0.014 (out of 1.0), respectively.

Linking Compositional and Functional Predictions to Decipher the Biogeochemical Significance in DFAA Turnover of Abundant Bacterioplankton Lineages in the North Sea.

PubMed

Wemheuer, Bernd; Wemheuer, Franziska; Meier, Dimitri; Billerbeck, Sara; Giebel, Helge-Ansgar; Simon, Meinhard; Scherber, Christoph; Daniel, Rolf

2017-11-05

Deciphering the ecological traits of abundant marine bacteria is a major challenge in marine microbial ecology. In the current study, we linked compositional and functional predictions to elucidate such traits for abundant bacterioplankton lineages in the North Sea. For this purpose, we investigated entire and active bacterioplankton composition along a transect ranging from the German Bight to the northern North Sea by pyrotag sequencing of bacterial 16S rRNA genes and transcripts. Functional profiles were inferred from 16S rRNA data using Tax4Fun. Bacterioplankton communities were dominated by well-known marine lineages including clusters/genera that are affiliated with the Roseobacter group and the Flavobacteria . Variations in community composition and function were significantly explained by measured environmental and microbial properties. Turnover of dissolved free amino acids (DFAA) showed the strongest correlation to community composition and function. We applied multinomial models, which enabled us to identify bacterial lineages involved in DFAA turnover. For instance, the genus Planktomarina was more abundant at higher DFAA turnover rates, suggesting its vital role in amino acid degradation. Functional predictions further indicated that Planktomarina is involved in leucine and isoleucine degradation. Overall, our results provide novel insights into the biogeochemical significance of abundant bacterioplankton lineages in the North Sea.

Computation of Standard Errors

PubMed Central

Dowd, Bryan E; Greene, William H; Norton, Edward C

2014-01-01

Objectives We discuss the problem of computing the standard errors of functions involving estimated parameters and provide the relevant computer code for three different computational approaches using two popular computer packages. Study Design We show how to compute the standard errors of several functions of interest: the predicted value of the dependent variable for a particular subject, and the effect of a change in an explanatory variable on the predicted value of the dependent variable for an individual subject and average effect for a sample of subjects. Empirical Application Using a publicly available dataset, we explain three different methods of computing standard errors: the delta method, Krinsky–Robb, and bootstrapping. We provide computer code for Stata 12 and LIMDEP 10/NLOGIT 5. Conclusions In most applications, choice of the computational method for standard errors of functions of estimated parameters is a matter of convenience. However, when computing standard errors of the sample average of functions that involve both estimated parameters and nonstochastic explanatory variables, it is important to consider the sources of variation in the function's values. PMID:24800304

Method and apparatus for determination of mechanical properties of functionally-graded materials

DOEpatents

Giannakopoulos, Antonios E.; Suresh, Subra

1999-01-01

Techniques for the determination of mechanical properties of homogenous or functionally-graded materials from indentation testing are presented. The technique is applicable to indentation on the nano-scale through the macro-scale including the geological scale. The technique involves creating a predictive load/depth relationship for a sample, providing an experimental load/depth relationship, comparing the experimental data to the predictive data, and determining a physical characteristic from the comparison.

The habenula encodes negative motivational value associated with primary punishment in humans.

PubMed

Lawson, Rebecca P; Seymour, Ben; Loh, Eleanor; Lutti, Antoine; Dolan, Raymond J; Dayan, Peter; Weiskopf, Nikolaus; Roiser, Jonathan P

2014-08-12

Learning what to approach, and what to avoid, involves assigning value to environmental cues that predict positive and negative events. Studies in animals indicate that the lateral habenula encodes the previously learned negative motivational value of stimuli. However, involvement of the habenula in dynamic trial-by-trial aversive learning has not been assessed, and the functional role of this structure in humans remains poorly characterized, in part, due to its small size. Using high-resolution functional neuroimaging and computational modeling of reinforcement learning, we demonstrate positive habenula responses to the dynamically changing values of cues signaling painful electric shocks, which predict behavioral suppression of responses to those cues across individuals. By contrast, negative habenula responses to monetary reward cue values predict behavioral invigoration. Our findings show that the habenula plays a key role in an online aversive learning system and in generating associated motivated behavior in humans.

Detecting Controller Malfunctions in Electromagnetic Environments. Part 1; Modeling and Estimation of Nominal System Function

NASA Technical Reports Server (NTRS)

Weinstein, Bernice

1999-01-01

A strategy for detecting control law calculation errors in critical flight control computers during laboratory validation testing is presented. This paper addresses Part I of the detection strategy which involves the use of modeling of the aircraft control laws and the design of Kalman filters to predict the correct control commands. Part II of the strategy which involves the use of the predicted control commands to detect control command errors is presented in the companion paper.

Functional traits determine plant co-occurrence more than environment or evolutionary relatedness in global drylands.

PubMed

Soliveres, Santiago; Maestre, Fernando T; Bowker, Matthew A; Torices, Rubén; Quero, José L; García-Gómez, Miguel; Cabrera, Omar; Cea, Alex; Coaguila, Daniel; Eldridge, David J; Espinosa, Carlos I; Hemmings, Frank; Monerris, Jorge J; Tighe, Matthew; Delgado-Baquerizo, Manuel; Escolar, Cristina; García-Palacios, Pablo; Gozalo, Beatriz; Ochoa, Victoria; Blones, Julio; Derak, Mchich; Ghiloufi, Wahida; Gutiérrez, Julio R; Hernández, Rosa M; Noumi, Zouhaier

2014-08-20

Plant-plant interactions are driven by environmental conditions, evolutionary relationships (ER) and the functional traits of the plants involved. However, studies addressing the relative importance of these drivers are rare, but crucial to improve our predictions of the effects of plant-plant interactions on plant communities and of how they respond to differing environmental conditions. To analyze the relative importance of -and interrelationships among- these factors as drivers of plant-plant interactions, we analyzed perennial plant co-occurrence at 106 dryland plant communities established across rainfall gradients in nine countries. We used structural equation modeling to disentangle the relationships between environmental conditions (aridity and soil fertility), functional traits extracted from the literature, and ER, and to assess their relative importance as drivers of the 929 pairwise plant-plant co-occurrence levels measured. Functional traits, specifically facilitated plants' height and nurse growth form, were of primary importance, and modulated the effect of the environment and ER on plant-plant interactions. Environmental conditions and ER were important mainly for those interactions involving woody and graminoid nurses, respectively. The relative importance of different plant-plant interaction drivers (ER, functional traits, and the environment) varied depending on the region considered, illustrating the difficulty of predicting the outcome of plant-plant interactions at broader spatial scales. In our global-scale study on drylands, plant-plant interactions were more strongly related to functional traits of the species involved than to the environmental variables considered. Thus, moving to a trait-based facilitation/competition approach help to predict that: 1) positive plant-plant interactions are more likely to occur for taller facilitated species in drylands, and 2) plant-plant interactions within woody-dominated ecosystems might be more sensitive to changing environmental conditions than those within grasslands. By providing insights on which species are likely to better perform beneath a given neighbour, our results will also help to succeed in restoration practices involving the use of nurse plants.

Functional traits determine plant co-occurrence more than environment or evolutionary relatedness in global drylands

PubMed Central

Soliveres, Santiago; Maestre, Fernando T.; Bowker, Matthew A.; Torices, Rubén; Quero, José L.; García-Gómez, Miguel; Cabrera, Omar; Cea, Alex; Coaguila, Daniel; Eldridge, David J.; Espinosa, Carlos I.; Hemmings, Frank; Monerris, Jorge J.; Tighe, Matthew; Delgado-Baquerizo, Manuel; Escolar, Cristina; García-Palacios, Pablo; Gozalo, Beatriz; Ochoa, Victoria; Blones, Julio; Derak, Mchich; Ghiloufi, Wahida; Gutiérrez, Julio R.; Hernández, Rosa M.; Noumi, Zouhaier

2015-01-01

Plant-plant interactions are driven by environmental conditions, evolutionary relationships (ER) and the functional traits of the plants involved. However, studies addressing the relative importance of these drivers are rare, but crucial to improve our predictions of the effects of plant-plant interactions on plant communities and of how they respond to differing environmental conditions. To analyze the relative importance of –and interrelationships among– these factors as drivers of plant-plant interactions, we analyzed perennial plant co-occurrence at 106 dryland plant communities established across rainfall gradients in nine countries. We used structural equation modeling to disentangle the relationships between environmental conditions (aridity and soil fertility), functional traits extracted from the literature, and ER, and to assess their relative importance as drivers of the 929 pairwise plant-plant co-occurrence levels measured. Functional traits, specifically facilitated plants’ height and nurse growth form, were of primary importance, and modulated the effect of the environment and ER on plant-plant interactions. Environmental conditions and ER were important mainly for those interactions involving woody and graminoid nurses, respectively. The relative importance of different plant-plant interaction drivers (ER, functional traits, and the environment) varied depending on the region considered, illustrating the difficulty of predicting the outcome of plant-plant interactions at broader spatial scales. In our global-scale study on drylands, plant-plant interactions were more strongly related to functional traits of the species involved than to the environmental variables considered. Thus, moving to a trait-based facilitation/competition approach help to predict that: 1) positive plant-plant interactions are more likely to occur for taller facilitated species in drylands, and 2) plant-plant interactions within woody-dominated ecosystems might be more sensitive to changing environmental conditions than those within grasslands. By providing insights on which species are likely to better perform beneath a given neighbour, our results will also help to succeed in restoration practices involving the use of nurse plants. PMID:25914604

Intelligence, creativity, and cognitive control: The common and differential involvement of executive functions in intelligence and creativity

PubMed Central

Benedek, Mathias; Jauk, Emanuel; Sommer, Markus; Arendasy, Martin; Neubauer, Aljoscha C.

2014-01-01

Intelligence and creativity are known to be correlated constructs suggesting that they share a common cognitive basis. The present study assessed three specific executive abilities – updating, shifting, and inhibition – and examined their common and differential relations to fluid intelligence and creativity (i.e., divergent thinking ability) within a latent variable model approach. Additionally, it was tested whether the correlation of fluid intelligence and creativity can be explained by a common executive involvement. As expected, fluid intelligence was strongly predicted by updating, but not by shifting or inhibition. Creativity was predicted by updating and inhibition, but not by shifting. Moreover, updating (and the personality factor openness) was found to explain a relevant part of the shared variance between intelligence and creativity. The findings provide direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity. PMID:25278640

A computational substrate for incentive salience.

PubMed

McClure, Samuel M; Daw, Nathaniel D; Montague, P Read

2003-08-01

Theories of dopamine function are at a crossroads. Computational models derived from single-unit recordings capture changes in dopaminergic neuron firing rate as a prediction error signal. These models employ the prediction error signal in two roles: learning to predict future rewarding events and biasing action choice. Conversely, pharmacological inhibition or lesion of dopaminergic neuron function diminishes the ability of an animal to motivate behaviors directed at acquiring rewards. These lesion experiments have raised the possibility that dopamine release encodes a measure of the incentive value of a contemplated behavioral act. The most complete psychological idea that captures this notion frames the dopamine signal as carrying 'incentive salience'. On the surface, these two competing accounts of dopamine function seem incommensurate. To the contrary, we demonstrate that both of these functions can be captured in a single computational model of the involvement of dopamine in reward prediction for the purpose of reward seeking.

Parent Involvement and Children's Academic and Social Development in Elementary School

PubMed Central

El Nokali, Nermeen E.; Bachman, Heather J.; Votruba-Drzal, Elizabeth

2010-01-01

Data from the NICHD Study of Early Childcare and Youth Development (N= 1364) were used to investigate children's trajectories of academic and social development across first, third and fifth grade. Hierarchical linear modeling was used to examine within- and between-child associations among maternal- and teacher-reports of parent involvement and children's standardized achievement scores, social skills, and problem behaviors. Findings suggest that within-child improvements in parent involvement predict declines in problem behaviors and improvements in social skills but do not predict changes in achievement. Between-child analyses demonstrated that children with highly involved parents had enhanced social functioning and fewer behavior problems. Similar patterns of findings emerged for teacher- and parent-reports of parent involvement. Implications for policy and practice are discussed. PMID:20573118

Parents' Involvement in Children's Learning in the United States and China: Implications for Children's Academic and Emotional Adjustment

PubMed Central

Cheung, Cecilia Sin-Sze; Pomerantz, Eva M.

2011-01-01

This research examined parents' involvement in children's learning in the United States and China. Beginning in seventh grade, 825 American and Chinese children (mean age = 12.74 years) reported on their parents' involvement in their learning as well as their parents' psychological control and autonomy support every six months until the end of eighth grade. Information on children's academic and emotional adjustment was obtained. American (vs. Chinese) parents' involvement was associated less with their control and more with their autonomy support. Despite these different associations, parents' heightened involvement predicted children's enhanced engagement and achievement similarly in the United States and China. However, it predicted enhanced perceptions of competence and positive emotional functioning more strongly in the United States than China. PMID:21418057

Presurgery resting-state local graph-theory measures predict neurocognitive outcomes after brain surgery in temporal lobe epilepsy.

PubMed

Doucet, Gaelle E; Rider, Robert; Taylor, Nathan; Skidmore, Christopher; Sharan, Ashwini; Sperling, Michael; Tracy, Joseph I

2015-04-01

This study determined the ability of resting-state functional connectivity (rsFC) graph-theory measures to predict neurocognitive status postsurgery in patients with temporal lobe epilepsy (TLE) who underwent anterior temporal lobectomy (ATL). A presurgical resting-state functional magnetic resonance imaging (fMRI) condition was collected in 16 left and 16 right TLE patients who underwent ATL. In addition, patients received neuropsychological testing pre- and postsurgery in verbal and nonverbal episodic memory, language, working memory, and attention domains. Regarding the functional data, we investigated three graph-theory properties (local efficiency, distance, and participation), measuring segregation, integration and centrality, respectively. These measures were only computed in regions of functional relevance to the ictal pathology, or the cognitive domain. Linear regression analyses were computed to predict the change in each neurocognitive domain. Our analyses revealed that cognitive outcome was successfully predicted with at least 68% of the variance explained in each model, for both TLE groups. The only model not significantly predictive involved nonverbal episodic memory outcome in right TLE. Measures involving the healthy hippocampus were the most common among the predictors, suggesting that enhanced integration of this structure with the rest of the brain may improve cognitive outcomes. Regardless of TLE group, left inferior frontal regions were the best predictors of language outcome. Working memory outcome was predicted mostly by right-sided regions, in both groups. Overall, the results indicated our integration measure was the most predictive of neurocognitive outcome. In contrast, our segregation measure was the least predictive. This study provides evidence that presurgery rsFC measures may help determine neurocognitive outcomes following ATL. The results have implications for refining our understanding of compensatory reorganization and predicting cognitive outcome after ATL. The results are encouraging with regard to the clinical relevance of using graph-theory measures in presurgical algorithms in the setting of TLE. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

On the nonlocal predictions of quantum optics

NASA Technical Reports Server (NTRS)

Marshall, Trevor W.; Santos, Emilio; Vidiella-Barranco, Antonio

1994-01-01

We give a definition of locality in quantum optics based upon Bell's work, and show that locality has been violated in no experiment performed up to now. We argue that the interpretation of the Wigner function as a probability density gives a very attractive local realistic picture of quantum optics provided that this function is nonnegative. We conjecture that this is the case for all states which can be realized in the laboratory. In particular, we believe that the usual representation of 'single photon states' by a Fock state of the Hilbert space is not correct and that a more physical, although less simple mathematically, representation involves density matrices. We study in some detail the experiment showing anticorrelation after a beam splitter and prove that it naturally involves a positive Wigner function. Our (quantum) predictions for this experiment disagree with the ones reported in the literature.

Nematode Damage Functions: The Problems of Experimental and Sampling Error

PubMed Central

Ferris, H.

1984-01-01

The development and use of pest damage functions involves measurement and experimental errors associated with cultural, environmental, and distributional factors. Damage predictions are more valuable if considered with associated probability. Collapsing population densities into a geometric series of population classes allows a pseudo-replication removal of experimental and sampling error in damage function development. Recognition of the nature of sampling error for aggregated populations allows assessment of probability associated with the population estimate. The product of the probabilities incorporated in the damage function and in the population estimate provides a basis for risk analysis of the yield loss prediction and the ensuing management decision. PMID:19295865

Genetic interaction networks: better understand to better predict

PubMed Central

Boucher, Benjamin; Jenna, Sarah

2013-01-01

A genetic interaction (GI) between two genes generally indicates that the phenotype of a double mutant differs from what is expected from each individual mutant. In the last decade, genome scale studies of quantitative GIs were completed using mainly synthetic genetic array technology and RNA interference in yeast and Caenorhabditis elegans. These studies raised questions regarding the functional interpretation of GIs, the relationship of genetic and molecular interaction networks, the usefulness of GI networks to infer gene function and co-functionality, the evolutionary conservation of GI, etc. While GIs have been used for decades to dissect signaling pathways in genetic models, their functional interpretations are still not trivial. The existence of a GI between two genes does not necessarily imply that these two genes code for interacting proteins or that the two genes are even expressed in the same cell. In fact, a GI only implies that the two genes share a functional relationship. These two genes may be involved in the same biological process or pathway; or they may also be involved in compensatory pathways with unrelated apparent function. Considering the powerful opportunity to better understand gene function, genetic relationship, robustness and evolution, provided by a genome-wide mapping of GIs, several in silico approaches have been employed to predict GIs in unicellular and multicellular organisms. Most of these methods used weighted data integration. In this article, we will review the later knowledge acquired on GI networks in metazoans by looking more closely into their relationship with pathways, biological processes and molecular complexes but also into their modularity and organization. We will also review the different in silico methods developed to predict GIs and will discuss how the knowledge acquired on GI networks can be used to design predictive tools with higher performances. PMID:24381582

Emotion Regulation Predicts Pain and Functioning in Children With Juvenile Idiopathic Arthritis: An Electronic Diary Study

PubMed Central

Bromberg, Maggie H.; Anthony, Kelly K.; Gil, Karen M.; Franks, Lindsey; Schanberg, Laura E.

2012-01-01

Objectives This study utilized e-diaries to evaluate whether components of emotion regulation predict daily pain and function in children with juvenile idiopathic arthritis (JIA). Methods 43 children ages 8–17 years and their caregivers provided baseline reports of child emotion regulation. Children then completed thrice daily e-diary assessments of emotion, pain, and activity involvement for 28 days. E-diary ratings of negative and positive emotions were used to calculate emotion variability and to infer adaptive emotion modulation following periods of high or low emotion intensity. Hierarchical linear models were used to evaluate how emotion regulation related to pain and function. Results The attenuation of negative emotion following a period of high negative emotion predicted reduced pain; greater variability of negative emotion predicted higher pain and increased activity limitation. Indices of positive emotion regulation also significantly predicted pain. Conclusions Components of emotion regulation as captured by e-diaries predict important health outcomes in children with JIA. PMID:22037006

Fine-Motor Skill Deficits in Childhood Predict Adulthood Tic Severity and Global Psychosocial Functioning in Tourette's Syndrome

ERIC Educational Resources Information Center

Bloch, Michael H.; Sukhodolsky, Denis G.; Leckman, James F.; Schultz, Robert T.

2006-01-01

Background: Most children with Tourette's syndrome (TS) experience a significant decline in tic symptoms during adolescence. Currently no clinical measures have been identified that can predict whose tic symptoms will persist into adulthood. Patients with TS have deficits on neuropsychological tests involving fine-motor coordination and…

Deciphering RNA Regulatory Elements Involved in the Developmental and Environmental Gene Regulation of Trypanosoma brucei.

PubMed

Gazestani, Vahid H; Salavati, Reza

2015-01-01

Trypanosoma brucei is a vector-borne parasite with intricate life cycle that can cause serious diseases in humans and animals. This pathogen relies on fine regulation of gene expression to respond and adapt to variable environments, with implications in transmission and infectivity. However, the involved regulatory elements and their mechanisms of actions are largely unknown. Here, benefiting from a new graph-based approach for finding functional regulatory elements in RNA (GRAFFER), we have predicted 88 new RNA regulatory elements that are potentially involved in the gene regulatory network of T. brucei. We show that many of these newly predicted elements are responsive to both transcriptomic and proteomic changes during the life cycle of the parasite. Moreover, we found that 11 of predicted elements strikingly resemble previously identified regulatory elements for the parasite. Additionally, comparison with previously predicted motifs on T. brucei suggested the superior performance of our approach based on the current limited knowledge of regulatory elements in T. brucei.

Appearance Matters: Neural Correlates of Food Choice and Packaging Aesthetics

PubMed Central

Van der Laan, Laura N.; De Ridder, Denise T. D.; Viergever, Max A.; Smeets, Paul A. M.

2012-01-01

Neuro-imaging holds great potential for predicting choice behavior from brain responses. In this study we used both traditional mass-univariate and state-of-the-art multivariate pattern analysis to establish which brain regions respond to preferred packages and to what extent neural activation patterns can predict realistic low-involvement consumer choices. More specifically, this was assessed in the context of package-induced binary food choices. Mass-univariate analyses showed that several regions, among which the bilateral striatum, were more strongly activated in response to preferred food packages. Food choices could be predicted with an accuracy of up to 61.2% by activation patterns in brain regions previously found to be involved in healthy food choices (superior frontal gyrus) and visual processing (middle occipital gyrus). In conclusion, this study shows that mass-univariate analysis can detect small package-induced differences in product preference and that MVPA can successfully predict realistic low-involvement consumer choices from functional MRI data. PMID:22848586

PRISM offers a comprehensive genomic approach to transcription factor function prediction

PubMed Central

Wenger, Aaron M.; Clarke, Shoa L.; Guturu, Harendra; Chen, Jenny; Schaar, Bruce T.; McLean, Cory Y.; Bejerano, Gill

2013-01-01

The human genome encodes 1500–2000 different transcription factors (TFs). ChIP-seq is revealing the global binding profiles of a fraction of TFs in a fraction of their biological contexts. These data show that the majority of TFs bind directly next to a large number of context-relevant target genes, that most binding is distal, and that binding is context specific. Because of the effort and cost involved, ChIP-seq is seldom used in search of novel TF function. Such exploration is instead done using expression perturbation and genetic screens. Here we propose a comprehensive computational framework for transcription factor function prediction. We curate 332 high-quality nonredundant TF binding motifs that represent all major DNA binding domains, and improve cross-species conserved binding site prediction to obtain 3.3 million conserved, mostly distal, binding site predictions. We combine these with 2.4 million facts about all human and mouse gene functions, in a novel statistical framework, in search of enrichments of particular motifs next to groups of target genes of particular functions. Rigorous parameter tuning and a harsh null are used to minimize false positives. Our novel PRISM (predicting regulatory information from single motifs) approach obtains 2543 TF function predictions in a large variety of contexts, at a false discovery rate of 16%. The predictions are highly enriched for validated TF roles, and 45 of 67 (67%) tested binding site regions in five different contexts act as enhancers in functionally matched cells. PMID:23382538

Pretraining Cortical Thickness Predicts Subsequent Perceptual Learning Rate in a Visual Search Task.

PubMed

Frank, Sebastian M; Reavis, Eric A; Greenlee, Mark W; Tse, Peter U

2016-03-01

We report that preexisting individual differences in the cortical thickness of brain areas involved in a perceptual learning task predict the subsequent perceptual learning rate. Participants trained in a motion-discrimination task involving visual search for a "V"-shaped target motion trajectory among inverted "V"-shaped distractor trajectories. Motion-sensitive area MT+ (V5) was functionally identified as critical to the task: after 3 weeks of training, activity increased in MT+ during task performance, as measured by functional magnetic resonance imaging. We computed the cortical thickness of MT+ from anatomical magnetic resonance imaging volumes collected before training started, and found that it significantly predicted subsequent perceptual learning rates in the visual search task. Participants with thicker neocortex in MT+ before training learned faster than those with thinner neocortex in that area. A similar association between cortical thickness and training success was also found in posterior parietal cortex (PPC). © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Decoding genes with coexpression networks and metabolomics - 'majority report by precogs'.

PubMed

Saito, Kazuki; Hirai, Masami Y; Yonekura-Sakakibara, Keiko

2008-01-01

Following the sequencing of whole genomes of model plants, high-throughput decoding of gene function is a major challenge in modern plant biology. In view of remarkable technical advances in transcriptomics and metabolomics, integrated analysis of these 'omics' by data-mining informatics is an excellent tool for prediction and identification of gene function, particularly for genes involved in complicated metabolic pathways. The availability of Arabidopsis public transcriptome datasets containing data of >1000 microarrays reinforces the potential for prediction of gene function by transcriptome coexpression analysis. Here, we review the strategy of combining transcriptome and metabolome as a powerful technology for studying the functional genomics of model plants and also crop and medicinal plants.

Molecular characterization of HIV-1 Nef and ACOT8 interaction: insights from in silico structural predictions and in vitro functional assays

NASA Astrophysics Data System (ADS)

Serena, Michela; Giorgetti, Alejandro; Busato, Mirko; Gasparini, Francesca; Diani, Erica; Romanelli, Maria Grazia; Zipeto, Donato

2016-03-01

HIV-1 Nef interacts with several cellular proteins, among which the human peroxisomal thioesterase 8 (ACOT8). This interaction may be involved in the endocytosis regulation of membrane proteins and might modulate lipid composition in membrane rafts. Nef regions involved in the interaction have been experimentally characterized, whereas structural details of the ACOT8 protein are unknown. The lack of structural information hampers the comprehension of the functional consequences of the complex formation during HIV-1 infection. We modelled, through in silico predictions, the ACOT8 structure and we observed a high charge complementarity between Nef and ACOT8 surfaces, which allowed the identification of the ACOT8 putative contact points involved in the interaction. The predictions were validated by in vitro assays through the development of ACOT8 deletion mutants. Coimmunoprecipitation and immunofluorescence analyses showed that ACOT8 Arg45-Phe55 and Arg86-Pro93 regions are involved in Nef association. In addition, K91S mutation abrogated the interaction with Nef, indicating that Lys91 plays a key role in the interaction. Finally, when associated with ACOT8, Nef may be preserved from degradation. These findings improve the comprehension of the association between HIV-1 Nef and ACOT8, helping elucidating the biological effect of their interaction.

Utility of functioning in predicting costs of care for patients with mood and anxiety disorders: a prospective cohort study

PubMed Central

Cieza, Alarcos; Baldwin, David S.

2017-01-01

Development of payment systems for mental health services has been hindered by limited evidence for the utility of diagnosis or symptoms in predicting costs of care. We investigated the utility of functioning information in predicting costs for patients with mood and anxiety disorders. This was a prospective cohort study involving 102 adult patients attending a tertiary referral specialist clinic for mood and anxiety disorders. The main outcome was total costs, calculated by applying unit costs to healthcare use data. After adjusting for covariates, a significant total costs association was yielded for functioning (eβ=1.02; 95% confidence interval: 1.01–1.03), but not depressive symptom severity or anxiety symptom severity. When we accounted for the correlations between the main independent variables by constructing an abridged functioning metric, a significant total costs association was again yielded for functioning (eβ=1.04; 95% confidence interval: 1.01–1.09), but not symptom severity. The utility of functioning in predicting costs for patients with mood and anxiety disorders was supported. Functioning information could be useful within mental health payment systems. PMID:28383309

Comparison of two bioinformatics tools used to characterize the microbial diversity and predictive functional attributes of microbial mats from Lake Obersee, Antarctica.

PubMed

Koo, Hyunmin; Hakim, Joseph A; Morrow, Casey D; Eipers, Peter G; Davila, Alfonso; Andersen, Dale T; Bej, Asim K

2017-09-01

In this study, using NextGen sequencing of the collective 16S rRNA genes obtained from two sets of samples collected from Lake Obersee, Antarctica, we compared and contrasted two bioinformatics tools, PICRUSt and Tax4Fun. We then developed an R script to assess the taxonomic and predictive functional profiles of the microbial communities within the samples. Taxa such as Pseudoxanthomonas, Planctomycetaceae, Cyanobacteria Subsection III, Nitrosomonadaceae, Leptothrix, and Rhodobacter were exclusively identified by Tax4Fun that uses SILVA database; whereas PICRUSt that uses Greengenes database uniquely identified Pirellulaceae, Gemmatimonadetes A1-B1, Pseudanabaena, Salinibacterium and Sinobacteraceae. Predictive functional profiling of the microbial communities using Tax4Fun and PICRUSt separately revealed common metabolic capabilities, while also showing specific functional IDs not shared between the two approaches. Combining these functional predictions using a customized R script revealed a more inclusive metabolic profile, such as hydrolases, oxidoreductases, transferases; enzymes involved in carbohydrate and amino acid metabolisms; and membrane transport proteins known for nutrient uptake from the surrounding environment. Our results present the first molecular-phylogenetic characterization and predictive functional profiles of the microbial mat communities in Lake Obersee, while demonstrating the efficacy of combining both the taxonomic assignment information and functional IDs using the R script created in this study for a more streamlined evaluation of predictive functional profiles of microbial communities. Copyright © 2017 Elsevier B.V. All rights reserved.

Optimization of structures on the basis of fracture mechanics and reliability criteria

NASA Technical Reports Server (NTRS)

Heer, E.; Yang, J. N.

1973-01-01

Systematic summary of factors which are involved in optimization of given structural configuration is part of report resulting from study of analysis of objective function. Predicted reliability of performance of finished structure is sharply dependent upon results of coupon tests. Optimization analysis developed by study also involves expected cost of proof testing.

Improving prediction of heterodimeric protein complexes using combination with pairwise kernel.

PubMed

Ruan, Peiying; Hayashida, Morihiro; Akutsu, Tatsuya; Vert, Jean-Philippe

2018-02-19

Since many proteins become functional only after they interact with their partner proteins and form protein complexes, it is essential to identify the sets of proteins that form complexes. Therefore, several computational methods have been proposed to predict complexes from the topology and structure of experimental protein-protein interaction (PPI) network. These methods work well to predict complexes involving at least three proteins, but generally fail at identifying complexes involving only two different proteins, called heterodimeric complexes or heterodimers. There is however an urgent need for efficient methods to predict heterodimers, since the majority of known protein complexes are precisely heterodimers. In this paper, we use three promising kernel functions, Min kernel and two pairwise kernels, which are Metric Learning Pairwise Kernel (MLPK) and Tensor Product Pairwise Kernel (TPPK). We also consider the normalization forms of Min kernel. Then, we combine Min kernel or its normalization form and one of the pairwise kernels by plugging. We applied kernels based on PPI, domain, phylogenetic profile, and subcellular localization properties to predicting heterodimers. Then, we evaluate our method by employing C-Support Vector Classification (C-SVC), carrying out 10-fold cross-validation, and calculating the average F-measures. The results suggest that the combination of normalized-Min-kernel and MLPK leads to the best F-measure and improved the performance of our previous work, which had been the best existing method so far. We propose new methods to predict heterodimers, using a machine learning-based approach. We train a support vector machine (SVM) to discriminate interacting vs non-interacting protein pairs, based on informations extracted from PPI, domain, phylogenetic profiles and subcellular localization. We evaluate in detail new kernel functions to encode these data, and report prediction performance that outperforms the state-of-the-art.

Year 2 Report: Protein Function Prediction Platform

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

Zhou, C E

2012-04-27

Upon completion of our second year of development in a 3-year development cycle, we have completed a prototype protein structure-function annotation and function prediction system: Protein Function Prediction (PFP) platform (v.0.5). We have met our milestones for Years 1 and 2 and are positioned to continue development in completion of our original statement of work, or a reasonable modification thereof, in service to DTRA Programs involved in diagnostics and medical countermeasures research and development. The PFP platform is a multi-scale computational modeling system for protein structure-function annotation and function prediction. As of this writing, PFP is the only existing fullymore » automated, high-throughput, multi-scale modeling, whole-proteome annotation platform, and represents a significant advance in the field of genome annotation (Fig. 1). PFP modules perform protein functional annotations at the sequence, systems biology, protein structure, and atomistic levels of biological complexity (Fig. 2). Because these approaches provide orthogonal means of characterizing proteins and suggesting protein function, PFP processing maximizes the protein functional information that can currently be gained by computational means. Comprehensive annotation of pathogen genomes is essential for bio-defense applications in pathogen characterization, threat assessment, and medical countermeasure design and development in that it can short-cut the time and effort required to select and characterize protein biomarkers.« less

Functional annotation of chemical libraries across diverse biological processes.

PubMed

Piotrowski, Jeff S; Li, Sheena C; Deshpande, Raamesh; Simpkins, Scott W; Nelson, Justin; Yashiroda, Yoko; Barber, Jacqueline M; Safizadeh, Hamid; Wilson, Erin; Okada, Hiroki; Gebre, Abraham A; Kubo, Karen; Torres, Nikko P; LeBlanc, Marissa A; Andrusiak, Kerry; Okamoto, Reika; Yoshimura, Mami; DeRango-Adem, Eva; van Leeuwen, Jolanda; Shirahige, Katsuhiko; Baryshnikova, Anastasia; Brown, Grant W; Hirano, Hiroyuki; Costanzo, Michael; Andrews, Brenda; Ohya, Yoshikazu; Osada, Hiroyuki; Yoshida, Minoru; Myers, Chad L; Boone, Charles

2017-09-01

Chemical-genetic approaches offer the potential for unbiased functional annotation of chemical libraries. Mutations can alter the response of cells in the presence of a compound, revealing chemical-genetic interactions that can elucidate a compound's mode of action. We developed a highly parallel, unbiased yeast chemical-genetic screening system involving three key components. First, in a drug-sensitive genetic background, we constructed an optimized diagnostic mutant collection that is predictive for all major yeast biological processes. Second, we implemented a multiplexed (768-plex) barcode-sequencing protocol, enabling the assembly of thousands of chemical-genetic profiles. Finally, based on comparison of the chemical-genetic profiles with a compendium of genome-wide genetic interaction profiles, we predicted compound functionality. Applying this high-throughput approach, we screened seven different compound libraries and annotated their functional diversity. We further validated biological process predictions, prioritized a diverse set of compounds, and identified compounds that appear to have dual modes of action.

Predicting fibromyalgia, a narrative review: are we better than fools and children?

PubMed

Ablin, J N; Buskila, D

2014-09-01

Fibromyalgia syndrome (FMS) is a common and intriguing condition, manifest by chronic pain and fatigue. Although the pathogenesis of FMS is not yet completely understood, predicting the future development of FMS and chronic pain is a major challenge with great potential advantages, both from an individual as well as an epidemiological standpoint. Current knowledge indicates a genetic underpinning for FMS, and as increasing data are accumulated regarding the genetics involved, the prospect of utilizing these data for prediction becomes ever more attractive. The co-existence of FMS with multiple other functional disorders indicates that the clinical identification of such symptom constellations in a patient can alert the physician to the future development of FMS. Hypermobility syndrome is another clinical (as well as genetic) phenotype that has emerged as a risk factor for the development of FMS. Stressful events, including early life trauma, are also harbingers of the future development of FMS. Functional neuroimaging may help to elucidate the neural processes involved in central sensitization, and may ultimately also evolve into markers of predictive value. Last but not least, obesity and disturbed sleep are clinical (inter-related) features relevant for this spectrum. Future efforts will aim at integrating genetic, clinical and physiological data in the prediction of FMS and chronic pain. © 2014 European Pain Federation - EFIC®

Muscle MRI and functional outcome measures in Becker muscular dystrophy.

PubMed

Barp, Andrea; Bello, Luca; Caumo, Luca; Campadello, Paola; Semplicini, Claudio; Lazzarotto, Annalisa; Sorarù, Gianni; Calore, Chiara; Rampado, Alessandro; Motta, Raffaella; Stramare, Roberto; Pegoraro, Elena

2017-11-22

Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification. In this study, 51 molecularly confirmed BMD patients (aged 7-69 years) underwent muscle MRI and were evaluated with functional measures (NSAA and 6MWT) at the time of the MRI, and subsequently after one year. We confirmed a pattern of fatty substitution involving mainly the hip extensors and most thigh muscles. Severity of muscle fatty substitution was significantly correlated with specific DMD mutations: in particular, patients with an isolated deletion of exon 48, or deletions bordering exon 51, showed milder involvement. Fat infiltration scores correlated with baseline functional measures, and predicted changes after 1 year. We conclude that in BMD, skeletal muscle MRI not only strongly correlates with motor function, but also helps in predicting functional deterioration within a 12-month time frame.

The left inferior parietal lobe represents stored hand-postures for object use and action prediction

PubMed Central

van Elk, Michiel

2014-01-01

Action semantics enables us to plan actions with objects and to predict others' object-directed actions as well. Previous studies have suggested that action semantics are represented in a fronto-parietal action network that has also been implicated to play a role in action observation. In the present fMRI study it was investigated how activity within this network changes as a function of the predictability of an action involving multiple objects and requiring the use of action semantics. Participants performed an action prediction task in which they were required to anticipate the use of a centrally presented object that could be moved to an associated target object (e.g., hammer—nail). The availability of actor information (i.e., presenting a hand grasping the central object) and the number of possible target objects (i.e., 0, 1, or 2 target objects) were independently manipulated, resulting in different levels of predictability. It was found that making an action prediction based on actor information resulted in an increased activation in the extrastriate body area (EBA) and the fronto-parietal action observation network (AON). Predicting actions involving a target object resulted in increased activation in the bilateral IPL and frontal motor areas. Within the AON, activity in the left inferior parietal lobe (IPL) and the left premotor cortex (PMC) increased as a function of the level of action predictability. Together these findings suggest that the left IPL represents stored hand-postures that can be used for planning object-directed actions and for predicting other's actions as well. PMID:24795681

Predictive Mechanisms Are Not Involved the Same Way during Human-Human vs. Human-Machine Interactions: A Review

PubMed Central

Sahaï, Aïsha; Pacherie, Elisabeth; Grynszpan, Ouriel; Berberian, Bruno

2017-01-01

Nowadays, interactions with others do not only involve human peers but also automated systems. Many studies suggest that the motor predictive systems that are engaged during action execution are also involved during joint actions with peers and during other human generated action observation. Indeed, the comparator model hypothesis suggests that the comparison between a predicted state and an estimated real state enables motor control, and by a similar functioning, understanding and anticipating observed actions. Such a mechanism allows making predictions about an ongoing action, and is essential to action regulation, especially during joint actions with peers. Interestingly, the same comparison process has been shown to be involved in the construction of an individual's sense of agency, both for self-generated and observed other human generated actions. However, the implication of such predictive mechanisms during interactions with machines is not consensual, probably due to the high heterogeneousness of the automata used in the experimentations, from very simplistic devices to full humanoid robots. The discrepancies that are observed during human/machine interactions could arise from the absence of action/observation matching abilities when interacting with traditional low-level automata. Consistently, the difficulties to build a joint agency with this kind of machines could stem from the same problem. In this context, we aim to review the studies investigating predictive mechanisms during social interactions with humans and with automated artificial systems. We will start by presenting human data that show the involvement of predictions in action control and in the sense of agency during social interactions. Thereafter, we will confront this literature with data from the robotic field. Finally, we will address the upcoming issues in the field of robotics related to automated systems aimed at acting as collaborative agents. PMID:29081744

Network control principles predict neuron function in the Caenorhabditis elegans connectome

PubMed Central

Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-01-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social and technological networks1–3. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode C. elegans4–6, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires twelve neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation7–13, as well as one previously uncharacterised neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed, with single-cell ablations of DD04 or DD05, but not DD02 or DD03, specifically affecting posterior body movements. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterised connectomes. PMID:29045391

Network control principles predict neuron function in the Caenorhabditis elegans connectome

NASA Astrophysics Data System (ADS)

Yan, Gang; Vértes, Petra E.; Towlson, Emma K.; Chew, Yee Lian; Walker, Denise S.; Schafer, William R.; Barabási, Albert-László

2017-10-01

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Network control principles predict neuron function in the Caenorhabditis elegans connectome.

PubMed

Yan, Gang; Vértes, Petra E; Towlson, Emma K; Chew, Yee Lian; Walker, Denise S; Schafer, William R; Barabási, Albert-László

2017-10-26

Recent studies on the controllability of complex systems offer a powerful mathematical framework to systematically explore the structure-function relationship in biological, social, and technological networks. Despite theoretical advances, we lack direct experimental proof of the validity of these widely used control principles. Here we fill this gap by applying a control framework to the connectome of the nematode Caenorhabditis elegans, allowing us to predict the involvement of each C. elegans neuron in locomotor behaviours. We predict that control of the muscles or motor neurons requires 12 neuronal classes, which include neuronal groups previously implicated in locomotion by laser ablation, as well as one previously uncharacterized neuron, PDB. We validate this prediction experimentally, finding that the ablation of PDB leads to a significant loss of dorsoventral polarity in large body bends. Importantly, control principles also allow us to investigate the involvement of individual neurons within each neuronal class. For example, we predict that, within the class of DD motor neurons, only three (DD04, DD05, or DD06) should affect locomotion when ablated individually. This prediction is also confirmed; single cell ablations of DD04 or DD05 specifically affect posterior body movements, whereas ablations of DD02 or DD03 do not. Our predictions are robust to deletions of weak connections, missing connections, and rewired connections in the current connectome, indicating the potential applicability of this analytical framework to larger and less well-characterized connectomes.

Predicting taxonomic and functional structure of microbial communities in acid mine drainage

PubMed Central

Kuang, Jialiang; Huang, Linan; He, Zhili; Chen, Linxing; Hua, Zhengshuang; Jia, Pu; Li, Shengjin; Liu, Jun; Li, Jintian; Zhou, Jizhong; Shu, Wensheng

2016-01-01

Predicting the dynamics of community composition and functional attributes responding to environmental changes is an essential goal in community ecology but remains a major challenge, particularly in microbial ecology. Here, by targeting a model system with low species richness, we explore the spatial distribution of taxonomic and functional structure of 40 acid mine drainage (AMD) microbial communities across Southeast China profiled by 16S ribosomal RNA pyrosequencing and a comprehensive microarray (GeoChip). Similar environmentally dependent patterns of dominant microbial lineages and key functional genes were observed regardless of the large-scale geographical isolation. Functional and phylogenetic β-diversities were significantly correlated, whereas functional metabolic potentials were strongly influenced by environmental conditions and community taxonomic structure. Using advanced modeling approaches based on artificial neural networks, we successfully predicted the taxonomic and functional dynamics with significantly higher prediction accuracies of metabolic potentials (average Bray–Curtis similarity 87.8) as compared with relative microbial abundances (similarity 66.8), implying that natural AMD microbial assemblages may be better predicted at the functional genes level rather than at taxonomic level. Furthermore, relative metabolic potentials of genes involved in many key ecological functions (for example, nitrogen and phosphate utilization, metals resistance and stress response) were extrapolated to increase under more acidic and metal-rich conditions, indicating a critical strategy of stress adaptation in these extraordinary communities. Collectively, our findings indicate that natural selection rather than geographic distance has a more crucial role in shaping the taxonomic and functional patterns of AMD microbial community that readily predicted by modeling methods and suggest that the model-based approach is essential to better understand natural acidophilic microbial communities. PMID:26943622

Predicting taxonomic and functional structure of microbial communities in acid mine drainage.

PubMed

Kuang, Jialiang; Huang, Linan; He, Zhili; Chen, Linxing; Hua, Zhengshuang; Jia, Pu; Li, Shengjin; Liu, Jun; Li, Jintian; Zhou, Jizhong; Shu, Wensheng

2016-06-01

Predicting the dynamics of community composition and functional attributes responding to environmental changes is an essential goal in community ecology but remains a major challenge, particularly in microbial ecology. Here, by targeting a model system with low species richness, we explore the spatial distribution of taxonomic and functional structure of 40 acid mine drainage (AMD) microbial communities across Southeast China profiled by 16S ribosomal RNA pyrosequencing and a comprehensive microarray (GeoChip). Similar environmentally dependent patterns of dominant microbial lineages and key functional genes were observed regardless of the large-scale geographical isolation. Functional and phylogenetic β-diversities were significantly correlated, whereas functional metabolic potentials were strongly influenced by environmental conditions and community taxonomic structure. Using advanced modeling approaches based on artificial neural networks, we successfully predicted the taxonomic and functional dynamics with significantly higher prediction accuracies of metabolic potentials (average Bray-Curtis similarity 87.8) as compared with relative microbial abundances (similarity 66.8), implying that natural AMD microbial assemblages may be better predicted at the functional genes level rather than at taxonomic level. Furthermore, relative metabolic potentials of genes involved in many key ecological functions (for example, nitrogen and phosphate utilization, metals resistance and stress response) were extrapolated to increase under more acidic and metal-rich conditions, indicating a critical strategy of stress adaptation in these extraordinary communities. Collectively, our findings indicate that natural selection rather than geographic distance has a more crucial role in shaping the taxonomic and functional patterns of AMD microbial community that readily predicted by modeling methods and suggest that the model-based approach is essential to better understand natural acidophilic microbial communities.

Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction.

PubMed

Bossi, Flavia; Fan, Jue; Xiao, Jun; Chandra, Lilyana; Shen, Max; Dorone, Yanniv; Wagner, Doris; Rhee, Seung Y

2017-06-26

The molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. To identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation. We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators.

DIANA-microT web server: elucidating microRNA functions through target prediction.

PubMed

Maragkakis, M; Reczko, M; Simossis, V A; Alexiou, P; Papadopoulos, G L; Dalamagas, T; Giannopoulos, G; Goumas, G; Koukis, E; Kourtis, K; Vergoulis, T; Koziris, N; Sellis, T; Tsanakas, P; Hatzigeorgiou, A G

2009-07-01

Computational microRNA (miRNA) target prediction is one of the key means for deciphering the role of miRNAs in development and disease. Here, we present the DIANA-microT web server as the user interface to the DIANA-microT 3.0 miRNA target prediction algorithm. The web server provides extensive information for predicted miRNA:target gene interactions with a user-friendly interface, providing extensive connectivity to online biological resources. Target gene and miRNA functions may be elucidated through automated bibliographic searches and functional information is accessible through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The web server offers links to nomenclature, sequence and protein databases, and users are facilitated by being able to search for targeted genes using different nomenclatures or functional features, such as the genes possible involvement in biological pathways. The target prediction algorithm supports parameters calculated individually for each miRNA:target gene interaction and provides a signal-to-noise ratio and a precision score that helps in the evaluation of the significance of the predicted results. Using a set of miRNA targets recently identified through the pSILAC method, the performance of several computational target prediction programs was assessed. DIANA-microT 3.0 achieved there with 66% the highest ratio of correctly predicted targets over all predicted targets. The DIANA-microT web server is freely available at www.microrna.gr/microT.

The identification of protein domains that mediate functional interactions between Rab-GTPases and RabGAPs using 3D protein modeling.

PubMed

Davie, Jeremiah J; Faitar, Silviu L

2017-01-01

Currently, time-consuming serial in vitro experimentation involving immunocytochemistry or radiolabeled materials is required to identify which of the numerous Rab-GTPases (Rab) and Rab-GTPase activating proteins (RabGAP) are capable of functional interactions. These interactions are essential for numerous cellular functions, and in silico methods of reducing in vitro trial and error would accelerate the pace of research in cell biology. We have utilized a combination of three-dimensional protein modeling and protein bioinformatics to identify domains present in Rab proteins that are predictive of their functional interaction with a specific RabGAP. The RabF2 and RabSF1 domains appear to play functional roles in mediating the interaction between Rabs and RabGAPs. Moreover, the RabSF1 domain can be used to make in silico predictions of functional Rab/RabGAP pairs. This method is expected to be a broadly applicable tool for predicting protein-protein interactions where existing crystal structures for homologs of the proteins of interest are available.

Skill versus luck: A motivational analysis of gambling involvement.

PubMed

Chantal, Y; Vallerand, R J

1996-12-01

The purpose of the present investigation was to test the skill/luck distinction among gambling games by comparing the motivations underlying participation in a skill (horse racing) and a luck (lottery) betting activity. Predictions were made using Self-Determination Theory (Deci & Ryan, 1985, 1991). It was predicted that self-determined motivations (intrinsic motivation and identified regulation) would be more prominent for the skill game because it is conducive to optimal challenges, fun, and self-involvement. Conversely, the non self-determined forms of motivation (especially external regulation) should be more important for the game of luck because the luck dimension precludes true involvement of the self and orients the individual towards material gains. Results from a hierarchical discriminant function analysis, with 120 gamblers predominantly involved in one of the two betting activities, supported these hypotheses. These results highlight the relevance of a motivational analysis for a better understanding of the inherent properties of gambling games.

Value Development Underlies the Benefits of Parents’ Involvement in Children’s Learning: A Longitudinal Investigation in the United States and China

PubMed Central

Cheung, Cecilia Sin-Sze; Pomerantz, Eva M.

2014-01-01

This research examined whether the benefits of parents’ involvement in children’s learning are due in part to value development among children. Four times over the seventh and eighth grades, 825 American and Chinese children (mean age = 12.73 years) reported on their parents’ involvement in their learning and their perceptions of the value their parents place on school achievement as well as the value they themselves place on it. Children’s academic functioning was assessed via children’s reports and school records. Value development partially explained the effects of parents’ involvement on children’s academic functioning in the United States and China. For example, the more children reported their parents as involved, the more they perceived them as placing value on achievement six months later; such perceptions in turn predicted the subsequent value children placed on achievement, which foreshadowed enhanced grades. PMID:25937669

Jenner-predict server: prediction of protein vaccine candidates (PVCs) in bacteria based on host-pathogen interactions

PubMed Central

2013-01-01

Background Subunit vaccines based on recombinant proteins have been effective in preventing infectious diseases and are expected to meet the demands of future vaccine development. Computational approach, especially reverse vaccinology (RV) method has enormous potential for identification of protein vaccine candidates (PVCs) from a proteome. The existing protective antigen prediction software and web servers have low prediction accuracy leading to limited applications for vaccine development. Besides machine learning techniques, those software and web servers have considered only protein’s adhesin-likeliness as criterion for identification of PVCs. Several non-adhesin functional classes of proteins involved in host-pathogen interactions and pathogenesis are known to provide protection against bacterial infections. Therefore, knowledge of bacterial pathogenesis has potential to identify PVCs. Results A web server, Jenner-Predict, has been developed for prediction of PVCs from proteomes of bacterial pathogens. The web server targets host-pathogen interactions and pathogenesis by considering known functional domains from protein classes such as adhesin, virulence, invasin, porin, flagellin, colonization, toxin, choline-binding, penicillin-binding, transferring-binding, fibronectin-binding and solute-binding. It predicts non-cytosolic proteins containing above domains as PVCs. It also provides vaccine potential of PVCs in terms of their possible immunogenicity by comparing with experimentally known IEDB epitopes, absence of autoimmunity and conservation in different strains. Predicted PVCs are prioritized so that only few prospective PVCs could be validated experimentally. The performance of web server was evaluated against known protective antigens from diverse classes of bacteria reported in Protegen database and datasets used for VaxiJen server development. The web server efficiently predicted known vaccine candidates reported from Streptococcus pneumoniae and Escherichia coli proteomes. The Jenner-Predict server outperformed NERVE, Vaxign and VaxiJen methods. It has sensitivity of 0.774 and 0.711 for Protegen and VaxiJen dataset, respectively while specificity of 0.940 has been obtained for the latter dataset. Conclusions Better prediction accuracy of Jenner-Predict web server signifies that domains involved in host-pathogen interactions and pathogenesis are better criteria for prediction of PVCs. The web server has successfully predicted maximum known PVCs belonging to different functional classes. Jenner-Predict server is freely accessible at http://117.211.115.67/vaccine/home.html PMID:23815072

Interactions between the nucleus accumbens and auditory cortices predict music reward value.

PubMed

Salimpoor, Valorie N; van den Bosch, Iris; Kovacevic, Natasa; McIntosh, Anthony Randal; Dagher, Alain; Zatorre, Robert J

2013-04-12

We used functional magnetic resonance imaging to investigate neural processes when music gains reward value the first time it is heard. The degree of activity in the mesolimbic striatal regions, especially the nucleus accumbens, during music listening was the best predictor of the amount listeners were willing to spend on previously unheard music in an auction paradigm. Importantly, the auditory cortices, amygdala, and ventromedial prefrontal regions showed increased activity during listening conditions requiring valuation, but did not predict reward value, which was instead predicted by increasing functional connectivity of these regions with the nucleus accumbens as the reward value increased. Thus, aesthetic rewards arise from the interaction between mesolimbic reward circuitry and cortical networks involved in perceptual analysis and valuation.

ATLAS trigger operations: Upgrades to ``Xmon'' rate prediction system

NASA Astrophysics Data System (ADS)

Myers, Ava; Aukerman, Andrew; Hong, Tae Min; Atlas Collaboration

2017-01-01

We present ``Xmon,'' a tool to monitor trigger rates in the Control Room of the ATLAS Experiment. We discuss Xmon's recent (1) updates, (2) upgrades, and (3) operations. (1) Xmon was updated to modify the tool written for the three-level trigger architecture in Run-1 (2009-2012) to adapt to the new two-level system for Run-2 (2015-current). The tool takes as input the beam luminosity to make a rate prediction, which is compared with incoming rates to detect anomalies that occur both globally throughout a run and locally within a run. Global offsets are more commonly caught by the predictions based upon past runs, where offline processing allows for function adjustments and fit quality through outlier rejection. (2) Xmon was upgraded to detect local offsets using on-the-fly predictions, which uses a sliding window of in-run rates to make predictions. (3) Xmon operations examples are given. Future work involves further automation of the steps to provide the predictive functions and for alerting shifters.

Predicting the practice effects on the blood oxygenation level-dependent (BOLD) function of fMRI in a symbolic manipulation task

NASA Astrophysics Data System (ADS)

Qin, Yulin; Sohn, Myeong-Ho; Anderson, John R.; Stenger, V. Andrew; Fissell, Kate; Goode, Adam; Carter, Cameron S.

2003-04-01

Based on adaptive control of thought-rational (ACT-R), a cognitive architecture for cognitive modeling, researchers have developed an information-processing model to predict the blood oxygenation level-dependent (BOLD) response of functional MRI in symbol manipulation tasks. As an extension of this research, the current event-related functional MRI study investigates the effect of relatively extensive practice on the activation patterns of related brain regions. The task involved performing transformations on equations in an artificial algebra system. This paper shows that the base-level activation learning in the ACT-R theory can predict the change of the BOLD response in practice in a left prefrontal region reflecting retrieval of information. In contrast, practice has relatively little effect on the form of BOLD response in the parietal region reflecting imagined transformations to the equation or the motor region reflecting manual programming.

Functional hierarchy underlies preferential connectivity disturbances in schizophrenia.

PubMed

Yang, Genevieve J; Murray, John D; Wang, Xiao-Jing; Glahn, David C; Pearlson, Godfrey D; Repovs, Grega; Krystal, John H; Anticevic, Alan

2016-01-12

Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia.

Functional hierarchy underlies preferential connectivity disturbances in schizophrenia

PubMed Central

Yang, Genevieve J.; Murray, John D.; Wang, Xiao-Jing; Glahn, David C.; Pearlson, Godfrey D.; Repovs, Grega; Krystal, John H.; Anticevic, Alan

2016-01-01

Schizophrenia may involve an elevated excitation/inhibition (E/I) ratio in cortical microcircuits. It remains unknown how this regulatory disturbance maps onto neuroimaging findings. To address this issue, we implemented E/I perturbations within a neural model of large-scale functional connectivity, which predicted hyperconnectivity following E/I elevation. To test predictions, we examined resting-state functional MRI in 161 schizophrenia patients and 164 healthy subjects. As predicted, patients exhibited elevated functional connectivity that correlated with symptom levels, and was most prominent in association cortices, such as the fronto-parietal control network. This pattern was absent in patients with bipolar disorder (n = 73). To account for the pattern observed in schizophrenia, we integrated neurobiologically plausible, hierarchical differences in association vs. sensory recurrent neuronal dynamics into our model. This in silico architecture revealed preferential vulnerability of association networks to E/I imbalance, which we verified empirically. Reported effects implicate widespread microcircuit E/I imbalance as a parsimonious mechanism for emergent inhomogeneous dysconnectivity in schizophrenia. PMID:26699491

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

Volkow N. D.; Wang G.; Volkow, N.D.

The ability to resist the urge to eat requires the proper functioning of neuronal circuits involved in top-down control to oppose the conditioned responses that predict reward from eating the food and the desire to eat the food. Imaging studies show that obese subjects might have impairments in dopaminergic pathways that regulate neuronal systems associated with reward sensitivity, conditioning and control. It is known that the neuropeptides that regulate energy balance (homeostatic processes) through the hypothalamus also modulate the activity of dopamine cells and their projections into regions involved in the rewarding processes underlying food intake. It is postulated thatmore » this could also be a mechanism by which overeating and the resultant resistance to homoeostatic signals impairs the function of circuits involved in reward sensitivity, conditioning and cognitive control.« less

Electrochemical carbon dioxide concentrator: Math model

NASA Technical Reports Server (NTRS)

Marshall, R. D.; Schubert, F. H.; Carlson, J. N.

1973-01-01

A steady state computer simulation model of an Electrochemical Depolarized Carbon Dioxide Concentrator (EDC) has been developed. The mathematical model combines EDC heat and mass balance equations with empirical correlations derived from experimental data to describe EDC performance as a function of the operating parameters involved. The model is capable of accurately predicting performance over EDC operating ranges. Model simulation results agree with the experimental data obtained over the prediction range.

GalaxyGPCRloop: Template-Based and Ab Initio Structure Sampling of the Extracellular Loops of G-Protein-Coupled Receptors.

PubMed

Won, Jonghun; Lee, Gyu Rie; Park, Hahnbeom; Seok, Chaok

2018-06-07

The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In this study, a new ECL2 conformational sampling method involving both template-based and ab initio sampling was developed. Inspired by the observation of similar ECL2 structures of closely related GPCRs, a template-based sampling method employing loop structure templates selected from the structure database was developed. A new metric for evaluating similarity of the target loop to templates was introduced for template selection. An ab initio loop sampling method was also developed to treat cases without highly similar templates. The ab initio method is based on the previously developed fragment assembly and loop closure method. A new sampling component that takes advantage of secondary structure prediction was added. In addition, a conserved disulfide bridge restraining ECL2 conformation was predicted and analytically incorporated into sampling, reducing the effective dimension of the conformational search space. The sampling method was combined with an existing energy function for comparison with previously reported loop structure prediction methods, and the benchmark test demonstrated outstanding performance.

Diffusion tensor imaging of the corticospinal tract before and after mass resection as correlated with clinical motor findings: preliminary data.

PubMed

Laundre, Bryan J; Jellison, Brian J; Badie, Behnam; Alexander, Andrew L; Field, Aaron S

2005-04-01

The role of diffusion tensor imaging (DTI) in neurosurgical planning and follow-up is currently being defined and needs clinical validation. To that end, we sought correlations between preoperative and postoperative DTI and clinical motor deficits in patients with space-occupying lesions involving the corticospinal tract (CST). DTI findings in four patients with masses near the CST and not involving motor cortex were retrospectively reviewed and compared with contralateral motor strength. CST involvement was determined from anisotropy and eigenvector directional color maps. The CST was considered involved if it was substantially deviated or had decreased anisotropy. Interpretations of the DTIs were blinded to assessments of motor strength, and vice versa. Of the four patients with potential CST involvement before surgery, DTI confirmed CST involvement in three, all of whom had preoperative motor deficits. The patient without CST involvement on DTI had no motor deficit. After surgery, DTI showed CST preservation and normalization of the position and/or anisotropy in two of the three patients with preoperative deficits, and both of those patients had improvement in motor strength. The other patient with preoperative deficits had evidence of wallerian degeneration on DTI and had only equivocal clinical improvement. Preoperative CST involvement, as determined on DTI, was predictive of the presence or absence of motor deficits, and postoperative CST normalization on DTI was predictive of clinical improvement. Further study is warranted to define the role of DTI in planning tumor resections and predicting postoperative motor function.

Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction

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

Bossi, Flavia; Fan, Jue; Xiao, Jun

Here, the molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. As a result, to identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation.more » We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators.« less

Systematic discovery of novel eukaryotic transcriptional regulators using sequence homology independent prediction

DOE PAGES

Bossi, Flavia; Fan, Jue; Xiao, Jun; ...

2017-06-26

Here, the molecular function of a gene is most commonly inferred by sequence similarity. Therefore, genes that lack sufficient sequence similarity to characterized genes (such as certain classes of transcriptional regulators) are difficult to classify using most function prediction algorithms and have remained uncharacterized. As a result, to identify novel transcriptional regulators systematically, we used a feature-based pipeline to screen protein families of unknown function. This method predicted 43 transcriptional regulator families in Arabidopsis thaliana, 7 families in Drosophila melanogaster, and 9 families in Homo sapiens. Literature curation validated 12 of the predicted families to be involved in transcriptional regulation.more » We tested 33 out of the 195 Arabidopsis putative transcriptional regulators for their ability to activate transcription of a reporter gene in planta and found twelve coactivators, five of which had no prior literature support. To investigate mechanisms of action in which the predicted regulators might work, we looked for interactors of an Arabidopsis candidate that did not show transactivation activity in planta and found that it might work with other members of its own family and a subunit of the Polycomb Repressive Complex 2 to regulate transcription. Our results demonstrate the feasibility of assigning molecular function to proteins of unknown function without depending on sequence similarity. In particular, we identified novel transcriptional regulators using biological features enriched in transcription factors. The predictions reported here should accelerate the characterization of novel regulators.« less

Defining the Predicted Protein Secretome of the Fungal Wheat Leaf Pathogen Mycosphaerella graminicola

PubMed Central

Morais do Amaral, Alexandre; Antoniw, John; Rudd, Jason J.; Hammond-Kosack, Kim E.

2012-01-01

The Dothideomycete fungus Mycosphaerella graminicola is the causal agent of Septoria tritici blotch, a devastating disease of wheat leaves that causes dramatic decreases in yield. Infection involves an initial extended period of symptomless intercellular colonisation prior to the development of visible necrotic disease lesions. Previous functional genomics and gene expression profiling studies have implicated the production of secreted virulence effector proteins as key facilitators of the initial symptomless growth phase. In order to identify additional candidate virulence effectors, we re-analysed and catalogued the predicted protein secretome of M. graminicola isolate IPO323, which is currently regarded as the reference strain for this species. We combined several bioinformatic approaches in order to increase the probability of identifying truly secreted proteins with either a predicted enzymatic function or an as yet unknown function. An initial secretome of 970 proteins was predicted, whilst further stringent selection criteria predicted 492 proteins. Of these, 321 possess some functional annotation, the composition of which may reflect the strictly intercellular growth habit of this pathogen, leaving 171 with no functional annotation. This analysis identified a protein family encoding secreted peroxidases/chloroperoxidases (PF01328) which is expanded within all members of the family Mycosphaerellaceae. Further analyses were done on the non-annotated proteins for size and cysteine content (effector protein hallmarks), and then by studying the distribution of homologues in 17 other sequenced Dothideomycete fungi within an overall total of 91 predicted proteomes from fungal, oomycete and nematode species. This detailed M. graminicola secretome analysis provides the basis for further functional and comparative genomics studies. PMID:23236356

Substantia nigra activity level predicts trial-to-trial adjustments in cognitive control

PubMed Central

Boehler, C.N.; Bunzeck, N.; Krebs, R.M.; Noesselt, T.; Schoenfeld, M.A.; Heinze, H.-J.; Münte, T.F.; Woldorff, M.G.; Hopf, J.-M.

2011-01-01

Effective adaptation to the demands of a changing environment requires flexible cognitive control. The medial and lateral frontal cortices are involved in such control processes, putatively in close interplay with the basal ganglia. In particular, dopaminergic projections from the midbrain (i.e., from the substantia nigra (SN) and the ventral tegmental area (VTA)) have been proposed to play a pivotal role in modulating the activity in these areas for cognitive control purposes. In that dopaminergic involvement has been strongly implicated in reinforcement learning, these ideas suggest functional links between reinforcement learning, where the outcome of actions shapes behavior over time, and cognitive control in a more general context, where no direct reward is involved. Here, we provide evidence from functional MRI in humans that activity in the SN predicts systematic subsequent trial-to-trial response time (RT) prolongations that are thought to reflect cognitive control in a Stop-signal paradigm. In particular, variations in the activity level of the SN in one trial predicted the degree of RT prolongation on the subsequent trial, consistent with a modulating output signal from the SN being involved in enhancing cognitive control. This link between SN activity and subsequent behavioral adjustments lends support to theoretical accounts that propose dopaminergic control signals that shape behavior both in the presence and absence of direct reward. This SN-based modulatory mechanism is presumably mediated via a wider network that determines response speed in this task, including frontal and parietal control regions, along with the basal ganglia and the associated subthalamic nucleus. PMID:20465358

Characteristics of genomic signatures derived using univariate methods and mechanistically anchored functional descriptors for predicting drug- and xenobiotic-induced nephrotoxicity.

PubMed

Shi, Weiwei; Bugrim, Andrej; Nikolsky, Yuri; Nikolskya, Tatiana; Brennan, Richard J

2008-01-01

ABSTRACT The ideal toxicity biomarker is composed of the properties of prediction (is detected prior to traditional pathological signs of injury), accuracy (high sensitivity and specificity), and mechanistic relationships to the endpoint measured (biological relevance). Gene expression-based toxicity biomarkers ("signatures") have shown good predictive power and accuracy, but are difficult to interpret biologically. We have compared different statistical methods of feature selection with knowledge-based approaches, using GeneGo's database of canonical pathway maps, to generate gene sets for the classification of renal tubule toxicity. The gene set selection algorithms include four univariate analyses: t-statistics, fold-change, B-statistics, and RankProd, and their combination and overlap for the identification of differentially expressed probes. Enrichment analysis following the results of the four univariate analyses, Hotelling T-square test, and, finally out-of-bag selection, a variant of cross-validation, were used to identify canonical pathway maps-sets of genes coordinately involved in key biological processes-with classification power. Differentially expressed genes identified by the different statistical univariate analyses all generated reasonably performing classifiers of tubule toxicity. Maps identified by enrichment analysis or Hotelling T-square had lower classification power, but highlighted perturbed lipid homeostasis as a common discriminator of nephrotoxic treatments. The out-of-bag method yielded the best functionally integrated classifier. The map "ephrins signaling" performed comparably to a classifier derived using sparse linear programming, a machine learning algorithm, and represents a signaling network specifically involved in renal tubule development and integrity. Such functional descriptors of toxicity promise to better integrate predictive toxicogenomics with mechanistic analysis, facilitating the interpretation and risk assessment of predictive genomic investigations.

Exploiting Amino Acid Composition for Predicting Protein-Protein Interactions

PubMed Central

Roy, Sushmita; Martinez, Diego; Platero, Harriett; Lane, Terran; Werner-Washburne, Margaret

2009-01-01

Background Computational prediction of protein interactions typically use protein domains as classifier features because they capture conserved information of interaction surfaces. However, approaches relying on domains as features cannot be applied to proteins without any domain information. In this paper, we explore the contribution of pure amino acid composition (AAC) for protein interaction prediction. This simple feature, which is based on normalized counts of single or pairs of amino acids, is applicable to proteins from any sequenced organism and can be used to compensate for the lack of domain information. Results AAC performed at par with protein interaction prediction based on domains on three yeast protein interaction datasets. Similar behavior was obtained using different classifiers, indicating that our results are a function of features and not of classifiers. In addition to yeast datasets, AAC performed comparably on worm and fly datasets. Prediction of interactions for the entire yeast proteome identified a large number of novel interactions, the majority of which co-localized or participated in the same processes. Our high confidence interaction network included both well-studied and uncharacterized proteins. Proteins with known function were involved in actin assembly and cell budding. Uncharacterized proteins interacted with proteins involved in reproduction and cell budding, thus providing putative biological roles for the uncharacterized proteins. Conclusion AAC is a simple, yet powerful feature for predicting protein interactions, and can be used alone or in conjunction with protein domains to predict new and validate existing interactions. More importantly, AAC alone performs at par with existing, but more complex, features indicating the presence of sequence-level information that is predictive of interaction, but which is not necessarily restricted to domains. PMID:19936254

Hidden state prediction: a modification of classic ancestral state reconstruction algorithms helps unravel complex symbioses.

PubMed

Zaneveld, Jesse R R; Thurber, Rebecca L V

2014-01-01

Complex symbioses between animal or plant hosts and their associated microbiotas can involve thousands of species and millions of genes. Because of the number of interacting partners, it is often impractical to study all organisms or genes in these host-microbe symbioses individually. Yet new phylogenetic predictive methods can use the wealth of accumulated data on diverse model organisms to make inferences into the properties of less well-studied species and gene families. Predictive functional profiling methods use evolutionary models based on the properties of studied relatives to put bounds on the likely characteristics of an organism or gene that has not yet been studied in detail. These techniques have been applied to predict diverse features of host-associated microbial communities ranging from the enzymatic function of uncharacterized genes to the gene content of uncultured microorganisms. We consider these phylogenetically informed predictive techniques from disparate fields as examples of a general class of algorithms for Hidden State Prediction (HSP), and argue that HSP methods have broad value in predicting organismal traits in a variety of contexts, including the study of complex host-microbe symbioses.

Prediction of jump phenomena in rotationally-coupled maneuvers of aircraft, including nonlinear aerodynamic effects

NASA Technical Reports Server (NTRS)

Young, J. W.; Schy, A. A.; Johnson, K. G.

1977-01-01

An analytical method has been developed for predicting critical control inputs for which nonlinear rotational coupling may cause sudden jumps in aircraft response. The analysis includes the effect of aerodynamics which are nonlinear in angle of attack. The method involves the simultaneous solution of two polynomials in roll rate, whose coefficients are functions of angle of attack and the control inputs. Results obtained using this procedure are compared with calculated time histories to verify the validity of the method for predicting jump-like instabilities.

Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

PubMed

Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

2015-12-01

Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of Viscum album L. miRNAs and prediction of their medicinal values

PubMed Central

Adolf, Jacob; Melzig, Matthias F.

2017-01-01

MicroRNAs (miRNAs) are a class of approximately 22 nucleotides single-stranded non-coding RNA molecules that play crucial roles in gene expression. It has been reported that the plant miRNAs might enter mammalian bloodstream and have a functional role in human metabolism, indicating that miRNAs might be one of the hidden bioactive ingredients in medicinal plants. Viscum album L. (Loranthaceae, European mistletoe) has been widely used for the treatment of cancer and cardiovascular diseases, but its functional compounds have not been well characterized. We considered that miRNAs might be involved in the pharmacological activities of V. album. High-throughput Illumina sequencing was performed to identify the novel and conserved miRNAs of V. album. The putative human targets were predicted. In total, 699 conserved miRNAs and 1373 novel miRNAs have been identified from V. album. Based on the combined use of TargetScan, miRanda, PITA, and RNAhybrid methods, the intersection of 30697 potential human genes have been predicted as putative targets of 29 novel miRNAs, while 14559 putative targets were highly enriched in 33 KEGG pathways. Interestingly, these highly enriched KEGG pathways were associated with some human diseases, especially cancer, cardiovascular diseases and neurological disorders, which might explain the clinical use as well as folk medicine use of mistletoe. However, further experimental validation is necessary to confirm these human targets of mistletoe miRNAs. Additionally, target genes involved in bioactive components synthesis in V. album were predicted as well. A total of 68 miRNAs were predicted to be involved in terpenoid biosynthesis, while two miRNAs including val-miR152 and miR9738 were predicted to target viscotoxins and lectins, respectively, which increased the knowledge regarding miRNA-based regulation of terpenoid biosynthesis, lectin and viscotoxin expressions in V. album. PMID:29112983

Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.

PubMed

Wada, Masayoshi; Takahashi, Hiroki; Altaf-Ul-Amin, Md; Nakamura, Kensuke; Hirai, Masami Y; Ohta, Daisaku; Kanaya, Shigehiko

2012-07-15

Operon-like arrangements of genes occur in eukaryotes ranging from yeasts and filamentous fungi to nematodes, plants, and mammals. In plants, several examples of operon-like gene clusters involved in metabolic pathways have recently been characterized, e.g. the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice. Such operon-like gene clusters are defined by their co-regulation or neighboring positions within immediate vicinity of chromosomal regions. A comprehensive analysis of the expression of neighboring genes therefore accounts a crucial step to reveal the complete set of operon-like gene clusters within a genome. Genome-wide prediction of operon-like gene clusters should contribute to functional annotation efforts and provide novel insight into evolutionary aspects acquiring certain biological functions as well. We predicted co-expressed gene clusters by comparing the Pearson correlation coefficient of neighboring genes and randomly selected gene pairs, based on a statistical method that takes false discovery rate (FDR) into consideration for 1469 microarray gene expression datasets of A. thaliana. We estimated that A. thaliana contains 100 operon-like gene clusters in total. We predicted 34 statistically significant gene clusters consisting of 3 to 22 genes each, based on a stringent FDR threshold of 0.1. Functional relationships among genes in individual clusters were estimated by sequence similarity and functional annotation of genes. Duplicated gene pairs (determined based on BLAST with a cutoff of E<10(-5)) are included in 27 clusters. Five clusters are associated with metabolism, containing P450 genes restricted to the Brassica family and predicted to be involved in secondary metabolism. Operon-like clusters tend to include genes encoding bio-machinery associated with ribosomes, the ubiquitin/proteasome system, secondary metabolic pathways, lipid and fatty-acid metabolism, and the lipid transfer system. Copyright © 2012 Elsevier B.V. All rights reserved.

Hybrid density-functional calculations of phonons in LaCoO3

NASA Astrophysics Data System (ADS)

Gryaznov, Denis; Evarestov, Robert A.; Maier, Joachim

2010-12-01

Phonon frequencies at Γ point in nonmagnetic rhombohedral phase of LaCoO3 were calculated using density-functional theory with hybrid exchange correlation functional PBE0. The calculations involved a comparison of results for two types of basis functions commonly used in ab initio calculations, namely, the plane-wave approach and linear combination of atomic orbitals, as implemented in VASP and CRYSTAL computer codes, respectively. A good qualitative, but also within an error margin of less than 30%, a quantitative agreement was observed not only between the two formalisms but also between theoretical and experimental phonon frequency predictions. Moreover, the correlation between the phonon symmetries in cubic and rhombohedral phases is discussed in detail on the basis of group-theoretical analysis. It is concluded that the hybrid PBE0 functional is able to predict correctly the phonon properties in LaCoO3 .

Understanding the bond-energy, hardness, and adhesive force from the phase diagram via the electron work function

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

Lu, Hao; Huang, Xiaochen; Li, Dongyang, E-mail: dongyang.li@ualberta.ca

2014-11-07

Properties of metallic materials are intrinsically determined by their electron behavior. However, relevant theoretical treatment involving quantum mechanics is complicated and difficult to be applied in materials design. Electron work function (EWF) has been demonstrated to be a simple but fundamental parameter which well correlates properties of materials with their electron behavior and could thus be used to predict material properties from the aspect of electron activities in a relatively easy manner. In this article, we propose a method to extract the electron work functions of binary solid solutions or alloys from their phase diagrams and use this simple approachmore » to predict their mechanical strength and surface properties, such as adhesion. Two alloys, Fe-Ni and Cu-Zn, are used as samples for the study. EWFs extracted from phase diagrams show same trends as experimentally observed ones, based on which hardness and surface adhesive force of the alloys are predicted. This new methodology provides an alternative approach to predict material properties based on the work function, which is extractable from the phase diagram. This work may also help maximize the power of phase diagram for materials design and development.« less

Binding affinity of five PBPs to Ostrinia sex pheromones

USDA-ARS?s Scientific Manuscript database

Pheromone binding proteins (PBPs) of Lepidoptera function in chemical communication, mate attraction and recognition, and may be involved in reinforcement of sexual isolation between recently diverged species. Directional selection was previously predicted between PBP3 orthologs of the corn borer si...

Clinical and electrophysiologic attributes as predictors of results of autonomic function tests

NASA Technical Reports Server (NTRS)

Wu, C. L.; Denq, J. C.; Harper, C. M.; O'Brien, P. C.; Low, P. A.

1998-01-01

Autonomic dysfunction is a feature of some neuropathies and not others. It has been suggested that some clinical and electrophysiologic attributes are predictable of autonomic impairment detected using laboratory testing; however, dear guidelines are unavailable. We evaluated 138 relatively unselected patients with peripheral neuropathy who underwent neurologic evaluation, electromyography (EMG), nerve conduction studies, and autonomic function tests to determine which variables were predictive of laboratory findings of autonomic failure. The variables evaluated were 1) clinical somatic neuropathic findings, 2) clinical autonomic symptoms, and 3) electrophysiologic findings. Autonomic symptoms were strongly predictive (Rs = 0.40, p < 0.001) of autonomic failure. Among the non-autonomic indices, absent ankle reflexes were mildly predictive (Rs = 0.19, p = 0.022) of autonomic impairment, but all others were not (duration, clinical pattern, severity, weakness, sensory loss). Electrophysiologic changes of an axonal neuropathy predicted autonomic impairment while demyelinating neuropathy did not. We conclude that autonomic studies will most likely be abnormal in patients who have symptoms of autonomic involvement and those who have an axonal neuropathy.

Prediction-Correction Algorithms for Time-Varying Constrained Optimization

DOE PAGES

Simonetto, Andrea; Dall'Anese, Emiliano

2017-07-26

This article develops online algorithms to track solutions of time-varying constrained optimization problems. Particularly, resembling workhorse Kalman filtering-based approaches for dynamical systems, the proposed methods involve prediction-correction steps to provably track the trajectory of the optimal solutions of time-varying convex problems. The merits of existing prediction-correction methods have been shown for unconstrained problems and for setups where computing the inverse of the Hessian of the cost function is computationally affordable. This paper addresses the limitations of existing methods by tackling constrained problems and by designing first-order prediction steps that rely on the Hessian of the cost function (and do notmore » require the computation of its inverse). In addition, the proposed methods are shown to improve the convergence speed of existing prediction-correction methods when applied to unconstrained problems. Numerical simulations corroborate the analytical results and showcase performance and benefits of the proposed algorithms. A realistic application of the proposed method to real-time control of energy resources is presented.« less

Combining Machine Learning Systems and Multiple Docking Simulation Packages to Improve Docking Prediction Reliability for Network Pharmacology

PubMed Central

Hsin, Kun-Yi; Ghosh, Samik; Kitano, Hiroaki

2013-01-01

Increased availability of bioinformatics resources is creating opportunities for the application of network pharmacology to predict drug effects and toxicity resulting from multi-target interactions. Here we present a high-precision computational prediction approach that combines two elaborately built machine learning systems and multiple molecular docking tools to assess binding potentials of a test compound against proteins involved in a complex molecular network. One of the two machine learning systems is a re-scoring function to evaluate binding modes generated by docking tools. The second is a binding mode selection function to identify the most predictive binding mode. Results from a series of benchmark validations and a case study show that this approach surpasses the prediction reliability of other techniques and that it also identifies either primary or off-targets of kinase inhibitors. Integrating this approach with molecular network maps makes it possible to address drug safety issues by comprehensively investigating network-dependent effects of a drug or drug candidate. PMID:24391846

Social inclusion and its interrelationships with social cognition and social functioning in first-episode psychosis.

PubMed

Gardner, Andrew; Cotton, Sue M; Allott, Kelly; Filia, Kate M; Hester, Robert; Killackey, Eóin

2017-10-27

People with psychosis are at risk of social exclusion. Research is needed in this area due to the lack of direct measurement of social inclusion, which becomes salient in adolescence and is relevant to first-episode psychosis (FEP; the onset of which typically occurs during or shortly after adolescence). Social inclusion may be impacted by impaired social cognition and social functioning, which are related features observed in psychosis. The aim of this study was to explore interrelationship(s) between social cognition, social functioning and social inclusion in FEP while controlling for symptomatology (positive, negative and depressive symptoms) and demographic characteristics. A series of cross-sectional hierarchical multiple regressions were conducted to examine whether: social cognition (theory of mind, emotion recognition) predicted social functioning; social functioning predicted social inclusion, and whether social functioning mediated the relationship between social cognition and social inclusion in people aged 15 to 25 (M = 20.49, SD = 2.41) with FEP (N = 146). Age, sex, premorbid IQ, positive and negative psychotic symptoms and depression were control variables. Poor facial emotion recognition (β = -.22, P < .05) and negative symptoms (β = -.45, P < .001) predicted lower social functioning. Role-specific social functioning (ie, current employment) predicted greater social inclusion (β = .17, P < .05). Higher depression symptomatology predicted lower social inclusion (β = -.43, P < .001). Social functioning did not mediate the relationship between social cognition and inclusion. Psychotic symptoms were unrelated to social inclusion. Employment and depression may influence social inclusion somewhat independently of psychotic symptomatology in FEP. Inferences should be viewed with caution given this study did not involve longitudinal data. © 2017 John Wiley & Sons Australia, Ltd.

Planning versus action: Different decision-making processes predict plans to change one's diet versus actual dietary behavior.

PubMed

Kiviniemi, Marc T; Brown-Kramer, Carolyn R

2015-05-01

Most health decision-making models posit that deciding to engage in a health behavior involves forming a behavioral intention which then leads to actual behavior. However, behavioral intentions and actual behavior may not be functionally equivalent. Two studies examined whether decision-making factors predicting dietary behaviors were the same as or distinct from those predicting intentions. Actual dietary behavior was proximally predicted by affective associations with the behavior. By contrast, behavioral intentions were predicted by cognitive beliefs about behaviors, with no contribution of affective associations. This dissociation has implications for understanding individual regulation of health behaviors and for behavior change interventions. © The Author(s) 2015.

SChloro: directing Viridiplantae proteins to six chloroplastic sub-compartments.

PubMed

Savojardo, Castrense; Martelli, Pier Luigi; Fariselli, Piero; Casadio, Rita

2017-02-01

Chloroplasts are organelles found in plants and involved in several important cell processes. Similarly to other compartments in the cell, chloroplasts have an internal structure comprising several sub-compartments, where different proteins are targeted to perform their functions. Given the relation between protein function and localization, the availability of effective computational tools to predict protein sub-organelle localizations is crucial for large-scale functional studies. In this paper we present SChloro, a novel machine-learning approach to predict protein sub-chloroplastic localization, based on targeting signal detection and membrane protein information. The proposed approach performs multi-label predictions discriminating six chloroplastic sub-compartments that include inner membrane, outer membrane, stroma, thylakoid lumen, plastoglobule and thylakoid membrane. In comparative benchmarks, the proposed method outperforms current state-of-the-art methods in both single- and multi-compartment predictions, with an overall multi-label accuracy of 74%. The results demonstrate the relevance of the approach that is eligible as a good candidate for integration into more general large-scale annotation pipelines of protein subcellular localization. The method is available as web server at http://schloro.biocomp.unibo.it gigi@biocomp.unibo.it.

Two distinct forms of functional lateralization in the human brain

PubMed Central

Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

2013-01-01

The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

Annotation of gene function in citrus using gene expression information and co-expression networks

PubMed Central

2014-01-01

Background The genus Citrus encompasses major cultivated plants such as sweet orange, mandarin, lemon and grapefruit, among the world’s most economically important fruit crops. With increasing volumes of transcriptomics data available for these species, Gene Co-expression Network (GCN) analysis is a viable option for predicting gene function at a genome-wide scale. GCN analysis is based on a “guilt-by-association” principle whereby genes encoding proteins involved in similar and/or related biological processes may exhibit similar expression patterns across diverse sets of experimental conditions. While bioinformatics resources such as GCN analysis are widely available for efficient gene function prediction in model plant species including Arabidopsis, soybean and rice, in citrus these tools are not yet developed. Results We have constructed a comprehensive GCN for citrus inferred from 297 publicly available Affymetrix Genechip Citrus Genome microarray datasets, providing gene co-expression relationships at a genome-wide scale (33,000 transcripts). The comprehensive citrus GCN consists of a global GCN (condition-independent) and four condition-dependent GCNs that survey the sweet orange species only, all citrus fruit tissues, all citrus leaf tissues, or stress-exposed plants. All of these GCNs are clustered using genome-wide, gene-centric (guide) and graph clustering algorithms for flexibility of gene function prediction. For each putative cluster, gene ontology (GO) enrichment and gene expression specificity analyses were performed to enhance gene function, expression and regulation pattern prediction. The guide-gene approach was used to infer novel roles of genes involved in disease susceptibility and vitamin C metabolism, and graph-clustering approaches were used to investigate isoprenoid/phenylpropanoid metabolism in citrus peel, and citric acid catabolism via the GABA shunt in citrus fruit. Conclusions Integration of citrus gene co-expression networks, functional enrichment analysis and gene expression information provide opportunities to infer gene function in citrus. We present a publicly accessible tool, Network Inference for Citrus Co-Expression (NICCE, http://citrus.adelaide.edu.au/nicce/home.aspx), for the gene co-expression analysis in citrus. PMID:25023870

Systematic Prediction of Scaffold Proteins Reveals New Design Principles in Scaffold-Mediated Signal Transduction

PubMed Central

Hu, Jianfei; Neiswinger, Johnathan; Zhang, Jin; Zhu, Heng; Qian, Jiang

2015-01-01

Scaffold proteins play a crucial role in facilitating signal transduction in eukaryotes by bringing together multiple signaling components. In this study, we performed a systematic analysis of scaffold proteins in signal transduction by integrating protein-protein interaction and kinase-substrate relationship networks. We predicted 212 scaffold proteins that are involved in 605 distinct signaling pathways. The computational prediction was validated using a protein microarray-based approach. The predicted scaffold proteins showed several interesting characteristics, as we expected from the functionality of scaffold proteins. We found that the scaffold proteins are likely to interact with each other, which is consistent with previous finding that scaffold proteins tend to form homodimers and heterodimers. Interestingly, a single scaffold protein can be involved in multiple signaling pathways by interacting with other scaffold protein partners. Furthermore, we propose two possible regulatory mechanisms by which the activity of scaffold proteins is coordinated with their associated pathways through phosphorylation process. PMID:26393507

BMI, HOMA-IR, and Fasting Blood Glucose Are Significant Predictors of Peripheral Nerve Dysfunction in Adult Overweight and Obese Nondiabetic Nepalese Individuals: A Study from Central Nepal.

PubMed

Thapa, Lekhjung; Rana, P V S

2016-01-01

Objective. Nondiabetic obese individuals have subclinical involvement of peripheral nerves. We report the factors predicting peripheral nerve function in overweight and obese nondiabetic Nepalese individuals. Methodology. In this cross-sectional study, we included 50 adult overweight and obese nondiabetic volunteers without features of peripheral neuropathy and 50 healthy volunteers to determine the normative nerve conduction data. In cases of abnormal function, the study population was classified on the basis of the number of nerves involved, namely, "<2" or "≥2." Multivariable logistic regression analysis was carried out to predict outcomes. Results. Fasting blood glucose (FBG) was the significant predictor of motor nerve dysfunction (P = 0.039, 95% confidence interval (CI) = 1.003-1.127). Homeostatic model assessment of insulin resistance (HOMA-IR) was the significant predictor (P = 0.019, 96% CI = 1.420-49.322) of sensory nerve dysfunction. Body mass index (BMI) was the significant predictor (P = 0.034, 95% CI = 1.018-1.577) in case of ≥2 mixed nerves' involvement. Conclusion. FBG, HOMA-IR, and BMI were significant predictors of peripheral nerve dysfunction in overweight and obese Nepalese individuals.

Experimental investigation of alternative transmission functions: Quantitative evidence for the importance of nonlinear transmission dynamics in host-parasite systems.

PubMed

Orlofske, Sarah A; Flaxman, Samuel M; Joseph, Maxwell B; Fenton, Andy; Melbourne, Brett A; Johnson, Pieter T J

2018-05-01

Understanding pathogen transmission is crucial for predicting and managing disease. Nonetheless, experimental comparisons of alternative functional forms of transmission remain rare, and those experiments that are conducted are often not designed to test the full range of possible forms. To differentiate among 10 candidate transmission functions, we used a novel experimental design in which we independently varied four factors-duration of exposure, numbers of parasites, numbers of hosts and parasite density-in laboratory infection experiments. We used interactions between amphibian hosts and trematode parasites as a model system and all candidate models incorporated parasite depletion. An additional manipulation involving anaesthesia addressed the effects of host behaviour on transmission form. Across all experiments, nonlinear transmission forms involving either a power law or a negative binomial function were the best-fitting models and consistently outperformed the linear density-dependent and density-independent functions. By testing previously published data for two other host-macroparasite systems, we also found support for the same nonlinear transmission forms. Although manipulations of parasite density are common in transmission studies, the comprehensive set of variables tested in our experiments revealed that variation in density alone was least likely to differentiate among competing transmission functions. Across host-pathogen systems, nonlinear functions may often more accurately represent transmission dynamics and thus provide more realistic predictions for infection. © 2017 The Authors. Journal of Animal Ecology published by John Wiley & Sons Ltd on behalf of British Ecological Society.

Genome-Wide Prediction and Analysis of 3D-Domain Swapped Proteins in the Human Genome from Sequence Information.

PubMed

Upadhyay, Atul Kumar; Sowdhamini, Ramanathan

2016-01-01

3D-domain swapping is one of the mechanisms of protein oligomerization and the proteins exhibiting this phenomenon have many biological functions. These proteins, which undergo domain swapping, have acquired much attention owing to their involvement in human diseases, such as conformational diseases, amyloidosis, serpinopathies, proteionopathies etc. Early realisation of proteins in the whole human genome that retain tendency to domain swap will enable many aspects of disease control management. Predictive models were developed by using machine learning approaches with an average accuracy of 78% (85.6% of sensitivity, 87.5% of specificity and an MCC value of 0.72) to predict putative domain swapping in protein sequences. These models were applied to many complete genomes with special emphasis on the human genome. Nearly 44% of the protein sequences in the human genome were predicted positive for domain swapping. Enrichment analysis was performed on the positively predicted sequences from human genome for their domain distribution, disease association and functional importance based on Gene Ontology (GO). Enrichment analysis was also performed to infer a better understanding of the functional importance of these sequences. Finally, we developed hinge region prediction, in the given putative domain swapped sequence, by using important physicochemical properties of amino acids.

Taxonomic and functional characteristics of microbial communities and their correlation with physicochemical properties of four geothermal springs in Odisha, India

PubMed Central

Badhai, Jhasketan; Ghosh, Tarini S.; Das, Subrata K.

2015-01-01

This study describes microbial diversity in four tropical hot springs representing moderately thermophilic environments (temperature range: 40–58°C; pH: 7.2–7.4) with discrete geochemistry. Metagenome sequence data showed a dominance of Bacteria over Archaea; the most abundant phyla were Chloroflexi and Proteobacteria, although other phyla were also present, such as Acetothermia, Nitrospirae, Acidobacteria, Firmicutes, Deinococcus-Thermus, Bacteroidetes, Thermotogae, Euryarchaeota, Verrucomicrobia, Ignavibacteriae, Cyanobacteria, Actinobacteria, Planctomycetes, Spirochaetes, Armatimonadetes, Crenarchaeota, and Aquificae. The distribution of major genera and their statistical correlation analyses with the physicochemical parameters predicted that the temperature, aqueous concentrations of ions (such as sodium, chloride, sulfate, and bicarbonate), total hardness, dissolved solids and conductivity were the main environmental variables influencing microbial community composition and diversity. Despite the observed high taxonomic diversity, there were only little variations in the overall functional profiles of the microbial communities in the four springs. Genes involved in the metabolism of carbohydrates and carbon fixation were the most abundant functional class of genes present in these hot springs. The distribution of genes involved in carbon fixation predicted the presence of all the six known autotrophic pathways in the metagenomes. A high prevalence of genes involved in membrane transport, signal transduction, stress response, bacterial chemotaxis, and flagellar assembly were observed along with genes involved in the pathways of xenobiotic degradation and metabolism. The analysis of the metagenomic sequences affiliated to the candidate phylum Acetothermia from spring TB-3 provided new insight into the metabolism and physiology of yet-unknown members of this lineage of bacteria. PMID:26579081

Taxonomic and functional characteristics of microbial communities and their correlation with physicochemical properties of four geothermal springs in Odisha, India.

PubMed

Badhai, Jhasketan; Ghosh, Tarini S; Das, Subrata K

2015-01-01

This study describes microbial diversity in four tropical hot springs representing moderately thermophilic environments (temperature range: 40-58°C; pH: 7.2-7.4) with discrete geochemistry. Metagenome sequence data showed a dominance of Bacteria over Archaea; the most abundant phyla were Chloroflexi and Proteobacteria, although other phyla were also present, such as Acetothermia, Nitrospirae, Acidobacteria, Firmicutes, Deinococcus-Thermus, Bacteroidetes, Thermotogae, Euryarchaeota, Verrucomicrobia, Ignavibacteriae, Cyanobacteria, Actinobacteria, Planctomycetes, Spirochaetes, Armatimonadetes, Crenarchaeota, and Aquificae. The distribution of major genera and their statistical correlation analyses with the physicochemical parameters predicted that the temperature, aqueous concentrations of ions (such as sodium, chloride, sulfate, and bicarbonate), total hardness, dissolved solids and conductivity were the main environmental variables influencing microbial community composition and diversity. Despite the observed high taxonomic diversity, there were only little variations in the overall functional profiles of the microbial communities in the four springs. Genes involved in the metabolism of carbohydrates and carbon fixation were the most abundant functional class of genes present in these hot springs. The distribution of genes involved in carbon fixation predicted the presence of all the six known autotrophic pathways in the metagenomes. A high prevalence of genes involved in membrane transport, signal transduction, stress response, bacterial chemotaxis, and flagellar assembly were observed along with genes involved in the pathways of xenobiotic degradation and metabolism. The analysis of the metagenomic sequences affiliated to the candidate phylum Acetothermia from spring TB-3 provided new insight into the metabolism and physiology of yet-unknown members of this lineage of bacteria.

Response of Functional Structure of Soil Microbial Community to Multi-level Nitrogen Additions on the Central Tibetan Plateau

NASA Astrophysics Data System (ADS)

Zhang, G.; Yuan, Y.

2015-12-01

The use of fossil fuels and fertilizers has increased the amount of biologically reactive nitrogen in the atmosphere over the past century. Tibet is the one of the most threatened regions by nitrogen deposition, thus understanding how its microbial communities function maybe of high importance to predicting microbial responses to nitrogen deposition. Here we describe a short-time nitrogen addition conducted in an alpine steppe ecosystem to investigate the response of functional structure of soil microbial community to multi-level nitrogen addition. Using a GeoChip 4.0, we showed that functional diversities and richness of functional genes were unchanged at low level of nitrogen fertilizer inputs (<20 kg N ha-1 yr-1), but significantly decreased at higher nitrogen fertilizer inputs (>=40 kg N ha-1 yr-1). Detrended correspondence analysis indicated that the functional structure of microbial communities was markedly different across the nitrogen gradients. Most C degradation genes whose abundances significantly increased under elevated N fertilizer were those involved in the degradation of relatively labile C (starch, hemicellulose, cellulose), whereas the abundance of certain genes involved in the degradation of recalcitrant C (i.e. lignin) was largely decreased (such as manganese peroxidase, mnp). The results suggest that the elevated N fertilization rates might significantly accelerate the labile C degradation, but might not spur recalcitrant C degradation. The combined effect of gdh and ureC genes involved in N cycling appeared to shift the balance between ammonia and organic N toward organic N ammonification and hence increased the N mineralization potential. Moreover, Urease directly involved in urea mineralization significantly increased. Lastly, Canonical correspondence analysis showed that soil (TOC+NH4++NO3-+NO2-+pH) and plant (Aboveground plant productivity + Shannon Diversity) variables could explain 38.9% of the variation of soil microbial community composition. On the basis of above observations, we predict that increasing of nitrogen deposition on the Tibetan steppe ecosystem is very likely to change soil microbial community functional structure, with particular effects on microbial C and N-cycling genes and consequently microbe-mediated soil C and N dynamics.

Generalized role for the cerebellum in encoding internal models: evidence from semantic processing.

PubMed

Moberget, Torgeir; Gullesen, Eva Hilland; Andersson, Stein; Ivry, Richard B; Endestad, Tor

2014-02-19

The striking homogeneity of cerebellar microanatomy is strongly suggestive of a corresponding uniformity of function. Consequently, theoretical models of the cerebellum's role in motor control should offer important clues regarding cerebellar contributions to cognition. One such influential theory holds that the cerebellum encodes internal models, neural representations of the context-specific dynamic properties of an object, to facilitate predictive control when manipulating the object. The present study examined whether this theoretical construct can shed light on the contribution of the cerebellum to language processing. We reasoned that the cerebellum might perform a similar coordinative function when the context provided by the initial part of a sentence can be highly predictive of the end of the sentence. Using functional MRI in humans we tested two predictions derived from this hypothesis, building on previous neuroimaging studies of internal models in motor control. First, focal cerebellar activation-reflecting the operation of acquired internal models-should be enhanced when the linguistic context leads terminal words to be predictable. Second, more widespread activation should be observed when such predictions are violated, reflecting the processing of error signals that can be used to update internal models. Both predictions were confirmed, with predictability and prediction violations associated with increased blood oxygenation level-dependent signal in the posterior cerebellum (Crus I/II). Our results provide further evidence for cerebellar involvement in predictive language processing and suggest that the notion of cerebellar internal models may be extended to the language domain.

Simple Math is Enough: Two Examples of Inferring Functional Associations from Genomic Data

NASA Technical Reports Server (NTRS)

Liang, Shoudan

2003-01-01

Non-random features in the genomic data are usually biologically meaningful. The key is to choose the feature well. Having a p-value based score prioritizes the findings. If two proteins share a unusually large number of common interaction partners, they tend to be involved in the same biological process. We used this finding to predict the functions of 81 un-annotated proteins in yeast.

A longitudinal examination of coach and peer motivational climates in youth sport: implications for moral attitudes, well-being, and behavioral investment.

PubMed

Ntoumanis, Nikos; Taylor, Ian M; Thøgersen-Ntoumani, Cecilie

2012-01-01

Embedded in achievement goal theory (Ames, 1992; Meece, Anderman, & Anderman, 2006), this study examined how perceptions of coach and peer motivational climate in youth sport predicted moral attitudes, emotional well-being, and indices of behavioral investment in a sample of British adolescents competing in regional leagues. We adopted a longitudinal perspective, taking measures at the middle and the end of a sport season, as well as at the beginning of the following season. Multilevel modeling analyses showed that perceptions of task-involving peer and coach climates were predictive of more adaptive outcomes than were perceptions of ego-involving peer and coach climates. Predictive effects differed as a function of time and outcome variable under investigation. The results indicate the importance of considering peer influence in addition to coach influence when examining motivational climate in youth sport.

Quantitative prediction of solvation free energy in octanol of organic compounds.

PubMed

Delgado, Eduardo J; Jaña, Gonzalo A

2009-03-01

The free energy of solvation, DeltaGS0, in octanol of organic compounds is quantitatively predicted from the molecular structure. The model, involving only three molecular descriptors, is obtained by multiple linear regression analysis from a data set of 147 compounds containing diverse organic functions, namely, halogenated and non-halogenated alkanes, alkenes, alkynes, aromatics, alcohols, aldehydes, ketones, amines, ethers and esters; covering a DeltaGS0 range from about -50 to 0 kJ.mol(-1). The model predicts the free energy of solvation with a squared correlation coefficient of 0.93 and a standard deviation, 2.4 kJ.mol(-1), just marginally larger than the generally accepted value of experimental uncertainty. The involved molecular descriptors have definite physical meaning corresponding to the different intermolecular interactions occurring in the bulk liquid phase. The model is validated with an external set of 36 compounds not included in the training set.

Quantitative Prediction of Solvation Free Energy in Octanol of Organic Compounds

PubMed Central

Delgado, Eduardo J.; Jaña, Gonzalo A.

2009-01-01

The free energy of solvation, ΔGS0, in octanol of organic compunds is quantitatively predicted from the molecular structure. The model, involving only three molecular descriptors, is obtained by multiple linear regression analysis from a data set of 147 compounds containing diverse organic functions, namely, halogenated and non-halogenated alkanes, alkenes, alkynes, aromatics, alcohols, aldehydes, ketones, amines, ethers and esters; covering a ΔGS0 range from about −50 to 0 kJ·mol−1. The model predicts the free energy of solvation with a squared correlation coefficient of 0.93 and a standard deviation, 2.4 kJ·mol−1, just marginally larger than the generally accepted value of experimental uncertainty. The involved molecular descriptors have definite physical meaning corresponding to the different intermolecular interactions occurring in the bulk liquid phase. The model is validated with an external set of 36 compounds not included in the training set. PMID:19399236

Neuropsychological and structural brain lesions in multiple sclerosis: a regional analysis.

PubMed

Swirsky-Sacchetti, T; Mitchell, D R; Seward, J; Gonzales, C; Lublin, F; Knobler, R; Field, H L

1992-07-01

Quantified lesion scores derived from MRI correlate significantly with neuropsychological testing in patients with multiple sclerosis (MS). Variables used to reflect disease severity include total lesion area (TLA), ventricular-brain ratio, and size of the corpus callosum. We used these general measures of cerebral lesion involvement as well as specific ratings of lesion involvement by frontal, temporal, and parieto-occipital regions to quantify the topographic distribution of lesions and consequent effects upon cognitive function. Lesions were heavily distributed in the parieto-occipital regions bilaterally. Neuropsychological tests were highly related to all generalized measures of cerebral involvement, with TLA being the best predictor of neuropsychological deficit. Mean TLA for the cognitively impaired group was 28.30 cm2 versus 7.41 cm2 for the cognitively intact group (p less than 0.0001). Multiple regression analyses revealed that left frontal lobe involvement best predicted impaired abstract problem solving, memory, and word fluency. Left parieto-occipital lesion involvement best predicted deficits in verbal learning and complex visual-integrative skills. Analysis of regional cerebral lesion load may assist in understanding the particular pattern and course of cognitive deficits in MS.

Towards A Predictive First Principles Understanding Of Molecular Adsorption On Graphene

DTIC Science & Technology

2016-10-05

used and developed state-of-the-art quantum mechanical methods to make accurate predictions about the interaction strength and adsorption structure...density functional theory, ab initio methods 16.  SECURITY CLASSIFICATION OF: 17.  LIMITATION OF ABSTRACT SAR 18.  NUMBER OF PAGES   11   19a.  NAME OF...important physical properties for a whole class of systems with weak non-covalent interactions, for example those involving the binding between water

Emotion suppression moderates the quadratic association between RSA and executive function

PubMed Central

Spangler, Derek P.; Bell, Martha Ann; Deater-Deckard, Kirby

2016-01-01

There is uncertainty about whether respiratory sinus arrhythmia (RSA), a cardiac marker of adaptive emotion regulation, is involved in relatively low or high executive function performance. In the present study, we investigated: (1) whether RSA during rest and tasks predict both relatively low and high executive function within a larger quadratic association among the two variables, and (2) the extent to which this quadratic trend was moderated by individual differences in emotion regulation. To achieve these aims, a sample of ethnically and socioeconomically diverse women self-reported reappraisal and emotion suppression. They next experienced a two-minute resting period during which ECG was continually assessed. In the next phase, the women completed an array of executive function and non-executive cognitive tasks while ECG was measured throughout. As anticipated, resting RSA showed a quadratic association with executive function that was strongest for high suppression. These results suggest that relatively high resting RSA may predict poor executive function ability when emotion regulation consumes executive control resources needed for ongoing cognitive performance. PMID:26018941

Impact of mutations on the allosteric conformational equilibrium

PubMed Central

Weinkam, Patrick; Chen, Yao Chi; Pons, Jaume; Sali, Andrej

2012-01-01

Allostery in a protein involves effector binding at an allosteric site that changes the structure and/or dynamics at a distant, functional site. In addition to the chemical equilibrium of ligand binding, allostery involves a conformational equilibrium between one protein substate that binds the effector and a second substate that less strongly binds the effector. We run molecular dynamics simulations using simple, smooth energy landscapes to sample specific ligand-induced conformational transitions, as defined by the effector-bound and unbound protein structures. These simulations can be performed using our web server: http://salilab.org/allosmod/. We then develop a set of features to analyze the simulations and capture the relevant thermodynamic properties of the allosteric conformational equilibrium. These features are based on molecular mechanics energy functions, stereochemical effects, and structural/dynamic coupling between sites. Using a machine-learning algorithm on a dataset of 10 proteins and 179 mutations, we predict both the magnitude and sign of the allosteric conformational equilibrium shift by the mutation; the impact of a large identifiable fraction of the mutations can be predicted with an average unsigned error of 1 kBT. With similar accuracy, we predict the mutation effects for an 11th protein that was omitted from the initial training and testing of the machine-learning algorithm. We also assess which calculated thermodynamic properties contribute most to the accuracy of the prediction. PMID:23228330

Parietal control network activation during memory tasks may be associated with the co-occurrence of externally and internally directed cognition: A cross-function meta-analysis.

PubMed

Kim, Hongkeun

2018-03-15

Functional neuroimaging studies on episodic memory retrieval consistently indicated the activation of the precuneus (PCU), mid-cingulate cortex (MCC), and lateral intraparietal sulcus (latIPS) regions. Although studies typically interpreted these activations in terms of memory retrieval processes, resting-state functional connectivity data indicate that these regions are part of the frontoparietal control network, suggesting a more general, cross-functional role. In this regard, this study proposes a novel hypothesis which suggests that the parietal control network plays a strong role in accommodating the co-occurrence of externally directed cognition (EDC) and internally directed cognition (IDC), which are typically antagonistic to each other. To evaluate how well this dual cognitive processes hypothesis can account for parietal activation patterns during memory tasks, this study provides a cross-function meta-analysis involving 3 different memory paradigms, namely, retrieval success (hit > correct rejection), repetition enhancement (repeated > novel), and subsequent forgetting (forgotten > remembered). Common to these paradigms is that the target condition may involve both EDC (stimulus processing and motor responding) and IDC (intentional remembering, involuntary awareness of previous encounter, or task-unrelated thoughts) strongly, whereas the reference condition may involve EDC to a greater extent, but IDC to a lesser extent. Thus, the dual cognitive processes hypothesis predicts that each of these paradigms will activate similar, overlapping PCU, MCC, and latIPS regions. The results were fully consistent with the prediction, supporting the dual cognitive processes hypothesis. Evidence from relevant prior studies suggests that the dual cognitive processes hypothesis may also apply to non-memory domain tasks. Copyright © 2018 Elsevier B.V. All rights reserved.

LncRNA and mRNA expression profiles of glioblastoma multiforme (GBM) reveal the potential roles of lncRNAs in GBM pathogenesis.

PubMed

Li, Qi; Jia, Hongmei; Li, Haowen; Dong, Chengya; Wang, Yajie; Zou, Zhongmei

2016-11-01

Glioblastoma multiforme (GBM) is the most common brain malignancy. Long non-coding RNAs (lncRNAs) are aberrantly expressed in many cancers and are involved in their cell proliferation, apoptosis, angiogenesis, and invasion. The functional roles of lncRNAs in GBM are less known. We analyzed a cohort of exon microarray datasets from The Cancer Genome Atlas. The differently expressed lncRNAs and mRNA were subjected to construct lncRNA-mRNA co-expression network. Probable functions for lncRNAs were predicted according to lncRNA-mRNA network and genomic adjacency by GO and pathway analysis. The expression of lncRNAs and mRNAs in GBM tissues versus normal brain tissues was examined by quantitative reverse transcription polymerase chain reaction. The 398 lncRNAs and 1995 mRNAs were identified as distinctively expressed in GBM. Probable functional roles for 98 lncRNAs were involved in 30 pathways and 32 gene functions related to tumorigenesis, development, and metastasis. The identified sets of key lncRNAs specific to GBM were subsequently verified by experiment in GBM tissues. Our reports predict the biological functions of a multitude of lncRNAs in GBM that could be potential diagnostic and prognostic biomarkers as well as therapeutic targets. Moreover, our research provides a road map for the identification and analysis of lncRNAs in tumors.

Interplay Between Conceptual Expectations and Movement Predictions Underlies Action Understanding.

PubMed

Ondobaka, Sasha; de Lange, Floris P; Wittmann, Marco; Frith, Chris D; Bekkering, Harold

2015-09-01

Recent accounts of understanding goal-directed action underline the importance of a hierarchical predictive architecture. However, the neural implementation of such an architecture remains elusive. In the present study, we used functional neuroimaging to quantify brain activity associated with predicting physical movements, as they were modulated by conceptual-expectations regarding the purpose of the object involved in the action. Participants observed object-related actions preceded by a cue that generated both conceptual goal expectations and movement goal predictions. In 2 tasks, observers judged whether conceptual or movement goals matched or mismatched the cue. At the conceptual level, expected goals specifically recruited the posterior cingulate cortex, irrespectively of the task and the perceived movement goal. At the movement level, neural activation of the parieto-frontal circuit, including inferior frontal gyrus and the inferior parietal lobe, reflected unpredicted movement goals. Crucially, this movement prediction error was only present when the purpose of the involved object was expected. These findings provide neural evidence that prior conceptual expectations influence processing of physical movement goals and thereby support the hierarchical predictive account of action processing. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A Multigroup Method for the Calculation of Neutron Fluence with a Source Term

NASA Technical Reports Server (NTRS)

Heinbockel, J. H.; Clowdsley, M. S.

1998-01-01

Current research on the Grant involves the development of a multigroup method for the calculation of low energy evaporation neutron fluences associated with the Boltzmann equation. This research will enable one to predict radiation exposure under a variety of circumstances. Knowledge of radiation exposure in a free-space environment is a necessity for space travel, high altitude space planes and satellite design. This is because certain radiation environments can cause damage to biological and electronic systems involving both short term and long term effects. By having apriori knowledge of the environment one can use prediction techniques to estimate radiation damage to such systems. Appropriate shielding can be designed to protect both humans and electronic systems that are exposed to a known radiation environment. This is the goal of the current research efforts involving the multi-group method and the Green's function approach.

Cerebellar tDCS Modulates Neural Circuits during Semantic Prediction: A Combined tDCS-fMRI Study.

PubMed

D'Mello, Anila M; Turkeltaub, Peter E; Stoodley, Catherine J

2017-02-08

It has been proposed that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. In language, semantic prediction speeds speech production and comprehension. Right cerebellar lobules VI and VII (including Crus I/II) are engaged during a variety of language processes and are functionally connected with cerebral cortical language networks. Further, right posterolateral cerebellar neuromodulation modifies behavior during predictive language processing. These data are consistent with a role for the cerebellum in semantic processing and semantic prediction. We combined transcranial direct current stimulation (tDCS) and fMRI to assess the behavioral and neural consequences of cerebellar tDCS during a sentence completion task. Task-based and resting-state fMRI data were acquired in healthy human adults ( n = 32; μ = 23.1 years) both before and after 20 min of 1.5 mA anodal ( n = 18) or sham ( n = 14) tDCS applied to the right posterolateral cerebellum. In the sentence completion task, the first four words of the sentence modulated the predictability of the final target word. In some sentences, the preceding context strongly predicted the target word, whereas other sentences were nonpredictive. Completion of predictive sentences increased activation in right Crus I/II of the cerebellum. Relative to sham tDCS, anodal tDCS increased activation in right Crus I/II during semantic prediction and enhanced resting-state functional connectivity between hubs of the reading/language networks. These results are consistent with a role for the right posterolateral cerebellum beyond motor aspects of language, and suggest that cerebellar internal models of linguistic stimuli support semantic prediction. SIGNIFICANCE STATEMENT Cerebellar involvement in language tasks and language networks is now well established, yet the specific cerebellar contribution to language processing remains unclear. It is thought that the cerebellum acquires internal models of mental processes that enable prediction, allowing for the optimization of behavior. Here we combined neuroimaging and neuromodulation to provide evidence that the cerebellum is specifically involved in semantic prediction during sentence processing. We found that activation within right Crus I/II was enhanced when semantic predictions were made, and we show that modulation of this region with transcranial direct current stimulation alters both activation patterns and functional connectivity within whole-brain language networks. For the first time, these data show that cerebellar neuromodulation impacts activation patterns specifically during predictive language processing. Copyright © 2017 the authors 0270-6474/17/371604-10$15.00/0.

Predicting Multicomponent Adsorption Isotherms in Open-Metal Site Materials Using Force Field Calculations Based on Energy Decomposed Density Functional Theory.

PubMed

Heinen, Jurn; Burtch, Nicholas C; Walton, Krista S; Fonseca Guerra, Célia; Dubbeldam, David

2016-12-12

For the design of adsorptive-separation units, knowledge is required of the multicomponent adsorption behavior. Ideal adsorbed solution theory (IAST) breaks down for olefin adsorption in open-metal site (OMS) materials due to non-ideal donor-acceptor interactions. Using a density-function-theory-based energy decomposition scheme, we develop a physically justifiable classical force field that incorporates the missing orbital interactions using an appropriate functional form. Our first-principles derived force field shows greatly improved quantitative agreement with the inflection points, initial uptake, saturation capacity, and enthalpies of adsorption obtained from our in-house adsorption experiments. While IAST fails to make accurate predictions, our improved force field model is able to correctly predict the multicomponent behavior. Our approach is also transferable to other OMS structures, allowing the accurate study of their separation performances for olefins/paraffins and further mixtures involving complex donor-acceptor interactions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

High-throughput, pooled sequencing identifies mutations in NUBPL and FOXRED1 in human complex I deficiency

PubMed Central

Calvo, Sarah E; Tucker, Elena J; Compton, Alison G; Kirby, Denise M; Crawford, Gabriel; Burtt, Noel P; Rivas, Manuel A; Guiducci, Candace; Bruno, Damien L; Goldberger, Olga A; Redman, Michelle C; Wiltshire, Esko; Wilson, Callum J; Altshuler, David; Gabriel, Stacey B; Daly, Mark J; Thorburn, David R; Mootha, Vamsi K

2010-01-01

Discovering the molecular basis of mitochondrial respiratory chain disease is challenging given the large number of both mitochondrial and nuclear genes involved. We report a strategy of focused candidate gene prediction, high-throughput sequencing, and experimental validation to uncover the molecular basis of mitochondrial complex I (CI) disorders. We created five pools of DNA from a cohort of 103 patients and then performed deep sequencing of 103 candidate genes to spotlight 151 rare variants predicted to impact protein function. We used confirmatory experiments to establish genetic diagnoses in 22% of previously unsolved cases, and discovered that defects in NUBPL and FOXRED1 can cause CI deficiency. Our study illustrates how large-scale sequencing, coupled with functional prediction and experimental validation, can reveal novel disease-causing mutations in individual patients. PMID:20818383

Using geophysical images of a watershed subsurface to predict soil textural properties

USDA-ARS?s Scientific Manuscript database

Subsurface architecture, in particular changes in soil type across the landscape, is an important control on the hydrological and ecological function of a watershed. Traditional methods of mapping soils involving subjective assignment of soil boundaries are inadequate for studies requiring a quantit...

Machine learning prediction for classification of outcomes in local minimisation

NASA Astrophysics Data System (ADS)

Das, Ritankar; Wales, David J.

2017-01-01

Machine learning schemes are employed to predict which local minimum will result from local energy minimisation of random starting configurations for a triatomic cluster. The input data consists of structural information at one or more of the configurations in optimisation sequences that converge to one of four distinct local minima. The ability to make reliable predictions, in terms of the energy or other properties of interest, could save significant computational resources in sampling procedures that involve systematic geometry optimisation. Results are compared for two energy minimisation schemes, and for neural network and quadratic functions of the inputs.

Individual differences in intrinsic brain connectivity predict decision strategy.

PubMed

Barnes, Kelly Anne; Anderson, Kevin M; Plitt, Mark; Martin, Alex

2014-10-15

When humans are provided with ample time to make a decision, individual differences in strategy emerge. Using an adaptation of a well-studied decision making paradigm, motion direction discrimination, we probed the neural basis of individual differences in strategy. We tested whether strategies emerged from moment-to-moment reconfiguration of functional brain networks involved in decision making with task-evoked functional MRI (fMRI) and whether intrinsic properties of functional brain networks, measured at rest with functional connectivity MRI (fcMRI), were associated with strategy use. We found that human participants reliably selected one of two strategies across 2 days of task performance, either continuously accumulating evidence or waiting for task difficulty to decrease. Individual differences in decision strategy were predicted both by the degree of task-evoked activation of decision-related brain regions and by the strength of pretask correlated spontaneous brain activity. These results suggest that spontaneous brain activity constrains strategy selection on perceptual decisions.

Drawing links between the autism cognitive profile and imagination: Executive function and processing bias in imaginative drawings by children with and without autism.

PubMed

Ten Eycke, Kayla D; Müller, Ulrich

2018-02-01

Little is known about the relation between cognitive processes and imagination and whether this relation differs between neurotypically developing children and children with autism. To address this issue, we administered a cognitive task battery and Karmiloff-Smith's drawing task, which requires children to draw imaginative people and houses. For children with autism, executive function significantly predicted imaginative drawing. In neurotypically developing controls, executive function and cognitive-perceptual processing style predicted imaginative drawing, but these associations were moderated by mental age. In younger (neurotypically developing) children, better executive function and a local processing bias were associated with imagination; in older children, only a global bias was associated with imagination. These findings suggest that (a) with development there are changes in the type of cognitive processes involved in imagination and (b) children with autism employ a unique cognitive strategy in imaginative drawing.

Longitudinal prediction and concurrent functioning of adolescent girls demonstrating various profiles of dating violence and victimization.

PubMed

Chiodo, Debbie; Crooks, Claire V; Wolfe, David A; McIsaac, Caroline; Hughes, Ray; Jaffe, Peter G

2012-08-01

Adolescent girls are involved in physical dating violence as both perpetrators and victims, and there are negative consequences associated with each of these behaviors. This article used a prospective design with 519 girls dating in grade 9 to predict profiles of dating violence in grade 11 based on relationships with families of origin (child maltreatment experiences, harsh parenting), and peers (harassment, delinquency, relational aggression). In addition, dating violence profiles were compared on numerous indices of adjustment (school connectedness, grades, self-efficacy and community connectedness) and maladjustment (suicide attempts, distress, delinquency, sexual behavior) for descriptive purposes. The most common profile was no dating violence (n = 367) followed by mutual violence (n = 81). Smaller numbers of girls reported victimization or perpetration only (ns = 39 and 32, respectively). Predicting grade 11 dating violence profile membership from grade 9 relationships was limited, although delinquency, parental rejection, and sexual harassment perpetration predicted membership to the mutually violent group, and delinquency predicted the perpetrator-only group. Compared to the non-violent group, the mutually violent girls in grade 11 had lower grades, poorer self-efficacy, and lower school connectedness and community involvement. Furthermore, they had higher rates of peer aggression and delinquency, were less likely to use condoms and were much more likely to have considered suicide. There were fewer differences among the profiles for girls involved with dating violence. In addition, the victims-only group reported higher rates of sexual intercourse, comparable to the mutually violent group and those involved in nonviolent relationships. Implications for prevention and intervention are highlighted.

Machine Learning Analysis Identifies Drosophila Grunge/Atrophin as an Important Learning and Memory Gene Required for Memory Retention and Social Learning.

PubMed

Kacsoh, Balint Z; Greene, Casey S; Bosco, Giovanni

2017-11-06

High-throughput experiments are becoming increasingly common, and scientists must balance hypothesis-driven experiments with genome-wide data acquisition. We sought to predict novel genes involved in Drosophila learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified Grunge/Atrophin ( Gug/Atro ), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that Gug has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of Gug specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that Gug function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for Gug as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction. Copyright © 2017 Kacsoh et al.

Application of backpropagation artificial neural network prediction model for the PAH bioremediation of polluted soil.

PubMed

Olawoyin, Richard

2016-10-01

The backpropagation (BP) artificial neural network (ANN) is a renowned and extensively functional mathematical tool used for time-series predictions and approximations; which also define results for non-linear functions. ANNs are vital tools in the predictions of toxicant levels, such as polycyclic aromatic hydrocarbons (PAH) potentially derived from anthropogenic activities in the microenvironment. In the present work, BP ANN was used as a prediction tool to study the potential toxicity of PAH carcinogens (PAHcarc) in soils. Soil samples (16 × 4 = 64) were collected from locations in South-southern Nigeria. The concentration of PAHcarc in laboratory cultivated white melilot, Melilotus alba roots grown on treated soils was predicted using ANN model training. Results indicated the Levenberg-Marquardt back-propagation training algorithm converged in 2.5E+04 epochs at an average RMSE value of 1.06E-06. The averagedR(2) comparison between the measured and predicted outputs was 0.9994. It may be deduced from this study that, analytical processes involving environmental risk assessment as used in this study can successfully provide prompt prediction and source identification of major soil toxicants. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hidden state prediction: a modification of classic ancestral state reconstruction algorithms helps unravel complex symbioses

PubMed Central

Zaneveld, Jesse R. R.; Thurber, Rebecca L. V.

2014-01-01

Complex symbioses between animal or plant hosts and their associated microbiotas can involve thousands of species and millions of genes. Because of the number of interacting partners, it is often impractical to study all organisms or genes in these host-microbe symbioses individually. Yet new phylogenetic predictive methods can use the wealth of accumulated data on diverse model organisms to make inferences into the properties of less well-studied species and gene families. Predictive functional profiling methods use evolutionary models based on the properties of studied relatives to put bounds on the likely characteristics of an organism or gene that has not yet been studied in detail. These techniques have been applied to predict diverse features of host-associated microbial communities ranging from the enzymatic function of uncharacterized genes to the gene content of uncultured microorganisms. We consider these phylogenetically informed predictive techniques from disparate fields as examples of a general class of algorithms for Hidden State Prediction (HSP), and argue that HSP methods have broad value in predicting organismal traits in a variety of contexts, including the study of complex host-microbe symbioses. PMID:25202302

Genome-wide protein-protein interactions and protein function exploration in cyanobacteria

PubMed Central

Lv, Qi; Ma, Weimin; Liu, Hui; Li, Jiang; Wang, Huan; Lu, Fang; Zhao, Chen; Shi, Tieliu

2015-01-01

Genome-wide network analysis is well implemented to study proteins of unknown function. Here, we effectively explored protein functions and the biological mechanism based on inferred high confident protein-protein interaction (PPI) network in cyanobacteria. We integrated data from seven different sources and predicted 1,997 PPIs, which were evaluated by experiments in molecular mechanism, text mining of literatures in proved direct/indirect evidences, and “interologs” in conservation. Combined the predicted PPIs with known PPIs, we obtained 4,715 no-redundant PPIs (involving 3,231 proteins covering over 90% of genome) to generate the PPI network. Based on the PPI network, terms in Gene ontology (GO) were assigned to function-unknown proteins. Functional modules were identified by dissecting the PPI network into sub-networks and analyzing pathway enrichment, with which we investigated novel function of underlying proteins in protein complexes and pathways. Examples of photosynthesis and DNA repair indicate that the network approach is a powerful tool in protein function analysis. Overall, this systems biology approach provides a new insight into posterior functional analysis of PPIs in cyanobacteria. PMID:26490033

Modeling Scramjet Flows with Variable Turbulent Prandtl and Schmidt Numbers

NASA Technical Reports Server (NTRS)

Xiao, X.; Hassan, H. A.; Baurle, R. A.

2006-01-01

A complete turbulence model, where the turbulent Prandtl and Schmidt numbers are calculated as part of the solution and where averages involving chemical source terms are modeled, is presented. The ability of avoiding the use of assumed or evolution Probability Distribution Functions (PDF's) results in a highly efficient algorithm for reacting flows. The predictions of the model are compared with two sets of experiments involving supersonic mixing and one involving supersonic combustion. The results demonstrate the need for consideration of turbulence/chemistry interactions in supersonic combustion. In general, good agreement with experiment is indicated.

Flight-Test Evaluation of Flutter-Prediction Methods

NASA Technical Reports Server (NTRS)

Lind, RIck; Brenner, Marty

2003-01-01

The flight-test community routinely spends considerable time and money to determine a range of flight conditions, called a flight envelope, within which an aircraft is safe to fly. The cost of determining a flight envelope could be greatly reduced if there were a method of safely and accurately predicting the speed associated with the onset of an instability called flutter. Several methods have been developed with the goal of predicting flutter speeds to improve the efficiency of flight testing. These methods include (1) data-based methods, in which one relies entirely on information obtained from the flight tests and (2) model-based approaches, in which one relies on a combination of flight data and theoretical models. The data-driven methods include one based on extrapolation of damping trends, one that involves an envelope function, one that involves the Zimmerman-Weissenburger flutter margin, and one that involves a discrete-time auto-regressive model. An example of a model-based approach is that of the flutterometer. These methods have all been shown to be theoretically valid and have been demonstrated on simple test cases; however, until now, they have not been thoroughly evaluated in flight tests. An experimental apparatus called the Aerostructures Test Wing (ATW) was developed to test these prediction methods.

Prediction of microRNAs Associated with Human Diseases Based on Weighted k Most Similar Neighbors

PubMed Central

Guo, Maozu; Guo, Yahong; Li, Jinbao; Ding, Jian; Liu, Yong; Dai, Qiguo; Li, Jin; Teng, Zhixia; Huang, Yufei

2013-01-01

Background The identification of human disease-related microRNAs (disease miRNAs) is important for further investigating their involvement in the pathogenesis of diseases. More experimentally validated miRNA-disease associations have been accumulated recently. On the basis of these associations, it is essential to predict disease miRNAs for various human diseases. It is useful in providing reliable disease miRNA candidates for subsequent experimental studies. Methodology/Principal Findings It is known that miRNAs with similar functions are often associated with similar diseases and vice versa. Therefore, the functional similarity of two miRNAs has been successfully estimated by measuring the semantic similarity of their associated diseases. To effectively predict disease miRNAs, we calculated the functional similarity by incorporating the information content of disease terms and phenotype similarity between diseases. Furthermore, the members of miRNA family or cluster are assigned higher weight since they are more probably associated with similar diseases. A new prediction method, HDMP, based on weighted k most similar neighbors is presented for predicting disease miRNAs. Experiments validated that HDMP achieved significantly higher prediction performance than existing methods. In addition, the case studies examining prostatic neoplasms, breast neoplasms, and lung neoplasms, showed that HDMP can uncover potential disease miRNA candidates. Conclusions The superior performance of HDMP can be attributed to the accurate measurement of miRNA functional similarity, the weight assignment based on miRNA family or cluster, and the effective prediction based on weighted k most similar neighbors. The online prediction and analysis tool is freely available at http://nclab.hit.edu.cn/hdmpred. PMID:23950912

Prospective Relations between Organized Activity Participation and Psychopathology during Adolescence

ERIC Educational Resources Information Center

Bohnert, Amy M.; Garber, Judy

2007-01-01

This longitudinal study examined psychopathology as a predictor and outcome of organized activity involvement during high school among 198 adolescents who varied in risk for psychopathology as a function of their mother's depression history. Higher levels of internalizing and externalizing symptoms in eighth grade significantly predicted lower…

First Steps in Computational Systems Biology: A Practical Session in Metabolic Modeling and Simulation

ERIC Educational Resources Information Center

Reyes-Palomares, Armando; Sanchez-Jimenez, Francisca; Medina, Miguel Angel

2009-01-01

A comprehensive understanding of biological functions requires new systemic perspectives, such as those provided by systems biology. Systems biology approaches are hypothesis-driven and involve iterative rounds of model building, prediction, experimentation, model refinement, and development. Developments in computer science are allowing for ever…

Biological Motion Task Performance Predicts Superior Temporal Sulcus Activity

ERIC Educational Resources Information Center

Herrington, John D.; Nymberg, Charlotte; Schultz, Robert T.

2011-01-01

Numerous studies implicate superior temporal sulcus (STS) in the perception of human movement. More recent theories hold that STS is also involved in the "understanding" of human movement. However, almost no studies to date have associated STS function with observable variability in action understanding. The present study directly associated STS…

Genome Wide Re-Annotation of Caldicellulosiruptor saccharolyticus with New Insights into Genes Involved in Biomass Degradation and Hydrogen Production

PubMed Central

Chowdhary, Nupoor; Selvaraj, Ashok; KrishnaKumaar, Lakshmi; Kumar, Gopal Ramesh

2015-01-01

Caldicellulosiruptor saccharolyticus has proven itself to be an excellent candidate for biological hydrogen (H2) production, but still it has major drawbacks like sensitivity to high osmotic pressure and low volumetric H2 productivity, which should be considered before it can be used industrially. A whole genome re-annotation work has been carried out as an attempt to update the incomplete genome information that causes gap in the knowledge especially in the area of metabolic engineering, to improve the H2 producing capabilities of C. saccharolyticus. Whole genome re-annotation was performed through manual means for 2,682 Coding Sequences (CDSs). Bioinformatics tools based on sequence similarity, motif search, phylogenetic analysis and fold recognition were employed for re-annotation. Our methodology could successfully add functions for 409 hypothetical proteins (HPs), 46 proteins previously annotated as putative and assigned more accurate functions for the known protein sequences. Homology based gene annotation has been used as a standard method for assigning function to novel proteins, but over the past few years many non-homology based methods such as genomic context approaches for protein function prediction have been developed. Using non-homology based functional prediction methods, we were able to assign cellular processes or physical complexes for 249 hypothetical sequences. Our re-annotation pipeline highlights the addition of 231 new CDSs generated from MicroScope Platform, to the original genome with functional prediction for 49 of them. The re-annotation of HPs and new CDSs is stored in the relational database that is available on the MicroScope web-based platform. In parallel, a comparative genome analyses were performed among the members of genus Caldicellulosiruptor to understand the function and evolutionary processes. Further, with results from integrated re-annotation studies (homology and genomic context approach), we strongly suggest that Csac_0437 and Csac_0424 encode for glycoside hydrolases (GH) and are proposed to be involved in the decomposition of recalcitrant plant polysaccharides. Similarly, HPs: Csac_0732, Csac_1862, Csac_1294 and Csac_0668 are suggested to play a significant role in biohydrogen production. Function prediction of these HPs by using our integrated approach will considerably enhance the interpretation of large-scale experiments targeting this industrially important organism. PMID:26196387

Genome Wide Re-Annotation of Caldicellulosiruptor saccharolyticus with New Insights into Genes Involved in Biomass Degradation and Hydrogen Production.

PubMed

Chowdhary, Nupoor; Selvaraj, Ashok; KrishnaKumaar, Lakshmi; Kumar, Gopal Ramesh

2015-01-01

Caldicellulosiruptor saccharolyticus has proven itself to be an excellent candidate for biological hydrogen (H2) production, but still it has major drawbacks like sensitivity to high osmotic pressure and low volumetric H2 productivity, which should be considered before it can be used industrially. A whole genome re-annotation work has been carried out as an attempt to update the incomplete genome information that causes gap in the knowledge especially in the area of metabolic engineering, to improve the H2 producing capabilities of C. saccharolyticus. Whole genome re-annotation was performed through manual means for 2,682 Coding Sequences (CDSs). Bioinformatics tools based on sequence similarity, motif search, phylogenetic analysis and fold recognition were employed for re-annotation. Our methodology could successfully add functions for 409 hypothetical proteins (HPs), 46 proteins previously annotated as putative and assigned more accurate functions for the known protein sequences. Homology based gene annotation has been used as a standard method for assigning function to novel proteins, but over the past few years many non-homology based methods such as genomic context approaches for protein function prediction have been developed. Using non-homology based functional prediction methods, we were able to assign cellular processes or physical complexes for 249 hypothetical sequences. Our re-annotation pipeline highlights the addition of 231 new CDSs generated from MicroScope Platform, to the original genome with functional prediction for 49 of them. The re-annotation of HPs and new CDSs is stored in the relational database that is available on the MicroScope web-based platform. In parallel, a comparative genome analyses were performed among the members of genus Caldicellulosiruptor to understand the function and evolutionary processes. Further, with results from integrated re-annotation studies (homology and genomic context approach), we strongly suggest that Csac_0437 and Csac_0424 encode for glycoside hydrolases (GH) and are proposed to be involved in the decomposition of recalcitrant plant polysaccharides. Similarly, HPs: Csac_0732, Csac_1862, Csac_1294 and Csac_0668 are suggested to play a significant role in biohydrogen production. Function prediction of these HPs by using our integrated approach will considerably enhance the interpretation of large-scale experiments targeting this industrially important organism.

Integrative analyses of miRNA and proteomics identify potential biological pathways associated with onset of pulmonary fibrosis in the bleomycin rat model

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

Fukunaga, Satoki; Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd., 3-1-98 Kasugade-Naka, Konohana-ku, Osaka 554-8558; Kakehashi, Anna

To determine miRNAs and their predicted target proteins regulatory networks which are potentially involved in onset of pulmonary fibrosis in the bleomycin rat model, we conducted integrative miRNA microarray and iTRAQ-coupled LC-MS/MS proteomic analyses, and evaluated the significance of altered biological functions and pathways. We observed that alterations of miRNAs and proteins are associated with the early phase of bleomycin-induced pulmonary fibrosis, and identified potential target pairs by using ingenuity pathway analysis. Using the data set of these alterations, it was demonstrated that those miRNAs, in association with their predicted target proteins, are potentially involved in canonical pathways reflective ofmore » initial epithelial injury and fibrogenic processes, and biofunctions related to induction of cellular development, movement, growth, and proliferation. Prediction of activated functions suggested that lung cells acquire proliferative, migratory, and invasive capabilities, and resistance to cell death especially in the very early phase of bleomycin-induced pulmonary fibrosis. The present study will provide new insights for understanding the molecular pathogenesis of idiopathic pulmonary fibrosis. - Highlights: • We analyzed bleomycin-induced pulmonary fibrosis in the rat. • Integrative analyses of miRNA microarray and proteomics were conducted. • We determined the alterations of miRNAs and their potential target proteins. • The alterations may control biological functions and pathways in pulmonary fibrosis. • Our result may provide new insights of pulmonary fibrosis.« less

Self-determination theory and diminished functioning: the role of interpersonal control and psychological need thwarting.

PubMed

Bartholomew, Kimberley J; Ntoumanis, Nikos; Ryan, Richard M; Bosch, Jos A; Thøgersen-Ntoumani, Cecilie

2011-11-01

Drawing from self-determination theory, three studies explored the social-environmental conditions that satisfy versus thwart psychological needs and, in turn, affect psychological functioning and well-being or ill-being. In cross-sectional Studies 1 and 2, structural equation modeling analyses supported latent factor models in which need satisfaction was predicted by athletes' perceptions of autonomy support, and need thwarting was better predicted by coach control. Athletes' perceptions of need satisfaction predicted positive outcomes associated with sport participation (vitality and positive affect), whereas need thwarting more consistently predicted maladaptive outcomes (disordered eating, burnout, depression, negative affect, and physical symptoms). In addition, athletes' perceptions of psychological need thwarting were significantly associated with perturbed physiological arousal (elevated levels of secretory immunoglobulin A) prior to training. The final study involved the completion of a diary and supported the relations observed in the cross-sectional studies at a daily level. These findings have important implications for the operationalization and measurement of interpersonal styles and psychological needs.

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

Simonetto, Andrea; Dall'Anese, Emiliano

This article develops online algorithms to track solutions of time-varying constrained optimization problems. Particularly, resembling workhorse Kalman filtering-based approaches for dynamical systems, the proposed methods involve prediction-correction steps to provably track the trajectory of the optimal solutions of time-varying convex problems. The merits of existing prediction-correction methods have been shown for unconstrained problems and for setups where computing the inverse of the Hessian of the cost function is computationally affordable. This paper addresses the limitations of existing methods by tackling constrained problems and by designing first-order prediction steps that rely on the Hessian of the cost function (and do notmore » require the computation of its inverse). In addition, the proposed methods are shown to improve the convergence speed of existing prediction-correction methods when applied to unconstrained problems. Numerical simulations corroborate the analytical results and showcase performance and benefits of the proposed algorithms. A realistic application of the proposed method to real-time control of energy resources is presented.« less

From Structure to Function: A Comprehensive Compendium of Tools to Unveil Protein Domains and Understand Their Role in Cytokinesis.

PubMed

Rincon, Sergio A; Paoletti, Anne

2016-01-01

Unveiling the function of a novel protein is a challenging task that requires careful experimental design. Yeast cytokinesis is a conserved process that involves modular structural and regulatory proteins. For such proteins, an important step is to identify their domains and structural organization. Here we briefly discuss a collection of methods commonly used for sequence alignment and prediction of protein structure that represent powerful tools for the identification homologous domains and design of structure-function approaches to test experimentally the function of multi-domain proteins such as those implicated in yeast cytokinesis.

Accurate prediction of interfacial residues in two-domain proteins using evolutionary information: implications for three-dimensional modeling.

PubMed

Bhaskara, Ramachandra M; Padhi, Amrita; Srinivasan, Narayanaswamy

2014-07-01

With the preponderance of multidomain proteins in eukaryotic genomes, it is essential to recognize the constituent domains and their functions. Often function involves communications across the domain interfaces, and the knowledge of the interacting sites is essential to our understanding of the structure-function relationship. Using evolutionary information extracted from homologous domains in at least two diverse domain architectures (single and multidomain), we predict the interface residues corresponding to domains from the two-domain proteins. We also use information from the three-dimensional structures of individual domains of two-domain proteins to train naïve Bayes classifier model to predict the interfacial residues. Our predictions are highly accurate (∼85%) and specific (∼95%) to the domain-domain interfaces. This method is specific to multidomain proteins which contain domains in at least more than one protein architectural context. Using predicted residues to constrain domain-domain interaction, rigid-body docking was able to provide us with accurate full-length protein structures with correct orientation of domains. We believe that these results can be of considerable interest toward rational protein and interaction design, apart from providing us with valuable information on the nature of interactions. © 2013 Wiley Periodicals, Inc.

A bioinformatics prediction approach towards analyzing the glycosylation, co-expression and interaction patterns of epithelial membrane antigen (EMA/MUC1)

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

Kalra, Rajkumar S., E-mail: renu-wadhwa@aist.go.jp; Wadhwa, Renu, E-mail: renu-wadhwa@aist.go.jp

2015-02-27

Epithelial membrane antigen (EMA or MUC1) is a heavily glycosylated, type I transmembrane glycoprotein commonly expressed by epithelial cells of duct organs. It has been shown to be aberrantly glycosylated in several diseases including cancer. Protein sequence based annotation and analysis of glycosylation profile of glycoproteins by robust computational and comprehensive algorithms provides possible insights to the mechanism(s) of anomalous glycosylation. In present report, by using a number of bioinformatics applications we studied EMA/MUC1 and explored its trans-membrane structural domain sequence that is widely subjected to glycosylation. Exploration of different extracellular motifs led to prediction of N and O-linked glycosylationmore » target sites. Based on the putative O-linked target sites, glycosylated moieties and pathways were envisaged. Furthermore, Protein network analysis demonstrated physical interaction of EMA with a number of proteins and confirmed its functional involvement in cell growth and proliferation pathways. Gene Ontology analysis suggested an involvement of EMA in a number of functions including signal transduction, protein binding, processing and transport along with glycosylation. Thus, present study explored potential of bioinformatics prediction approach in analyzing glycosylation, co-expression and interaction patterns of EMA/MUC1 glycoprotein.« less

Implications of gambling problems for family and interpersonal adjustment: results from the Quinte Longitudinal Study.

PubMed

Cowlishaw, Sean; Suomi, Aino; Rodgers, Bryan

2016-09-01

To evaluate (1) whether gambling problems predict overall trajectories of change in family or interpersonal adjustment and (2) whether annual measures of gambling problems predict time-specific decreases in family or interpersonal adjustment, concurrently and prospectively. The Quinte Longitudinal Study (QLS) involved random-digit dialling of telephone numbers around the city of Belleville, Canada to recruit 'general population' and 'at-risk' groups (the latter oversampling people likely to develop problems). Five waves of assessment were conducted (2006-10). Latent Trajectory Modelling (LTM) estimated overall trajectories of family and interpersonal adjustment, which were predicted by gambling problems, and also estimated how time-specific problems predicted deviations from these trajectories. Southeast Ontario, Canada. Community sample of Canadian adults (n = 4121). The Problem Gambling Severity Index (PGSI) defined at-risk gambling (ARG: PGSI 1-2) and moderate-risk/problem gambling (MR/PG: PGSI 3+). Outcomes included: (1) family functioning, assessed using a seven-point rating of overall functioning; (2) social support, assessed using items from the Non-support subscale of the Personality Assessment Inventory; and (3) relationship satisfaction, measured by the Kansas Marital Satisfaction Scale. Baseline measures of ARG and MR/PG did not predict rates of change in trajectories of family or interpersonal adjustment. Rather, the annual measures of MR/PG predicted time-specific decreases in family functioning (estimate: -0.11, P < 0.01), social support (estimate: -0.28, P < 0.01) and relationship satisfaction (estimate: -0.53, P < 0.01). ARG predicted concurrent levels of family functioning (estimate: -0.07, P < 0.01). There were time-lagged effects of MR/PG on subsequent levels of family functioning (estimate: -0.12, P < 0.01) and social support (estimate: -0.24, P < 0.01). In a longitudinal study of Canadian adults, moderate-risk/problem gambling did not predict overall trajectories of family or interpersonal adjustment. Rather, the annual measures of moderate-risk/problem gambling predicted time-specific and concurrent decreases in all outcomes, and lower family functioning and social support across adjacent waves. © 2016 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Phylogenomic detection and functional prediction of genes potentially important for plant meiosis.

PubMed

Zhang, Luoyan; Kong, Hongzhi; Ma, Hong; Yang, Ji

2018-02-15

Meiosis is a specialized type of cell division necessary for sexual reproduction in eukaryotes. A better understanding of the cytological procedures of meiosis has been achieved by comprehensive cytogenetic studies in plants, while the genetic mechanisms regulating meiotic progression remain incompletely understood. The increasing accumulation of complete genome sequences and large-scale gene expression datasets has provided a powerful resource for phylogenomic inference and unsupervised identification of genes involved in plant meiosis. By integrating sequence homology and expression data, 164, 131, 124 and 162 genes potentially important for meiosis were identified in the genomes of Arabidopsis thaliana, Oryza sativa, Selaginella moellendorffii and Pogonatum aloides, respectively. The predicted genes were assigned to 45 meiotic GO terms, and their functions were related to different processes occurring during meiosis in various organisms. Most of the predicted meiotic genes underwent lineage-specific duplication events during plant evolution, with about 30% of the predicted genes retaining only a single copy in higher plant genomes. The results of this study provided clues to design experiments for better functional characterization of meiotic genes in plants, promoting the phylogenomic approach to the evolutionary dynamics of the plant meiotic machineries. Copyright © 2017 Elsevier B.V. All rights reserved.

Predicting effects of climate change on the composition and function of soil microbial communities

NASA Astrophysics Data System (ADS)

Dubinsky, E.; Brodie, E.; Myint, C.; Ackerly, D.; van Nostrand, J.; Bird, J.; Zhou, J.; Andersen, G.; Firestone, M.

2008-12-01

Complex soil microbial communities regulate critical ecosystem processes that will be altered by climate change. A critical step towards predicting the impacts of climate change on terrestrial ecosystems is to determine the primary controllers of soil microbial community composition and function, and subsequently evaluate climate change scenarios that alter these controllers. We surveyed complex soil bacterial and archaeal communities across a range of climatic and edaphic conditions to identify critical controllers of soil microbial community composition in the field and then tested the resulting predictions using a 2-year manipulation of precipitation and temperature using mesocosms of California annual grasslands. Community DNA extracted from field soils sampled from six different ecosystems was assayed for bacterial and archaeal communities using high-density phylogenetic microarrays as well as functional gene arrays. Correlations among the relative abundances of thousands of microbial taxa and edaphic factors such as soil moisture and nutrient content provided a basis for predicting community responses to changing soil conditions. Communities of soil bacteria and archaea were strongly structured by single environmental predictors, particularly variables related to soil water. Bacteria in the Actinomycetales and Bacilli consistently demonstrated a strong negative response to increasing soil moisture, while taxa in a greater variety of lineages responded positively to increasing soil moisture. In the climate change experiment, overall bacterial community structure was impacted significantly by total precipitation but not by plant species. Changes in soil moisture due to decreased rainfall resulted in significant and predictable alterations in community structure. Over 70% of the bacterial taxa in common with the cross-ecosystem study responded as predicted to altered precipitation, with the most conserved response from Actinobacteria. The functional consequences of these predictable changes in community composition were measured with functional arrays that detect genes involved in the metabolism of carbon, nitrogen and other elements. The response of soil microbial communities to altered precipitation can be predicted from the distribution of microbial taxa across moisture gradients.

Metataxonomic profiling and prediction of functional behaviour of wheat straw degrading microbial consortia

PubMed Central

2014-01-01

Background Mixed microbial cultures, in which bacteria and fungi interact, have been proposed as an efficient way to deconstruct plant waste. The characterization of specific microbial consortia could be the starting point for novel biotechnological applications related to the efficient conversion of lignocellulose to cello-oligosaccharides, plastics and/or biofuels. Here, the diversity, composition and predicted functional profiles of novel bacterial-fungal consortia are reported, on the basis of replicated aerobic wheat straw enrichment cultures. Results In order to set up biodegradative microcosms, microbial communities were retrieved from a forest soil and introduced into a mineral salt medium containing 1% of (un)treated wheat straw. Following each incubation step, sequential transfers were carried out using 1 to 1,000 dilutions. The microbial source next to three sequential batch cultures (transfers 1, 3 and 10) were analyzed by bacterial 16S rRNA gene and fungal ITS1 pyrosequencing. Faith’s phylogenetic diversity values became progressively smaller from the inoculum to the sequential batch cultures. Moreover, increases in the relative abundances of Enterobacteriales, Pseudomonadales, Flavobacteriales and Sphingobacteriales were noted along the enrichment process. Operational taxonomic units affiliated with Acinetobacter johnsonii, Pseudomonas putida and Sphingobacterium faecium were abundant and the underlying strains were successfully isolated. Interestingly, Klebsiella variicola (OTU1062) was found to dominate in both consortia, whereas K. variicola-affiliated strains retrieved from untreated wheat straw consortia showed endoglucanase/xylanase activities. Among the fungal players with high biotechnological relevance, we recovered members of the genera Penicillium, Acremonium, Coniochaeta and Trichosporon. Remarkably, the presence of peroxidases, alpha-L-fucosidases, beta-xylosidases, beta-mannases and beta-glucosidases, involved in lignocellulose degradation, was indicated by predictive bacterial metagenome reconstruction. Reassuringly, tests for specific (hemi)cellulolytic enzymatic activities, performed on the consortial secretomes, confirmed the presence of such gene functions. Conclusion In an in-depth characterization of two wheat straw degrading microbial consortia, we revealed the enrichment and selection of specific bacterial and fungal taxa that were presumably involved in (hemi) cellulose degradation. Interestingly, the microbial community composition was strongly influenced by the wheat straw pretreatment. Finally, the functional bacterial-metagenome prediction and the evaluation of enzymatic activities (at the consortial secretomes) revealed the presence and enrichment of proteins involved in the deconstruction of plant biomass. PMID:24955113

Stringent DDI-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Rezaei, Javad; Hugo, Willy; Gao, Shangzhi; Jin, Jingjing; Fan, Mengyuan; Yong, Chern-Han; Wozniak, Michal; Wong, Limsoon

2013-01-01

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are very important information to illuminate the infection mechanism of M. tuberculosis H37Rv. But current H. sapiens-M. tuberculosis H37Rv PPI data are very scarce. This seriously limits the study of the interaction between this important pathogen and its host H. sapiens. Computational prediction of H. sapiens-M. tuberculosis H37Rv PPIs is an important strategy to fill in the gap. Domain-domain interaction (DDI) based prediction is one of the frequently used computational approaches in predicting both intra-species and inter-species PPIs. However, the performance of DDI-based host-pathogen PPI prediction has been rather limited. We develop a stringent DDI-based prediction approach with emphasis on (i) differences between the specific domain sequences on annotated regions of proteins under the same domain ID and (ii) calculation of the interaction strength of predicted PPIs based on the interacting residues in their interaction interfaces. We compare our stringent DDI-based approach to a conventional DDI-based approach for predicting PPIs based on gold standard intra-species PPIs and coherent informative Gene Ontology terms assessment. The assessment results show that our stringent DDI-based approach achieves much better performance in predicting PPIs than the conventional approach. Using our stringent DDI-based approach, we have predicted a small set of reliable H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. We also analyze the H. sapiens-M. tuberculosis H37Rv PPIs predicted by our stringent DDI-based approach using cellular compartment distribution analysis, functional category enrichment analysis and pathway enrichment analysis. The analyses support the validity of our prediction result. Also, based on an analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent DDI-based approach, we have discovered some important properties of domains involved in host-pathogen PPIs. We find that both host and pathogen proteins involved in host-pathogen PPIs tend to have more domains than proteins involved in intra-species PPIs, and these domains have more interaction partners than domains on proteins involved in intra-species PPI. The stringent DDI-based prediction approach reported in this work provides a stringent strategy for predicting host-pathogen PPIs. It also performs better than a conventional DDI-based approach in predicting PPIs. We have predicted a small set of accurate H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies.

Improving antenatal risk assessment in women exposed to high risks.

PubMed

Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

2015-01-01

Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. © The Author(s) 2013.

Deletion of the transcriptional coactivator PGC1α in skeletal muscles is associated with reduced expression of genes related to oxidative muscle function

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

Hatazawa, Yukino; Research Fellow of Japan Society for the Promotion of Science, Tokyo; Minami, Kimiko

The expression of the transcriptional coactivator PGC1α is increased in skeletal muscles during exercise. Previously, we showed that increased PGC1α leads to prolonged exercise performance (the duration for which running can be continued) and, at the same time, increases the expression of branched-chain amino acid (BCAA) metabolism-related enzymes and genes that are involved in supplying substrates for the TCA cycle. We recently created mice with PGC1α knockout specifically in the skeletal muscles (PGC1α KO mice), which show decreased mitochondrial content. In this study, global gene expression (microarray) analysis was performed in the skeletal muscles of PGC1α KO mice compared withmore » that of wild-type control mice. As a result, decreased expression of genes involved in the TCA cycle, oxidative phosphorylation, and BCAA metabolism were observed. Compared with previously obtained microarray data on PGC1α-overexpressing transgenic mice, each gene showed the completely opposite direction of expression change. Bioinformatic analysis of the promoter region of genes with decreased expression in PGC1α KO mice predicted the involvement of several transcription factors, including a nuclear receptor, ERR, in their regulation. As PGC1α KO microarray data in this study show opposing findings to the PGC1α transgenic data, a loss-of-function experiment, as well as a gain-of-function experiment, revealed PGC1α’s function in the oxidative energy metabolism of skeletal muscles. - Highlights: • Microarray analysis was performed in the skeletal muscle of PGC1α KO mice. • Expression of genes in the oxidative energy metabolism was decreased. • Bioinformatic analysis of promoter region of the genes predicted involvement of ERR. • PGC1α KO microarray data in this study show the mirror image of transgenic data.« less

Hierarchical learning induces two simultaneous, but separable, prediction errors in human basal ganglia.

PubMed

Diuk, Carlos; Tsai, Karin; Wallis, Jonathan; Botvinick, Matthew; Niv, Yael

2013-03-27

Studies suggest that dopaminergic neurons report a unitary, global reward prediction error signal. However, learning in complex real-life tasks, in particular tasks that show hierarchical structure, requires multiple prediction errors that may coincide in time. We used functional neuroimaging to measure prediction error signals in humans performing such a hierarchical task involving simultaneous, uncorrelated prediction errors. Analysis of signals in a priori anatomical regions of interest in the ventral striatum and the ventral tegmental area indeed evidenced two simultaneous, but separable, prediction error signals corresponding to the two levels of hierarchy in the task. This result suggests that suitably designed tasks may reveal a more intricate pattern of firing in dopaminergic neurons. Moreover, the need for downstream separation of these signals implies possible limitations on the number of different task levels that we can learn about simultaneously.

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

Daily, Michael D.; Olsen, Brett N.; Schlesinger, Paul H.

In mammalian cells cholesterol is essential for membrane function, but in excess can be cytototoxic. The cellular response to acute cholesterol loading involves biophysical-based mechanisms that regulate cholesterol levels, through modulation of the “activity” or accessibility of cholesterol to extra-membrane acceptors. Experiments and united atom (UA) simulations show that at high concentrations of cholesterol, lipid bilayers thin significantly and cholesterol availability to external acceptors increases substantially. Such cholesterol activation is critical to its trafficking within cells. Here we aim to reduce the computational cost to enable simulation of large and complex systems involved in cholesterol regulation, such as those includingmore » oxysterols and cholesterol-sensing proteins. To accomplish this, we have modified the published MARTINI coarse-grained force field to improve its predictions of cholesterol-induced changes in both macroscopic and microscopic properties of membranes. Most notably, MARTINI fails to capture both the (macroscopic) area condensation and membrane thickening seen at less than 30% cholesterol and the thinning seen above 40% cholesterol. The thinning at high concentration is critical to cholesterol activation. Microscopic properties of interest include cholesterol-cholesterol radial distribution functions (RDFs), tilt angle, and accessible surface area. First, we develop an “angle-corrected” model wherein we modify the coarse-grained bond angle potentials based on atomistic simulations. This modification significantly improves prediction of macroscopic properties, most notably the thickening/thinning behavior, and also slightly improves microscopic property prediction relative to MARTINI. Second, we add to the angle correction a “volume correction” by also adjusting phospholipid bond lengths to achieve a more accurate volume per molecule. The angle + volume correction substantially further improves the quantitative agreement of the macroscopic properties (area per molecule and thickness) with united atom simulations. However, this improvement also reduces the accuracy of microscopic predictions like radial distribution functions and cholesterol tilt below that of either MARTINI or the angle-corrected model. Thus, while both of our forcefield corrections improve MARTINI, the combined angle and volume correction should be used for problems involving sterol effects on the overall structure of the membrane, while our angle-corrected model should be used in cases where the properties of individual lipid and sterol models are critically important.« less

Protein loop modeling using a new hybrid energy function and its application to modeling in inaccurate structural environments.

PubMed

Park, Hahnbeom; Lee, Gyu Rie; Heo, Lim; Seok, Chaok

2014-01-01

Protein loop modeling is a tool for predicting protein local structures of particular interest, providing opportunities for applications involving protein structure prediction and de novo protein design. Until recently, the majority of loop modeling methods have been developed and tested by reconstructing loops in frameworks of experimentally resolved structures. In many practical applications, however, the protein loops to be modeled are located in inaccurate structural environments. These include loops in model structures, low-resolution experimental structures, or experimental structures of different functional forms. Accordingly, discrepancies in the accuracy of the structural environment assumed in development of the method and that in practical applications present additional challenges to modern loop modeling methods. This study demonstrates a new strategy for employing a hybrid energy function combining physics-based and knowledge-based components to help tackle this challenge. The hybrid energy function is designed to combine the strengths of each energy component, simultaneously maintaining accurate loop structure prediction in a high-resolution framework structure and tolerating minor environmental errors in low-resolution structures. A loop modeling method based on global optimization of this new energy function is tested on loop targets situated in different levels of environmental errors, ranging from experimental structures to structures perturbed in backbone as well as side chains and template-based model structures. The new method performs comparably to force field-based approaches in loop reconstruction in crystal structures and better in loop prediction in inaccurate framework structures. This result suggests that higher-accuracy predictions would be possible for a broader range of applications. The web server for this method is available at http://galaxy.seoklab.org/loop with the PS2 option for the scoring function.

Medial orbitofrontal cortex codes relative rather than absolute value of financial rewards in humans.

PubMed

Elliott, R; Agnew, Z; Deakin, J F W

2008-05-01

Functional imaging studies in recent years have confirmed the involvement of orbitofrontal cortex (OFC) in human reward processing and have suggested that OFC responses are context-dependent. A seminal electrophysiological experiment in primates taught animals to associate abstract visual stimuli with differently valuable food rewards. Subsequently, pairs of these learned abstract stimuli were presented and firing of OFC neurons to the medium-value stimulus was measured. OFC firing was shown to depend on the relative value context. In this study, we developed a human analogue of this paradigm and scanned subjects using functional magnetic resonance imaging. The analysis compared neuronal responses to two superficially identical events, which differed only in terms of the preceding context. Medial OFC response to the same perceptual stimulus was greater when the stimulus predicted the more valuable of two rewards than when it predicted the less valuable. Additional responses were observed in other components of reward circuitry, the amygdala and ventral striatum. The central finding is consistent with the primate results and suggests that OFC neurons code relative rather than absolute reward value. Amygdala and striatal involvement in coding reward value is also consistent with recent functional imaging data. By using a simpler and less confounded paradigm than many functional imaging studies, we are able to demonstrate that relative financial reward value per se is coded in distinct subregions of an extended reward and decision-making network.

Transcriptomic analysis of Arabidopsis developing stems: a close-up on cell wall genes

PubMed Central

Minic, Zoran; Jamet, Elisabeth; San-Clemente, Hélène; Pelletier, Sandra; Renou, Jean-Pierre; Rihouey, Christophe; Okinyo, Denis PO; Proux, Caroline; Lerouge, Patrice; Jouanin, Lise

2009-01-01

Background Different strategies (genetics, biochemistry, and proteomics) can be used to study proteins involved in cell biogenesis. The availability of the complete sequences of several plant genomes allowed the development of transcriptomic studies. Although the expression patterns of some Arabidopsis thaliana genes involved in cell wall biogenesis were identified at different physiological stages, detailed microarray analysis of plant cell wall genes has not been performed on any plant tissues. Using transcriptomic and bioinformatic tools, we studied the regulation of cell wall genes in Arabidopsis stems, i.e. genes encoding proteins involved in cell wall biogenesis and genes encoding secreted proteins. Results Transcriptomic analyses of stems were performed at three different developmental stages, i.e., young stems, intermediate stage, and mature stems. Many genes involved in the synthesis of cell wall components such as polysaccharides and monolignols were identified. A total of 345 genes encoding predicted secreted proteins with moderate or high level of transcripts were analyzed in details. The encoded proteins were distributed into 8 classes, based on the presence of predicted functional domains. Proteins acting on carbohydrates and proteins of unknown function constituted the two most abundant classes. Other proteins were proteases, oxido-reductases, proteins with interacting domains, proteins involved in signalling, and structural proteins. Particularly high levels of expression were established for genes encoding pectin methylesterases, germin-like proteins, arabinogalactan proteins, fasciclin-like arabinogalactan proteins, and structural proteins. Finally, the results of this transcriptomic analyses were compared with those obtained through a cell wall proteomic analysis from the same material. Only a small proportion of genes identified by previous proteomic analyses were identified by transcriptomics. Conversely, only a few proteins encoded by genes having moderate or high level of transcripts were identified by proteomics. Conclusion Analysis of the genes predicted to encode cell wall proteins revealed that about 345 genes had moderate or high levels of transcripts. Among them, we identified many new genes possibly involved in cell wall biogenesis. The discrepancies observed between results of this transcriptomic study and a previous proteomic study on the same material revealed post-transcriptional mechanisms of regulation of expression of genes encoding cell wall proteins. PMID:19149885

Visual prediction and perceptual expertise

PubMed Central

Cheung, Olivia S.; Bar, Moshe

2012-01-01

Making accurate predictions about what may happen in the environment requires analogies between perceptual input and associations in memory. These elements of predictions are based on cortical representations, but little is known about how these processes can be enhanced by experience and training. On the other hand, studies on perceptual expertise have revealed that the acquisition of expertise leads to strengthened associative processing among features or objects, suggesting that predictions and expertise may be tightly connected. Here we review the behavioral and neural findings regarding the mechanisms involving prediction and expert processing, and highlight important possible overlaps between them. Future investigation should examine the relations among perception, memory and prediction skills as a function of expertise. The knowledge gained by this line of research will have implications for visual cognition research, and will advance our understanding of how the human brain can improve its ability to predict by learning from experience. PMID:22123523

Parental Involvement Protects against Self-Medication Behaviors during the High School Transition

PubMed Central

Gottfredson, Nisha C.; Hussong, Andrea M.

2011-01-01

We examined how drinking patterns change as adolescents transition to high school, particularly as a function of parental involvement. Stress associated with the transition to high school may deplete psychological resources for coping with negative daily emotions in an environment when opportunities to drink are more common. A cohort of elevated-risk middle school students completed daily negative affect (sadness, worry, anger, and stress) and alcohol use assessments before and after the transition to high school, resulting in a measurement burst design. Adolescents who reported less parental involvement were at higher risk for drinking on any given day. After (but not before) the transition to high school, daily within-person fluctuations of sadness predicted an increased probability of same-day alcohol use for adolescents who reported that their parents were minimally involved in their lives. The other negative affect indicators were not predictive of use. Our results suggest that the transition to high school may represent an important intervention leverage point, particularly for adolescents who lack adequate parental support to help them cope with day-to-day changes in sadness. PMID:21880433

Urine peptidome analysis predicts risk of end-stage renal disease and reveals proteolytic pathways involved in autosomal dominant polycystic kidney disease progression.

PubMed

Pejchinovski, Martin; Siwy, Justyna; Metzger, Jochen; Dakna, Mohammed; Mischak, Harald; Klein, Julie; Jankowski, Vera; Bae, Kyongtae T; Chapman, Arlene B; Kistler, Andreas D

2017-03-01

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by slowly progressive bilateral renal cyst growth ultimately resulting in loss of kidney function and end-stage renal disease (ESRD). Disease progression rate and age at ESRD are highly variable. Therapeutic interventions therefore require early risk stratification of patients and monitoring of disease progression in response to treatment. We used a urine peptidomic approach based on capillary electrophoresis-mass-spectrometry (CE-MS) to identify potential biomarkers reflecting the risk for early progression to ESRD in the Consortium of Radiologic Imaging in Polycystic Kidney Disease (CRISP) cohort. A biomarker-based classifier consisting of 20 urinary peptides allowed the prediction of ESRD within 10-13 years of follow-up in patients 24-46 years of age at baseline. The performance of the biomarker score approached that of height-adjusted total kidney volume (htTKV) and the combination of the biomarker panel with htTKV improved prediction over either one alone. In young patients (<24 years at baseline), the same biomarker model predicted a 30 mL/min/1.73 m 2 glomerular filtration rate decline over 8 years. Sequence analysis of the altered urinary peptides and the prediction of the involved proteases by in silico analysis revealed alterations in distinct proteolytic pathways, in particular matrix metalloproteinases and cathepsins. We developed a urinary test that accurately predicts relevant clinical outcomes in ADPKD patients and suggests altered proteolytic pathways involved in disease progression. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

The New Neurobiology of Autism

PubMed Central

Minshew, Nancy J.; Williams, Diane L.

2008-01-01

This review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism. PMID:17620483

Predicting Responsiveness to Treatment of Children with Autism: A Retrospective Study of the Importance of Physical Dysmorphology

ERIC Educational Resources Information Center

Stoelb, M.; Yarnal, R.; Miles, J.; Takahashi, T. N.; Farmer, J. E.; McCathren, R. B.

2004-01-01

This retrospective study examined predictors of outcome for children with autism following 6 and 12 months of early intensive behavioral intervention. Potential predictor variables included pretreatment functioning, age at onset of treatment, treatment intensity, family involvement, and physical characteristics (e.g., brain abnormalities,…

The Effects of Labels on Learning Subgoals for Solving Problems.

ERIC Educational Resources Information Center

Catrambone, Richard

This study, involving 65 undergraduates at the Georgia Institute of Technology (Atlanta); explores a scheme for representing problem-solving knowledge and predicting transfer as a function of problem-solving subgoals acquired from examples. A subgoal is an unknown entity (numerical or conceptual) that needs to be found in order to achieve a higher…

Genome-Wide Prediction of Intrinsic Disorder; Sequence Alignment of Intrinsically Disordered Proteins

ERIC Educational Resources Information Center

Midic, Uros

2012-01-01

Intrinsic disorder (ID) is defined as a lack of stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) are highly abundant in nature. IDPs possess a number of crucial biological functions, being involved in regulation, recognition, signaling and control, e.g. their functional…

Evaluation of Short-Term Bioassays to Predict Functional Impairment. Selected Short-Term Renal Toxicity Tests.

DTIC Science & Technology

1980-10-01

reported using the method of Gentzkow (1942), which involves conversion of urea to ammonia with urease and measurement of the ammonia by...Nesslerization. Methods employing urease are not well suited for automated analysis since an incubation time of about 20 minutes is required for the conversion of

Mediators and Moderators of Outcome in the Behavioral Treatment of Childhood Social Phobia

ERIC Educational Resources Information Center

Alfano, Candica A.; Pina, Armando A.; Villalta, Ian K.; Beidel, Deborah C.; Ammerman, Robert T.; Crosby, Lori E.

2009-01-01

Data from a study involving 88 youths who participated in one of two randomized controlled treatment trials of Social Effectiveness Therapy for Children reveals that loneliness scores and social effectiveness predicted changes in social anxiety and overall functioning after the treatment. Child-reported loneliness mediated changes in social…

Predicting the stability of ternary intermetallics with density functional theory and machine learning

NASA Astrophysics Data System (ADS)

Schmidt, Jonathan; Chen, Liming; Botti, Silvana; Marques, Miguel A. L.

2018-06-01

We use a combination of machine learning techniques and high-throughput density-functional theory calculations to explore ternary compounds with the AB2C2 composition. We chose the two most common intermetallic prototypes for this composition, namely, the tI10-CeAl2Ga2 and the tP10-FeMo2B2 structures. Our results suggest that there may be ˜10 times more stable compounds in these phases than previously known. These are mostly metallic and non-magnetic. While the use of machine learning reduces the overall calculation cost by around 75%, some limitations of its predictive power still exist, in particular, for compounds involving the second-row of the periodic table or magnetic elements.

Predicting gene regulatory networks by combining spatial and temporal gene expression data in Arabidopsis root stem cells

PubMed Central

de Luis Balaguer, Maria Angels; Fisher, Adam P.; Clark, Natalie M.; Fernandez-Espinosa, Maria Guadalupe; Möller, Barbara K.; Weijers, Dolf; Williams, Cranos; Lorenzo, Oscar; Sozzani, Rosangela

2017-01-01

Identifying the transcription factors (TFs) and associated networks involved in stem cell regulation is essential for understanding the initiation and growth of plant tissues and organs. Although many TFs have been shown to have a role in the Arabidopsis root stem cells, a comprehensive view of the transcriptional signature of the stem cells is lacking. In this work, we used spatial and temporal transcriptomic data to predict interactions among the genes involved in stem cell regulation. To accomplish this, we transcriptionally profiled several stem cell populations and developed a gene regulatory network inference algorithm that combines clustering with dynamic Bayesian network inference. We leveraged the topology of our networks to infer potential major regulators. Specifically, through mathematical modeling and experimental validation, we identified PERIANTHIA (PAN) as an important molecular regulator of quiescent center function. The results presented in this work show that our combination of molecular biology, computational biology, and mathematical modeling is an efficient approach to identify candidate factors that function in the stem cells. PMID:28827319

Binding Leverage as a Molecular Basis for Allosteric Regulation

PubMed Central

Mitternacht, Simon; Berezovsky, Igor N.

2011-01-01

Allosteric regulation involves conformational transitions or fluctuations between a few closely related states, caused by the binding of effector molecules. We introduce a quantity called binding leverage that measures the ability of a binding site to couple to the intrinsic motions of a protein. We use Monte Carlo simulations to generate potential binding sites and either normal modes or pairs of crystal structures to describe relevant motions. We analyze single catalytic domains and multimeric allosteric enzymes with complex regulation. For the majority of the analyzed proteins, we find that both catalytic and allosteric sites have high binding leverage. Furthermore, our analysis of the catabolite activator protein, which is allosteric without conformational change, shows that its regulation involves other types of motion than those modulated at sites with high binding leverage. Our results point to the importance of incorporating dynamic information when predicting functional sites. Because it is possible to calculate binding leverage from a single crystal structure it can be used for characterizing proteins of unknown function and predicting latent allosteric sites in any protein, with implications for drug design. PMID:21935347

Emotion suppression moderates the quadratic association between RSA and executive function.

PubMed

Spangler, Derek P; Bell, Martha Ann; Deater-Deckard, Kirby

2015-09-01

There is uncertainty about whether respiratory sinus arrhythmia (RSA), a cardiac marker of adaptive emotion regulation, is involved in relatively low or high executive function performance. In the present study, we investigated (a) whether RSA during rest and tasks predict both relatively low and high executive function within a larger quadratic association among the two variables, and (b) the extent to which this quadratic trend was moderated by individual differences in emotion regulation. To achieve these aims, a sample of ethnically and socioeconomically diverse women self-reported reappraisal and emotion suppression. They next experienced a 2-min resting period during which electrocardiogram (ECG) was continually assessed. In the next phase, the women completed an array of executive function and nonexecutive cognitive tasks while ECG was measured throughout. As anticipated, resting RSA showed a quadratic association with executive function that was strongest for high suppression. These results suggest that relatively high resting RSA may predict poor executive function ability when emotion regulation consumes executive control resources needed for ongoing cognitive performance. © 2015 Society for Psychophysiological Research.

A simple attention test in the acute phase of a major depressive episode is predictive of later functional remission.

PubMed

Cléry-Melin, Marie-Laure; Gorwood, Philip

2017-02-01

Functional recovery after a major depressive episode (MDE) requires both clinical remission and preservation of cognitive skills. As attentional deficit may persist after remission, leading to functional impairment, its role as a prognosis marker needs to be considered. Five hundred eight depressed outpatients (DSM-IV) were assessed at baseline for clinical symptoms (QIDS-SR), social functioning (Sheehan Disability Scale, SDS) and attention through the d2 test of attention and the trail making test, simple tests, respectively, requiring to quote or to interconnect relevant items. All patients were treated by agomelatine, and examined 6 to 8 weeks after baseline to assess clinical remission (QIDS-SR ≤ 5) and/or functional remission (SDS ≤ 6). At follow up, 154 patients (31%) were in clinical and functional remission. Shorter cumulative duration of prior depression, shorter present MDE, and two parameters of the d2 test of attention were predictive of such positive outcome, the number of omission mistakes (F1) being the only one still significantly predictive (P < .05) with a multivariate approach. F1 was unchanged after remission, patients with less than 11 mistakes had a 2.27 times increased chance to reach full remission, and a dose-response relationship was observed, with a regular increase of positive outcome for less mistakes. The number of omission mistakes (F1) of the d2 test of attention was a stable marker, being predictive of, and with a dose-effect for, clinical plus functional remission. It may constitute a specific marker of attentional deficit, involved in the resilience process that enables individuals to develop more adequate strategies to cope with everyday functional activities. © 2016 Wiley Periodicals, Inc.

The vacuole system is a significant intracellular pathway for longitudinal solute transport in basidiomycete fungi.

PubMed

Darrah, P R; Tlalka, M; Ashford, A; Watkinson, S C; Fricker, M D

2006-07-01

Mycelial fungi have a growth form which is unique among multicellular organisms. The data presented here suggest that they have developed a unique solution to internal solute translocation involving a complex, extended vacuole. In all filamentous fungi examined, this extended vacuole forms an interconnected network, dynamically linked by tubules, which has been hypothesized to act as an internal distribution system. We have tested this hypothesis directly by quantifying solute movement within the organelle by photobleaching a fluorescent vacuolar marker. Predictive simulation models were then used to determine the transport characteristics over extended length scales. This modeling showed that the vacuolar organelle forms a functionally important, bidirectional diffusive transport pathway over distances of millimeters to centimeters. Flux through the pathway is regulated by the dynamic tubular connections involving homotypic fusion and fission. There is also a strongly predicted interaction among vacuolar organization, predicted diffusion transport distances, and the architecture of the branching colony margin.

"We Are in This Together": Common Group Identity Predicts Majority Members' Active Acculturation Efforts to Integrate Immigrants.

PubMed

Kunst, Jonas R; Thomsen, Lotte; Sam, David L; Berry, John W

2015-10-01

Although integration involves a process of mutual accommodation, the role of majority groups is often downplayed to passive tolerance, leaving immigrants with the sole responsibility for active integration. However, we show that common group identity can actively involve majority members in this process across five studies. Study 1 showed that common identity positively predicted support of integration efforts; Studies 2 and 3 extended these findings, showing that it also predicted real behavior such as monetary donations and volunteering. A decrease in modern racism mediated the relations across these studies, and Studies 4 and 5 further demonstrated that it indeed mediated these effects over and above acculturation expectations and color-blindness, which somewhat compromised integration efforts. Moreover, the last two studies also demonstrated that common, but not dual, groups motivated integration efforts. Common identity appears crucial for securing majorities' altruistic efforts to integrate immigrants and, thus, for achieving functional multiculturalism. © 2015 by the Society for Personality and Social Psychology, Inc.

Functional recovery patterns in seriously injured automotive crash victims.

PubMed

McMurry, Timothy L; Poplin, Gerald S; Crandall, Jeff

2016-09-01

The functional capacity index (FCI) is designed to predict functional loss 12 months post-injury for each injury in the 2008 Abbreviated Injury Scale (AIS) manual on a scale from 0 (death) to 100 (full recovery), but FCI has never been validated. This study compared FCI predicted loss with patient-reported 12-month outcomes as measured through the Short Form 36 (SF-36) health assessment survey. Using follow-up data collected on 2,858 adult car crash occupants in the Crash Injury Research and Engineering Network (CIREN) database, we compared FCI predicted outcomes to occupants' Physical Component Summary (PCS) scores, which are weighted averages of the SF-36 items addressing physical function. Our analyses included descriptive statistics, plots of typical recovery patterns, and a mixed effects regression model that describes PCS as a function of FCI, demographics, comorbidities, and injury pattern while also adjusting for the occupants' pre-crash physical capabilities. We further examined injuries in patients who report a significant drop in PCS 12 months post-crash despite being predicted to fully recover. At baseline, the CIREN population exhibited PCS scores similar to the overall population (mean = 51.1, SD = 10.3). Twelve months post-crash, occupants with predicted impairment (FCI < 100) report a substantial decrease in physical function, and those who were predicted to fully recover still report some, albeit less, impairment. In the multivariate mixed-effects regression model, FCI is a strongly significant (P-value <.0001) predictor of PCS, with each 1-point drop in FCI predicting a 0.27-point drop in PCS. Maximum AIS severities in the head, spine, and lower extremity body regions were also significantly associated with PCS (P-values <.05). Among occupants who were expected to fully recover but who report a significant drop in PCS at 12 months, spinal fractures without cord involvement account for 5 of the 10 most common AIS 2+ injuries. FCI was associated with 12-month outcomes but may not adequately describe the recovery from some head, spine, and lower extremity injuries. Some occupants who were expected to recover still report functional loss 12 months post-injury.

Is parents' work involvement responsive to the quality of relationships with adolescent offspring?

PubMed

Fortner, Melissa R; Crouter, Ann C; McHale, Susan M

2004-09-01

Researchers know relatively little about how family relationships influence work involvement, although individuals are concerned about how family life interferes with or enhances work experiences. This study examined change in parents' work involvement as a function of relationship quality with offspring (mean age = 15 years) with data from 191 families participating in a longitudinal study. Results suggested a compensatory association between parents' feelings of acceptance and warmth toward offspring and work involvement. Less positive acceptance predicted (a) increasing emotional job involvement for mothers with sons and fathers with daughters and (b) increasing work hours for fathers with daughters. Results highlight how parents may compensate for less positive relationships with adolescents and are discussed in terms of research and applied implications. Copyright 2004 American Psychological Association

Elastic network model of learned maintained contacts to predict protein motion

PubMed Central

Putz, Ines

2017-01-01

We present a novel elastic network model, lmcENM, to determine protein motion even for localized functional motions that involve substantial changes in the protein’s contact topology. Existing elastic network models assume that the contact topology remains unchanged throughout the motion and are thus most appropriate to simulate highly collective function-related movements. lmcENM uses machine learning to differentiate breaking from maintained contacts. We show that lmcENM accurately captures functional transitions unexplained by the classical ENM and three reference ENM variants, while preserving the simplicity of classical ENM. We demonstrate the effectiveness of our approach on a large set of proteins covering different motion types. Our results suggest that accurately predicting a “deformation-invariant” contact topology offers a promising route to increase the general applicability of ENMs. We also find that to correctly predict this contact topology a combination of several features seems to be relevant which may vary slightly depending on the protein. Additionally, we present case studies of two biologically interesting systems, Ferric Citrate membrane transporter FecA and Arachidonate 15-Lipoxygenase. PMID:28854238

Functional connectivity between the cerebrum and cerebellum in social cognition: A multi-study analysis.

PubMed

Van Overwalle, Frank; Mariën, Peter

2016-01-01

This multi-study connectivity analysis explores the functional connectivity of the cerebellum with the cerebrum in social mentalizing, that is, understanding the mind of another person. The analysis covers 5 studies (n=92) involving abstract and complex forms of social mentalizing such as (a) person and group impression formation based on behavioral descriptions and (b) constructing personal counterfactual events (i.e., how the past could have turned out better). The results suggest that cerebellar activity during these social processes reflects a domain-specific mentalizing functionality that is strongly connected with a corresponding mentalizing network in the cerebrum. A significant pattern of connectivity was found linking the dorsal medial prefrontal cortex (mPFC) and the right temporo-parietal junction (TPJ) with the right posterior cerebellum, and linking the latter with the left TPJ. In addition, in the cerebrum, further connectivity was found through links of the bilateral TPJ with the dorsal mPFC, orbitofrontal cortex and between right and left TPJ. The discussion centers on the role of these cerebro-cerebellar connections in matching external information from the cerebrum with internal predictions generated by the cerebellum. These internal predictions might involve the sequencing of the person's behaviors. Copyright © 2015 Elsevier Inc. All rights reserved.

The Developmental Costs and Benefits of Children’s Involvement in Interparental Conflict

PubMed Central

Davies, Patrick T.; Coe, Jesse L.; Martin, Meredith J.; Sturge-Apple, Melissa L.; Cummings, E. Mark

2015-01-01

Building on empirical documentation of children’s involvement in interparental conflicts as a weak predictor of psychopathology, we tested the hypothesis that involvement in conflict more consistently serves as a moderator of associations between children’s emotional reactivity to interparental conflict and their psychological problems. In Study 1, 263 early adolescents (M age = 12.62 years), mothers, and fathers completed surveys of family and child functioning at two measurement occasions spaced two years apart. In Study 2, 243 preschool children (M age = 4.60 years) participated in a multi-method (i.e., observations, structured interview, surveys) measurement battery to assess family functioning, children’s reactivity to interparental conflict, and their psychological adjustment. Across both studies, latent difference score (LDS) analyses revealed that involvement moderated associations between emotional reactivity and children’s increases in psychological (i.e., internalizing and externalizing) problems. Children’s emotional reactivity to interparental conflict was a significantly stronger predictor of their psychological maladjustment when they were highly involved in the conflicts. In addition, the developmental benefits and costs of involvement varied as a function of emotional reactivity. Involvement in interparental conflict predicted increases in psychological problems for children experiencing high emotional reactivity and decreases in psychological problems when they exhibited low emotional reactivity. We interpret the results in the context of the new formulation of emotional security theory (e.g. Davies & Martin, 2013) and family systems models of children’s parentification (e.g., Byng-Hall, 2002). PMID:26053147

The developmental costs and benefits of children's involvement in interparental conflict.

PubMed

Davies, Patrick T; Coe, Jesse L; Martin, Meredith J; Sturge-Apple, Melissa L; Cummings, E Mark

2015-08-01

Building on empirical documentation of children's involvement in interparental conflicts as a weak predictor of psychopathology, we tested the hypothesis that involvement in conflict more consistently serves as a moderator of associations between children's emotional reactivity to interparental conflict and their psychological problems. In Study 1, 263 early adolescents (M age = 12.62 years), mothers, and fathers completed surveys of family and child functioning at 2 measurement occasions spaced 2 years apart. In Study 2, 243 preschool children (M age = 4.60 years) participated in a multimethod (i.e., observations, structured interview, surveys) measurement battery to assess family functioning, children's reactivity to interparental conflict, and their psychological adjustment. Across both studies, latent difference score analyses revealed that involvement moderated associations between emotional reactivity and children's increases in psychological (i.e., internalizing and externalizing) problems. Children's emotional reactivity to interparental conflict was a significantly stronger predictor of their psychological maladjustment when they were highly involved in the conflicts. In addition, the developmental benefits and costs of involvement varied as a function of emotional reactivity. Involvement in interparental conflict predicted increases in psychological problems for children experiencing high emotional reactivity and decreases in psychological problems when they exhibited low emotional reactivity. We interpret the results in the context of the new formulation of emotional security theory (e.g., Davies & Martin, 2013) and family systems models of children's parentification (e.g., Byng-Hall, 2002). (c) 2015 APA, all rights reserved).

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network.

PubMed

Ding, Fangrui; Tan, Aidi; Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies.

The Prediction of Key Cytoskeleton Components Involved in Glomerular Diseases Based on a Protein-Protein Interaction Network

PubMed Central

Ju, Wenjun; Li, Xuejuan; Li, Shao; Ding, Jie

2016-01-01

Maintenance of the physiological morphologies of different types of cells and tissues is essential for the normal functioning of each system in the human body. Dynamic variations in cell and tissue morphologies depend on accurate adjustments of the cytoskeletal system. The cytoskeletal system in the glomerulus plays a key role in the normal process of kidney filtration. To enhance the understanding of the possible roles of the cytoskeleton in glomerular diseases, we constructed the Glomerular Cytoskeleton Network (GCNet), which shows the protein-protein interaction network in the glomerulus, and identified several possible key cytoskeletal components involved in glomerular diseases. In this study, genes/proteins annotated to the cytoskeleton were detected by Gene Ontology analysis, and glomerulus-enriched genes were selected from nine available glomerular expression datasets. Then, the GCNet was generated by combining these two sets of information. To predict the possible key cytoskeleton components in glomerular diseases, we then examined the common regulation of the genes in GCNet in the context of five glomerular diseases based on their transcriptomic data. As a result, twenty-one cytoskeleton components as potential candidate were highlighted for consistently down- or up-regulating in all five glomerular diseases. And then, these candidates were examined in relation to existing known glomerular diseases and genes to determine their possible functions and interactions. In addition, the mRNA levels of these candidates were also validated in a puromycin aminonucleoside(PAN) induced rat nephropathy model and were also matched with existing Diabetic Nephropathy (DN) transcriptomic data. As a result, there are 15 of 21 candidates in PAN induced nephropathy model were consistent with our predication and also 12 of 21 candidates were matched with differentially expressed genes in the DN transcriptomic data. By providing a novel interaction network and prediction, GCNet contributes to improving the understanding of normal glomerular function and will be useful for detecting target cytoskeleton molecules of interest that may be involved in glomerular diseases in future studies. PMID:27227331

Extinction vulnerability of coral reef fishes.

PubMed

Graham, Nicholas A J; Chabanet, Pascale; Evans, Richard D; Jennings, Simon; Letourneur, Yves; Aaron Macneil, M; McClanahan, Tim R; Ohman, Marcus C; Polunin, Nicholas V C; Wilson, Shaun K

2011-04-01

With rapidly increasing rates of contemporary extinction, predicting extinction vulnerability and identifying how multiple stressors drive non-random species loss have become key challenges in ecology. These assessments are crucial for avoiding the loss of key functional groups that sustain ecosystem processes and services. We developed a novel predictive framework of species extinction vulnerability and applied it to coral reef fishes. Although relatively few coral reef fishes are at risk of global extinction from climate disturbances, a negative convex relationship between fish species locally vulnerable to climate change vs. fisheries exploitation indicates that the entire community is vulnerable on the many reefs where both stressors co-occur. Fishes involved in maintaining key ecosystem functions are more at risk from fishing than climate disturbances. This finding is encouraging as local and regional commitment to fisheries management action can maintain reef ecosystem functions pending progress towards the more complex global problem of stabilizing the climate. © 2011 Blackwell Publishing Ltd/CNRS.

Propagation of a radio-frequency pulsed signal over the Earth. The JOLLY programs

NASA Astrophysics Data System (ADS)

Carroll, D.; Detch, J. L.; Malik, J.

1983-07-01

The interpretation of observed radioflash/electromagnetic pulse (emp) observed signals from nuclear detonations in terms of theoretical models or extrapolation to signals expected at military systems involves correction for ground-wave propagation effects. For most applications, previously developed programs have been adequate. There have been problems when these techniques have been tried for situations in the near tangent regime where a considerable concern exists. It has been found that the problem of predicting propagation response functions in the near tangent regime has been the inconsistent derivation of the equations. Resolution of this problem has evolved into a program to better predict ground-wave propagation. The description of the method and detailed description of the programs are described for both propagation over realistic earth and sea-water paths. Results can be given in terms of amplitude and phase as a function of the frequency or as amplitude versus time, the usual Green's or resolution function.

From plant traits to plant communities: a statistical mechanistic approach to biodiversity.

PubMed

Shipley, Bill; Vile, Denis; Garnier, Eric

2006-11-03

We developed a quantitative method, analogous to those used in statistical mechanics, to predict how biodiversity will vary across environments, which plant species from a species pool will be found in which relative abundances in a given environment, and which plant traits determine community assembly. This provides a scaling from plant traits to ecological communities while bypassing the complications of population dynamics. Our method treats community development as a sorting process involving species that are ecologically equivalent except with respect to particular functional traits, which leads to a constrained random assembly of species; the relative abundance of each species adheres to a general exponential distribution as a function of its traits. Using data for eight functional traits of 30 herbaceous species and community-aggregated values of these traits in 12 sites along a 42-year chronosequence of secondary succession, we predicted 94% of the variance in the relative abundances.

Extinction vulnerability of coral reef fishes

PubMed Central

Graham, Nicholas A J; Chabanet, Pascale; Evans, Richard D; Jennings, Simon; Letourneur, Yves; Aaron MacNeil, M; McClanahan, Tim R; Öhman, Marcus C; Polunin, Nicholas V C; Wilson, Shaun K

2011-01-01

With rapidly increasing rates of contemporary extinction, predicting extinction vulnerability and identifying how multiple stressors drive non-random species loss have become key challenges in ecology. These assessments are crucial for avoiding the loss of key functional groups that sustain ecosystem processes and services. We developed a novel predictive framework of species extinction vulnerability and applied it to coral reef fishes. Although relatively few coral reef fishes are at risk of global extinction from climate disturbances, a negative convex relationship between fish species locally vulnerable to climate change vs. fisheries exploitation indicates that the entire community is vulnerable on the many reefs where both stressors co-occur. Fishes involved in maintaining key ecosystem functions are more at risk from fishing than climate disturbances. This finding is encouraging as local and regional commitment to fisheries management action can maintain reef ecosystem functions pending progress towards the more complex global problem of stabilizing the climate. PMID:21320260

Predicting PDZ domain mediated protein interactions from structure

PubMed Central

2013-01-01

Background PDZ domains are structural protein domains that recognize simple linear amino acid motifs, often at protein C-termini, and mediate protein-protein interactions (PPIs) in important biological processes, such as ion channel regulation, cell polarity and neural development. PDZ domain-peptide interaction predictors have been developed based on domain and peptide sequence information. Since domain structure is known to influence binding specificity, we hypothesized that structural information could be used to predict new interactions compared to sequence-based predictors. Results We developed a novel computational predictor of PDZ domain and C-terminal peptide interactions using a support vector machine trained with PDZ domain structure and peptide sequence information. Performance was estimated using extensive cross validation testing. We used the structure-based predictor to scan the human proteome for ligands of 218 PDZ domains and show that the predictions correspond to known PDZ domain-peptide interactions and PPIs in curated databases. The structure-based predictor is complementary to the sequence-based predictor, finding unique known and novel PPIs, and is less dependent on training–testing domain sequence similarity. We used a functional enrichment analysis of our hits to create a predicted map of PDZ domain biology. This map highlights PDZ domain involvement in diverse biological processes, some only found by the structure-based predictor. Based on this analysis, we predict novel PDZ domain involvement in xenobiotic metabolism and suggest new interactions for other processes including wound healing and Wnt signalling. Conclusions We built a structure-based predictor of PDZ domain-peptide interactions, which can be used to scan C-terminal proteomes for PDZ interactions. We also show that the structure-based predictor finds many known PDZ mediated PPIs in human that were not found by our previous sequence-based predictor and is less dependent on training–testing domain sequence similarity. Using both predictors, we defined a functional map of human PDZ domain biology and predict novel PDZ domain function. Users may access our structure-based and previous sequence-based predictors at http://webservice.baderlab.org/domains/POW. PMID:23336252

Identification of functional candidates amongst hypothetical proteins of Mycobacterium leprae Br4923, a causative agent of leprosy.

PubMed

Naqvi, Ahmad Abu Turab; Ahmad, Faizan; Hassan, Md Imtaiyaz

2015-01-01

Mycobacterium leprae is an intracellular obligate parasite that causes leprosy in humans, and it leads to the destruction of peripheral nerves and skin deformation. Here, we report an extensive analysis of the hypothetical proteins (HPs) from M. leprae strain Br4923, assigning their functions to better understand the mechanism of pathogenesis and to search for potential therapeutic interventions. The genome of M. leprae encodes 1604 proteins, of which the functions of 632 are not known (HPs). In this paper, we predicted the probable functions of 312 HPs. First, we classified all HPs into families and subfamilies on the basis of sequence similarity, followed by domain assignment, which provides many clues for their possible function. However, the functions of 320 proteins were not predicted because of low sequence similarity with proteins of known function. Annotated HPs were categorized into enzymes, binding proteins, transporters, and proteins involved in cellular processes. We found several novel proteins whose functions were unknown for M. leprae. These proteins have a requisite association with bacterial virulence and pathogenicity. Finally, our sequence-based analysis will be helpful for further validation and the search for potential drug targets while developing effective drugs to cure leprosy.

Acetone utilization by sulfate-reducing bacteria: draft genome sequence of Desulfococcus biacutus and a proteomic survey of acetone-inducible proteins.

PubMed

Gutiérrez Acosta, Olga B; Schleheck, David; Schink, Bernhard

2014-07-11

The sulfate-reducing bacterium Desulfococcus biacutus is able to utilize acetone for growth by an inducible degradation pathway that involves a novel activation reaction for acetone with CO as a co-substrate. The mechanism, enzyme(s) and gene(s) involved in this acetone activation reaction are of great interest because they represent a novel and yet undefined type of activation reaction under strictly anoxic conditions. In this study, a draft genome sequence of D. biacutus was established. Sequencing, assembly and annotation resulted in 159 contigs with 5,242,029 base pairs and 4773 predicted genes; 4708 were predicted protein-encoding genes, and 3520 of these had a functional prediction. Proteins and genes were identified that are specifically induced during growth with acetone. A thiamine diphosphate-requiring enzyme appeared to be highly induced during growth with acetone and is probably involved in the activation reaction. Moreover, a coenzyme B12- dependent enzyme and proteins that are involved in redox reactions were also induced during growth with acetone. We present for the first time the genome of a sulfate reducer that is able to grow with acetone. The genome information of this organism represents an important tool for the elucidation of a novel reaction mechanism that is employed by a sulfate reducer in acetone activation.

Bioinformatics approaches for structural and functional analysis of proteins in secondary metabolism in Withania somnifera.

PubMed

Sanchita; Singh, Swati; Sharma, Ashok

2014-11-01

Withania somnifera (Ashwagandha) is an affluent storehouse of large number of pharmacologically active secondary metabolites known as withanolides. These secondary metabolites are produced by withanolide biosynthetic pathway. Very less information is available on structural and functional aspects of enzymes involved in withanolides biosynthetic pathways of Withiana somnifera. We therefore performed a bioinformatics analysis to look at functional and structural properties of these important enzymes. The pathway enzymes taken for this study were 3-Hydroxy-3-methylglutaryl coenzyme A reductase, 1-Deoxy-D-xylulose-5-phosphate synthase, 1-Deoxy-D-xylulose-5-phosphate reductase, farnesyl pyrophosphate synthase, squalene synthase, squalene epoxidase, and cycloartenol synthase. The prediction of secondary structure was performed for basic structural information. Three-dimensional structures for these enzymes were predicted. The physico-chemical properties such as pI, AI, GRAVY and instability index were also studied. The current information will provide a platform to know the structural attributes responsible for the function of these protein until experimental structures become available.

Crystal structure optimisation using an auxiliary equation of state

NASA Astrophysics Data System (ADS)

Jackson, Adam J.; Skelton, Jonathan M.; Hendon, Christopher H.; Butler, Keith T.; Walsh, Aron

2015-11-01

Standard procedures for local crystal-structure optimisation involve numerous energy and force calculations. It is common to calculate an energy-volume curve, fitting an equation of state around the equilibrium cell volume. This is a computationally intensive process, in particular, for low-symmetry crystal structures where each isochoric optimisation involves energy minimisation over many degrees of freedom. Such procedures can be prohibitive for non-local exchange-correlation functionals or other "beyond" density functional theory electronic structure techniques, particularly where analytical gradients are not available. We present a simple approach for efficient optimisation of crystal structures based on a known equation of state. The equilibrium volume can be predicted from one single-point calculation and refined with successive calculations if required. The approach is validated for PbS, PbTe, ZnS, and ZnTe using nine density functionals and applied to the quaternary semiconductor Cu2ZnSnS4 and the magnetic metal-organic framework HKUST-1.

Hierarchical Learning Induces Two Simultaneous, But Separable, Prediction Errors in Human Basal Ganglia

PubMed Central

Tsai, Karin; Wallis, Jonathan; Botvinick, Matthew

2013-01-01

Studies suggest that dopaminergic neurons report a unitary, global reward prediction error signal. However, learning in complex real-life tasks, in particular tasks that show hierarchical structure, requires multiple prediction errors that may coincide in time. We used functional neuroimaging to measure prediction error signals in humans performing such a hierarchical task involving simultaneous, uncorrelated prediction errors. Analysis of signals in a priori anatomical regions of interest in the ventral striatum and the ventral tegmental area indeed evidenced two simultaneous, but separable, prediction error signals corresponding to the two levels of hierarchy in the task. This result suggests that suitably designed tasks may reveal a more intricate pattern of firing in dopaminergic neurons. Moreover, the need for downstream separation of these signals implies possible limitations on the number of different task levels that we can learn about simultaneously. PMID:23536092

Computing wave functions in multichannel collisions with non-local potentials using the R-matrix method

NASA Astrophysics Data System (ADS)

Bonitati, Joey; Slimmer, Ben; Li, Weichuan; Potel, Gregory; Nunes, Filomena

2017-09-01

The calculable form of the R-matrix method has been previously shown to be a useful tool in approximately solving the Schrodinger equation in nuclear scattering problems. We use this technique combined with the Gauss quadrature for the Lagrange-mesh method to efficiently solve for the wave functions of projectile nuclei in low energy collisions (1-100 MeV) involving an arbitrary number of channels. We include the local Woods-Saxon potential, the non-local potential of Perey and Buck, a Coulomb potential, and a coupling potential to computationally solve for the wave function of two nuclei at short distances. Object oriented programming is used to increase modularity, and parallel programming techniques are introduced to reduce computation time. We conclude that the R-matrix method is an effective method to predict the wave functions of nuclei in scattering problems involving both multiple channels and non-local potentials. Michigan State University iCER ACRES REU.

Near-death experiences and the temporal lobe.

PubMed

Britton, Willoughby B; Bootzin, Richard R

2004-04-01

Many studies in humans suggest that altered temporal lobe functioning, especially functioning in the right temporal lobe, is involved in mystical and religious experiences. We investigated temporal lobe functioning in individuals who reported having transcendental "near-death experiences" during life-threatening events. These individuals were found to have more temporal lobe epileptiform electroencephalographic activity than control subjects and also reported significantly more temporal lobe epileptic symptoms. Contrary to predictions, epileptiform activity was nearly completely lateralized to the left hemisphere. The near-death experience was not associated with dysfunctional stress reactions such as dissociation, posttraumatic stress disorder, and substance abuse, but rather was associated with positive coping styles. Additional analyses revealed that near-death experiencers had altered sleep patterns, specifically, a shorter duration of sleep and delayed REM sleep relative to the control group. These results suggest that altered temporal lobe functioning may be involved in the near-death experience and that individuals who have had such experiences are physiologically distinct from the general population.

A genome-wide analysis of the flax (Linum usitatissimum L.) dirigent protein family: from gene identification and evolution to differential regulation

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

Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija

Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset ofmore » genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.« less

A genome-wide analysis of the flax (Linum usitatissimum L.) dirigent protein family: from gene identification and evolution to differential regulation.

PubMed

Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija; Auguin, Daniel; Lainé, Éric; Davin, Laurence B; Cort, John R; Lewis, Norman G; Hano, Christophe

2018-05-01

Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset of genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence.

PubMed

Chang, Andrew; Bosnyak, Dan J; Trainor, Laurel J

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15-25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15-20 Hz) was larger around 200-300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both "when" (timing) upcoming sounds will occur as well as the prediction precision error of "what" (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception.

Unpredicted Pitch Modulates Beta Oscillatory Power during Rhythmic Entrainment to a Tone Sequence

PubMed Central

Chang, Andrew; Bosnyak, Dan J.; Trainor, Laurel J.

2016-01-01

Extracting temporal regularities in external stimuli in order to predict upcoming events is an essential aspect of perception. Fluctuations in induced power of beta band (15–25 Hz) oscillations in auditory cortex are involved in predictive timing during rhythmic entrainment, but whether such fluctuations are affected by prediction in the spectral (frequency/pitch) domain remains unclear. We tested whether unpredicted (i.e., unexpected) pitches in a rhythmic tone sequence modulate beta band activity by recording EEG while participants passively listened to isochronous auditory oddball sequences with occasional unpredicted deviant pitches at two different presentation rates. The results showed that the power in low-beta (15–20 Hz) was larger around 200–300 ms following deviant tones compared to standard tones, and this effect was larger when the deviant tones were less predicted. Our results suggest that the induced beta power activities in auditory cortex are consistent with a role in sensory prediction of both “when” (timing) upcoming sounds will occur as well as the prediction precision error of “what” (spectral content in this case). We suggest, further, that both timing and content predictions may co-modulate beta oscillations via attention. These findings extend earlier work on neural oscillations by investigating the functional significance of beta oscillations for sensory prediction. The findings help elucidate the functional significance of beta oscillations in perception. PMID:27014138

A Growth and Yield Model for Thinned Stands of Yellow-Poplar

Treesearch

Bruce R. Knoebel; Harold E. Burkhart; Donald E. Beck

1986-01-01

Simultaneous growth and yield equations were developed for predicting basal area growth and cubic-foot volume growth and yield in thinned stands of yellow-poplar. A joint loss function involving both volume and basal area was used to estimate the coefficients in the system of equations. The estimates obtained were analytically compatible, invariant for projection...

Structure Prediction of Protein Complexes

NASA Astrophysics Data System (ADS)

Pierce, Brian; Weng, Zhiping

Protein-protein interactions are critical for biological function. They directly and indirectly influence the biological systems of which they are a part. Antibodies bind with antigens to detect and stop viruses and other infectious agents. Cell signaling is performed in many cases through the interactions between proteins. Many diseases involve protein-protein interactions on some level, including cancer and prion diseases.

Predicting Suicide Risks among Outpatient Adolescents Using the Family Environment Scale: Implications for Practice and Research

ERIC Educational Resources Information Center

Lucey, Christopher F.; Lam, Sarah K. Y.

2012-01-01

This study was designed to identify characteristics of family functioning that relate to suicide potential in an outpatient adolescent population. Participants included 51 adolescents between the ages of 14 and 18 who were involved in outpatient counselling. The Family Environment Scale and the Suicide Probability Scale were used to assess…

Validity of Sudden Gains in Acute Phase Treatment of Depression

ERIC Educational Resources Information Center

Vittengl, Jeffrey R.; Clark, Lee Anna; Jarrett, Robin B.

2005-01-01

The authors examined the validity of sudden gains identified with T. Z. Tang and R. J. DeRubeis's (1999) method in 2 clinical data sets that involved treatment of major depressive disorder (N=227). Sudden gains replicated among self- and clinician reports of depressive symptoms and predicted better psychosocial functioning at the acute phase…

Improving Prediction Accuracy for WSN Data Reduction by Applying Multivariate Spatio-Temporal Correlation

PubMed Central

Carvalho, Carlos; Gomes, Danielo G.; Agoulmine, Nazim; de Souza, José Neuman

2011-01-01

This paper proposes a method based on multivariate spatial and temporal correlation to improve prediction accuracy in data reduction for Wireless Sensor Networks (WSN). Prediction of data not sent to the sink node is a technique used to save energy in WSNs by reducing the amount of data traffic. However, it may not be very accurate. Simulations were made involving simple linear regression and multiple linear regression functions to assess the performance of the proposed method. The results show a higher correlation between gathered inputs when compared to time, which is an independent variable widely used for prediction and forecasting. Prediction accuracy is lower when simple linear regression is used, whereas multiple linear regression is the most accurate one. In addition to that, our proposal outperforms some current solutions by about 50% in humidity prediction and 21% in light prediction. To the best of our knowledge, we believe that we are probably the first to address prediction based on multivariate correlation for WSN data reduction. PMID:22346626

Fatigue-Related Gene Networks Identified in CD14+ Cells Isolated From HIV-Infected Patients—Part I: Research Findings

PubMed Central

Voss, Joachim G.; Dobra, Adrian; Morse, Caryn; Kovacs, Joseph A.; Danner, Robert L.; Munson, Peter J.; Logan, Carolea; Rangel, Zoila; Adelsberger, Joseph W.; McLaughlin, Mary; Adams, Larry D.; Raju, Raghavan; Dalakas, Marinos C.

2016-01-01

Purpose Human immunodeficiency virus (HIV)–related fatigue (HRF) is multicausal and potentially related to mitochondrial dysfunction caused by antiretroviral therapy with nucleoside reverse transcriptase inhibitors (NRTIs). Methodology The authors compared gene expression profiles of CD14+ cells of low versus high fatigued, NRTI-treated HIV patients to healthy controls (n = 5/group). The authors identified 32 genes predictive of low versus high fatigue and 33 genes predictive of healthy versus HIV infection. The authors constructed genetic networks to further elucidate the possible biological pathways in which these genes are involved. Relevance for nursing practice Genes including the actin cytoskeletal regulatory proteins Prokineticin 2 and Cofilin 2 along with mitochondrial inner membrane proteins are involved in multiple pathways and were predictors of fatigue status. Previously identified inflammatory and signaling genes were predictive of HIV status, clearly confirming our results and suggesting a possible further connection between mitochondrial function and HIV. Isolated CD14+ cells are easily accessible cells that could be used for further study of the connection between fatigue and mitochondrial function of HIV patients. Implication for Practice The findings from this pilot study take us one step closer to identifying biomarker targets for fatigue status and mitochondrial dysfunction. Specific biomarkers will be pertinent to the development of methodologies to diagnosis, monitor, and treat fatigue and mitochondrial dysfunction. PMID:23324479

Stringent DDI-based Prediction of H. sapiens-M. tuberculosis H37Rv Protein-Protein Interactions

PubMed Central

2013-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are very important information to illuminate the infection mechanism of M. tuberculosis H37Rv. But current H. sapiens-M. tuberculosis H37Rv PPI data are very scarce. This seriously limits the study of the interaction between this important pathogen and its host H. sapiens. Computational prediction of H. sapiens-M. tuberculosis H37Rv PPIs is an important strategy to fill in the gap. Domain-domain interaction (DDI) based prediction is one of the frequently used computational approaches in predicting both intra-species and inter-species PPIs. However, the performance of DDI-based host-pathogen PPI prediction has been rather limited. Results We develop a stringent DDI-based prediction approach with emphasis on (i) differences between the specific domain sequences on annotated regions of proteins under the same domain ID and (ii) calculation of the interaction strength of predicted PPIs based on the interacting residues in their interaction interfaces. We compare our stringent DDI-based approach to a conventional DDI-based approach for predicting PPIs based on gold standard intra-species PPIs and coherent informative Gene Ontology terms assessment. The assessment results show that our stringent DDI-based approach achieves much better performance in predicting PPIs than the conventional approach. Using our stringent DDI-based approach, we have predicted a small set of reliable H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. We also analyze the H. sapiens-M. tuberculosis H37Rv PPIs predicted by our stringent DDI-based approach using cellular compartment distribution analysis, functional category enrichment analysis and pathway enrichment analysis. The analyses support the validity of our prediction result. Also, based on an analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent DDI-based approach, we have discovered some important properties of domains involved in host-pathogen PPIs. We find that both host and pathogen proteins involved in host-pathogen PPIs tend to have more domains than proteins involved in intra-species PPIs, and these domains have more interaction partners than domains on proteins involved in intra-species PPI. Conclusions The stringent DDI-based prediction approach reported in this work provides a stringent strategy for predicting host-pathogen PPIs. It also performs better than a conventional DDI-based approach in predicting PPIs. We have predicted a small set of accurate H. sapiens-M. tuberculosis H37Rv PPIs which could be very useful for a variety of related studies. PMID:24564941

Species Diversity and Functional Prediction of Surface Bacterial Communities on Aging Flue-Cured Tobaccos.

PubMed

Wang, Fan; Zhao, Hongwei; Xiang, Haiying; Wu, Lijun; Men, Xiao; Qi, Chang; Chen, Guoqiang; Zhang, Haibo; Wang, Yi; Xian, Mo

2018-06-05

Microbes on aging flue-cured tobaccos (ATFs) improve the aroma and other qualities desirable in products. Understanding the relevant organisms would picture microbial community diversity, metabolic potential, and their applications. However, limited efforts have been made on characterizing the microbial quality and functional profiling. Herein, we present our investigation of the bacterial diversity and predicted potential genetic capability of the bacteria from two AFTs using 16S rRNA gene sequences and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) software. The results show that dominant bacteria from AFT surfaces were classified into 48 genera, 36 families, and 7 phyla. In addition, Bacillus spp. was found prevalent on both ATFs. Furthermore, PICRUSt predictions of bacterial community functions revealed many attractive metabolic capacities in the AFT microbiota, including several involved in the biosynthesis of flavors and fragrances and the degradation of harmful compounds, such as nicotine and nitrite. These results provide insights into the importance of AFT bacteria in determining product qualities and indicate specific microbial species with predicted enzymatic capabilities for the production of high-efficiency flavors, the degradation of undesirable compounds, and the provision of nicotine and nitrite tolerance which suggest fruitful areas of investigation into the manipulation of AFT microbiota for AFT and other product improvements.

Spontaneous brain activity predicts learning ability of foreign sounds.

PubMed

Ventura-Campos, Noelia; Sanjuán, Ana; González, Julio; Palomar-García, María-Ángeles; Rodríguez-Pujadas, Aina; Sebastián-Gallés, Núria; Deco, Gustavo; Ávila, César

2013-05-29

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined.

The University of Minnesota Biocatalysis/Biodegradation Database: specialized metabolism for functional genomics.

PubMed Central

Ellis, L B; Hershberger, C D; Wackett, L P

1999-01-01

The University of Minnesota Biocatalysis/Biodegradation Database (UM-BBD, http://www.labmed.umn.edu/umbbd/i nde x.html) first became available on the web in 1995 to provide information on microbial biocatalytic reactions of, and biodegradation pathways for, organic chemical compounds, especially those produced by man. Its goal is to become a representative database of biodegradation, spanning the diversity of known microbial metabolic routes, organic functional groups, and environmental conditions under which biodegradation occurs. The database can be used to enhance understanding of basic biochemistry, biocatalysis leading to speciality chemical manufacture, and biodegradation of environmental pollutants. It is also a resource for functional genomics, since it contains information on enzymes and genes involved in specialized metabolism not found in intermediary metabolism databases, and thus can assist in assigning functions to genes homologous to such less common genes. With information on >400 reactions and compounds, it is poised to become a resource for prediction of microbial biodegradation pathways for compounds it does not contain, a process complementary to predicting the functions of new classes of microbial genes. PMID:9847233

Toward a better understanding on the role of prediction error on memory processes: From bench to clinic.

PubMed

Krawczyk, María C; Fernández, Rodrigo S; Pedreira, María E; Boccia, Mariano M

2017-07-01

Experimental psychology defines Prediction Error (PE) as a mismatch between expected and current events. It represents a unifier concept within the memory field, as it is the driving force of memory acquisition and updating. Prediction error induces updating of consolidated memories in strength or content by memory reconsolidation. This process has two different neurobiological phases, which involves the destabilization (labilization) of a consolidated memory followed by its restabilization. The aim of this work is to emphasize the functional role of PE on the neurobiology of learning and memory, integrating and discussing different research areas: behavioral, neurobiological, computational and clinical psychiatry. Copyright © 2016 Elsevier Inc. All rights reserved.

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

PubMed

Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun

2009-06-01

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Integration of Structural Dynamics and Molecular Evolution via Protein Interaction Networks: A New Era in Genomic Medicine

PubMed Central

Kumar, Avishek; Butler, Brandon M.; Kumar, Sudhir; Ozkan, S. Banu

2016-01-01

Summary Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. PMID:26684487

Deciphering the ubiquitin-mediated pathway in apicomplexan parasites: a potential strategy to interfere with parasite virulence.

PubMed

Ponts, Nadia; Yang, Jianfeng; Chung, Duk-Won Doug; Prudhomme, Jacques; Girke, Thomas; Horrocks, Paul; Le Roch, Karine G

2008-06-11

Reversible modification of proteins through the attachment of ubiquitin or ubiquitin-like modifiers is an essential post-translational regulatory mechanism in eukaryotes. The conjugation of ubiquitin or ubiquitin-like proteins has been demonstrated to play roles in growth, adaptation and homeostasis in all eukaryotes, with perturbation of ubiquitin-mediated systems associated with the pathogenesis of many human diseases, including cancer and neurodegenerative disorders. Here we describe the use of an HMM search of functional Pfam domains found in the key components of the ubiquitin-mediated pathway necessary to activate and reversibly modify target proteins in eight apicomplexan parasitic protozoa for which complete or late-stage genome projects exist. In parallel, the same search was conducted on five model organisms, single-celled and metazoans, to generate data to validate both the search parameters employed and aid paralog classification in Apicomplexa. For each of the 13 species investigated, a set of proteins predicted to be involved in the ubiquitylation pathway has been identified and demonstrates increasing component members of the ubiquitylation pathway correlating with organism and genome complexity. Sequence homology and domain architecture analyses facilitated prediction of apicomplexan-specific protein function, particularly those involved in regulating cell division during these parasite's complex life cycles. This study provides a comprehensive analysis of proteins predicted to be involved in the apicomplexan ubiquitin-mediated pathway. Given the importance of such pathway in a wide variety of cellular processes, our data is a key step in elucidating the biological networks that, in part, direct the pathogenicity of these parasites resulting in a massive impact on global health. Moreover, apicomplexan-specific adaptations of the ubiquitylation pathway may represent new therapeutic targets for much needed drugs against apicomplexan parasites.

Clinical value of natriuretic peptides in chronic kidney disease.

PubMed

Santos-Araújo, Carla; Leite-Moreira, Adelino; Pestana, Manuel

2015-01-01

According to several lines of evidence, natriuretic peptides (NP) are the main components of a cardiac-renal axis that operate in clinical conditions of decreased cardiac hemodynamic tolerance to regulate sodium homeostasis, blood pressure and vascular function. Even though it is reasonable to assume that NP may exert a relevant role in the adaptive response to renal mass ablation, evidence gathered so far suggest that this contribution is probably complex and dependent on the type and degree of the functional mass loss. In the last years NP have been increasingly used to diagnose, monitor treatment and define the prognosis of several cardiovascular (CV) diseases. However, in many clinical settings, like chronic kidney disease (CKD), the predictive value of these biomarkers has been questioned. In fact, it is now well established that renal function significantly affects the plasmatic levels of NP and that renal failure is the clinical condition associated with the highest plasmatic levels of these peptides. The complexity of the relation between NP plasmatic levels and CV and renal functions has obvious consequences, as it may limit the predictive value of NP in CV assessment of CKD patients and be a demanding exercise for clinicians involved in the daily management of these patients. This review describes the role of NP in the regulatory response to renal function loss and addresses the main factors involved in the clinical valorization of the peptides in the context of significant renal failure. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.

A Portable Platform for Evaluation of Visual Performance in Glaucoma Patients

PubMed Central

Rosen, Peter N.; Boer, Erwin R.; Gracitelli, Carolina P. B.; Abe, Ricardo Y.; Diniz-Filho, Alberto; Marvasti, Amir H.; Medeiros, Felipe A.

2015-01-01

Purpose To propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes. Design Cross-sectional study. Methods The study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively. Results When adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls. Conclusion A portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls. PMID:26445501

A local circuit model of learned striatal and dopamine cell responses under probabilistic schedules of reward.

PubMed

Tan, Can Ozan; Bullock, Daniel

2008-10-01

Recently, dopamine (DA) neurons of the substantia nigra pars compacta (SNc) were found to exhibit sustained responses related to reward uncertainty, in addition to the phasic responses related to reward-prediction errors (RPEs). Thus, cue-dependent anticipations of the timing, magnitude, and uncertainty of rewards are learned and reflected in components of DA signals. Here we simulate a local circuit model to show how learned uncertainty responses are generated, along with phasic RPE responses, on single trials. Both types of simulated DA responses exhibit the empirically observed dependencies on conditional probability, expected value of reward, and time since onset of the reward-predicting cue. The model's three major pathways compute expected values of cues, timed predictions of reward magnitudes, and uncertainties associated with these predictions. The first two pathways' computations refine those modeled by Brown et al. (1999). The third, newly modeled, pathway involves medium spiny projection neurons (MSPNs) of the striatal matrix, whose axons corelease GABA and substance P, both at synapses with GABAergic neurons in the substantia nigra pars reticulata (SNr) and with distal dendrites (in SNr) of DA neurons whose somas are located in ventral SNc. Corelease enables efficient computation of uncertainty responses that are a nonmonotonic function of the conditional probability of reward, and variability in striatal cholinergic transmission can explain observed individual differences in the amplitudes of uncertainty responses. The involvement of matricial MSPNs and cholinergic transmission within the striatum implies a relation between uncertainty in cue-reward contingencies and action-selection functions of the basal ganglia.

Executive function skills and academic achievement gains in prekindergarten: Contributions of learning-related behaviors.

PubMed

Nesbitt, Kimberly Turner; Farran, Dale Clark; Fuhs, Mary Wagner

2015-07-01

Although research suggests associations between children's executive function skills and their academic achievement, the specific mechanisms that may help explain these associations in early childhood are unclear. This study examined whether children's (N = 1,103; M age = 54.5 months) executive function skills at the beginning of prekindergarten (pre-K) predict their learning-related behaviors in the classroom and whether these behaviors then mediate associations between children's executive function skills and their pre-K literacy, language, and mathematic gains. Learning-related behaviors were quantified in terms of (a) higher levels of involvement in learning opportunities; (b) greater frequency of participation in activities that require sequential steps; (c) more participation in social-learning interactions; and (d) less instances of being unoccupied, disruptive, or in time out. Results indicated that children's learning-related behaviors mediated associations between executive function skills and literacy and mathematics gains through children's level of involvement, sequential learning behaviors, and disengagement from the classroom. The implications of the findings for early childhood education are discussed. (c) 2015 APA, all rights reserved).

Hypothesis: NDL proteins function in stress responses by regulating microtubule organization

PubMed Central

Khatri, Nisha; Mudgil, Yashwanti

2015-01-01

N-MYC DOWNREGULATED-LIKE proteins (NDL), members of the alpha/beta hydrolase superfamily were recently rediscovered as interactors of G-protein signaling in Arabidopsis thaliana. Although the precise molecular function of NDL proteins is still elusive, in animals these proteins play protective role in hypoxia and expression is induced by hypoxia and nickel, indicating role in stress. Homology of NDL1 with animal counterpart N-MYC DOWNREGULATED GENE (NDRG) suggests similar functions in animals and plants. It is well established that stress responses leads to the microtubule depolymerization and reorganization which is crucial for stress tolerance. NDRG is a microtubule-associated protein which mediates the microtubule organization in animals by causing acetylation and increases the stability of α-tubulin. As NDL1 is highly homologous to NDRG, involvement of NDL1 in the microtubule organization during plant stress can also be expected. Discovery of interaction of NDL with protein kinesin light chain- related 1, enodomembrane family protein 70, syntaxin-23, tubulin alpha-2 chain, as a part of G protein interactome initiative encourages us to postulate microtubule stabilizing functions for NDL family in plants. Our search for NDL interactors in G protein interactome also predicts the role of NDL proteins in abiotic stress tolerance management. Based on published report in animals and predicted interacting partners for NDL in G protein interactome lead us to hypothesize involvement of NDL in the microtubule organization during abiotic stress management in plants. PMID:26583023

Hypothesis: NDL proteins function in stress responses by regulating microtubule organization.

PubMed

Khatri, Nisha; Mudgil, Yashwanti

2015-01-01

N-MYC DOWNREGULATED-LIKE proteins (NDL), members of the alpha/beta hydrolase superfamily were recently rediscovered as interactors of G-protein signaling in Arabidopsis thaliana. Although the precise molecular function of NDL proteins is still elusive, in animals these proteins play protective role in hypoxia and expression is induced by hypoxia and nickel, indicating role in stress. Homology of NDL1 with animal counterpart N-MYC DOWNREGULATED GENE (NDRG) suggests similar functions in animals and plants. It is well established that stress responses leads to the microtubule depolymerization and reorganization which is crucial for stress tolerance. NDRG is a microtubule-associated protein which mediates the microtubule organization in animals by causing acetylation and increases the stability of α-tubulin. As NDL1 is highly homologous to NDRG, involvement of NDL1 in the microtubule organization during plant stress can also be expected. Discovery of interaction of NDL with protein kinesin light chain- related 1, enodomembrane family protein 70, syntaxin-23, tubulin alpha-2 chain, as a part of G protein interactome initiative encourages us to postulate microtubule stabilizing functions for NDL family in plants. Our search for NDL interactors in G protein interactome also predicts the role of NDL proteins in abiotic stress tolerance management. Based on published report in animals and predicted interacting partners for NDL in G protein interactome lead us to hypothesize involvement of NDL in the microtubule organization during abiotic stress management in plants.

Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor

PubMed Central

Gillard, Nathalie; Goffinont, Stephane; Buré, Corinne; Davidkova, Marie; Maurizot, Jean-Claude; Cadene, Martine; Spotheim-Maurizot, Melanie

2007-01-01

Understanding the cellular effects of radiation-induced oxidation requires the unravelling of key molecular events, particularly damage to proteins with important cellular functions. The Escherichia coli lactose operon is a classical model of gene regulation systems. Its functional mechanism involves the specific binding of a protein, the repressor, to a specific DNA sequence, the operator. We have shown previously that upon irradiation with γ-rays in solution, the repressor loses its ability to bind the operator. Water radiolysis generates hydroxyl radicals (OH· radicals) which attack the protein. Damage of the repressor DNA-binding domain, called the headpiece, is most likely to be responsible of this loss of function. Using CD, fluorescence spectroscopy and a combination of proteolytic cleavage with MS, we have examined the state of the irradiated headpiece. CD measurements revealed a dose-dependent conformational change involving metastable intermediate states. Fluorescence measurements showed a gradual degradation of tyrosine residues. MS was used to count the number of oxidations in different regions of the headpiece and to narrow down the parts of the sequence bearing oxidized residues. By calculating the relative probabilities of reaction of each amino acid with OH· radicals, we can predict the most probable oxidation targets. By comparing the experimental results with the predictions we conclude that Tyr7, Tyr12, Tyr17, Met42 and Tyr47 are the most likely hotspots of oxidation. The loss of repressor function is thus correlated with chemical modifications and conformational changes of the headpiece. PMID:17263689

Predictive Coding or Evidence Accumulation? False Inference and Neuronal Fluctuations

PubMed Central

Friston, Karl J.; Kleinschmidt, Andreas

2010-01-01

Perceptual decisions can be made when sensory input affords an inference about what generated that input. Here, we report findings from two independent perceptual experiments conducted during functional magnetic resonance imaging (fMRI) with a sparse event-related design. The first experiment, in the visual modality, involved forced-choice discrimination of coherence in random dot kinematograms that contained either subliminal or periliminal motion coherence. The second experiment, in the auditory domain, involved free response detection of (non-semantic) near-threshold acoustic stimuli. We analysed fluctuations in ongoing neural activity, as indexed by fMRI, and found that neuronal activity in sensory areas (extrastriate visual and early auditory cortex) biases perceptual decisions towards correct inference and not towards a specific percept. Hits (detection of near-threshold stimuli) were preceded by significantly higher activity than both misses of identical stimuli or false alarms, in which percepts arise in the absence of appropriate sensory input. In accord with predictive coding models and the free-energy principle, this observation suggests that cortical activity in sensory brain areas reflects the precision of prediction errors and not just the sensory evidence or prediction errors per se. PMID:20369004

Comparison of semantic and episodic memory BOLD fMRI activation in predicting cognitive decline in older adults.

PubMed

Hantke, Nathan; Nielson, Kristy A; Woodard, John L; Breting, Leslie M Guidotti; Butts, Alissa; Seidenberg, Michael; Carson Smith, J; Durgerian, Sally; Lancaster, Melissa; Matthews, Monica; Sugarman, Michael A; Rao, Stephen M

2013-01-01

Previous studies suggest that task-activated functional magnetic resonance imaging (fMRI) can predict future cognitive decline among healthy older adults. The present fMRI study examined the relative sensitivity of semantic memory (SM) versus episodic memory (EM) activation tasks for predicting cognitive decline. Seventy-eight cognitively intact elders underwent neuropsychological testing at entry and after an 18-month interval, with participants classified as cognitively "Stable" or "Declining" based on ≥ 1.0 SD decline in performance. Baseline fMRI scanning involved SM (famous name discrimination) and EM (name recognition) tasks. SM and EM fMRI activation, along with Apolipoprotein E (APOE) ε4 status, served as predictors of cognitive outcome using a logistic regression analysis. Twenty-seven (34.6%) participants were classified as Declining and 51 (65.4%) as Stable. APOE ε4 status alone significantly predicted cognitive decline (R(2) = .106; C index = .642). Addition of SM activation significantly improved prediction accuracy (R(2) = .285; C index = .787), whereas the addition of EM did not (R(2) = .212; C index = .711). In combination with APOE status, SM task activation predicts future cognitive decline better than EM activation. These results have implications for use of fMRI in prevention clinical trials involving the identification of persons at-risk for age-associated memory loss and Alzheimer's disease.

Predicting network modules of cell cycle regulators using relative protein abundance statistics.

PubMed

Oguz, Cihan; Watson, Layne T; Baumann, William T; Tyson, John J

2017-02-28

Parameter estimation in systems biology is typically done by enforcing experimental observations through an objective function as the parameter space of a model is explored by numerical simulations. Past studies have shown that one usually finds a set of "feasible" parameter vectors that fit the available experimental data equally well, and that these alternative vectors can make different predictions under novel experimental conditions. In this study, we characterize the feasible region of a complex model of the budding yeast cell cycle under a large set of discrete experimental constraints in order to test whether the statistical features of relative protein abundance predictions are influenced by the topology of the cell cycle regulatory network. Using differential evolution, we generate an ensemble of feasible parameter vectors that reproduce the phenotypes (viable or inviable) of wild-type yeast cells and 110 mutant strains. We use this ensemble to predict the phenotypes of 129 mutant strains for which experimental data is not available. We identify 86 novel mutants that are predicted to be viable and then rank the cell cycle proteins in terms of their contributions to cumulative variability of relative protein abundance predictions. Proteins involved in "regulation of cell size" and "regulation of G1/S transition" contribute most to predictive variability, whereas proteins involved in "positive regulation of transcription involved in exit from mitosis," "mitotic spindle assembly checkpoint" and "negative regulation of cyclin-dependent protein kinase by cyclin degradation" contribute the least. These results suggest that the statistics of these predictions may be generating patterns specific to individual network modules (START, S/G2/M, and EXIT). To test this hypothesis, we develop random forest models for predicting the network modules of cell cycle regulators using relative abundance statistics as model inputs. Predictive performance is assessed by the areas under receiver operating characteristics curves (AUC). Our models generate an AUC range of 0.83-0.87 as opposed to randomized models with AUC values around 0.50. By using differential evolution and random forest modeling, we show that the model prediction statistics generate distinct network module-specific patterns within the cell cycle network.

Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

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

Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.

2004-08-06

The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene, and assayedmore » embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Measuring conservation of sequence features closely linked to function--such as binding-site clustering--makes better use of comparative sequence data than commonly used methods that examine only sequence identity.« less

The relationship between neuropsychological tests of visuospatial function and lobar cortical thickness.

PubMed

Zink, Davor N; Miller, Justin B; Caldwell, Jessica Z K; Bird, Christopher; Banks, Sarah J

2018-06-01

Tests of visuospatial function are often administered in comprehensive neuropsychological evaluations. These tests are generally considered assays of parietal lobe function; however, the neural correlates of these tests, using modern imaging techniques, are not well understood. In the current study we investigated the relationship between three commonly used tests of visuospatial function and lobar cortical thickness in each hemisphere. Data from 374 patients who underwent a neuropsychological evaluation and MRI scans in an outpatient dementia clinic were included in the analysis. We examined the relationships between cortical thickness, as assessed with Freesurfer, and performance on three tests: Judgment of Line Orientation (JoLO), Block Design (BD) from the Fourth edition of the Wechsler Adult Intelligence Scale, and Brief Visuospatial Memory Test-Revised Copy Trial (BVMT-R-C) in patients who showed overall average performance on these tasks. Using a series of multiple regression models, we assessed which lobe's overall cortical thickness best predicted test performance. Among the individual lobes, JoLO performance was best predicted by cortical thickness in the right temporal lobe. BD performance was best predicted by cortical thickness in the right parietal lobe, and BVMT-R-C performance was best predicted by cortical thickness in the left parietal lobe. Performance on constructional tests of visuospatial function appears to correspond best with underlying cortical thickness of the parietal lobes, while performance on visuospatial judgment tests appears to correspond best to temporal lobe thickness. Future research using voxel-wise and connectivity techniques and including more diverse samples will help further understanding of the regions and networks involved in visuospatial tests.

Prediction of Protein Configurational Entropy (Popcoen).

PubMed

Goethe, Martin; Gleixner, Jan; Fita, Ignacio; Rubi, J Miguel

2018-03-13

A knowledge-based method for configurational entropy prediction of proteins is presented; this methodology is extremely fast, compared to previous approaches, because it does not involve any type of configurational sampling. Instead, the configurational entropy of a query fold is estimated by evaluating an artificial neural network, which was trained on molecular-dynamics simulations of ∼1000 proteins. The predicted entropy can be incorporated into a large class of protein software based on cost-function minimization/evaluation, in which configurational entropy is currently neglected for performance reasons. Software of this type is used for all major protein tasks such as structure predictions, proteins design, NMR and X-ray refinement, docking, and mutation effect predictions. Integrating the predicted entropy can yield a significant accuracy increase as we show exemplarily for native-state identification with the prominent protein software FoldX. The method has been termed Popcoen for Prediction of Protein Configurational Entropy. An implementation is freely available at http://fmc.ub.edu/popcoen/ .

Math and numeracy in young adults with spina bifida and hydrocephalus.

PubMed

Dennis, Maureen; Barnes, Marcia

2002-01-01

The developmental stability of poor math skill was studied in 31 young adults with spina bifida and hydrocephalus (SBH), a neurodevelopmental disorder involving malformations of the brain and spinal cord. Longitudinally, individuals with poor math problem solving as children grew into adults with poor problem solving and limited functional numeracy. As a group, young adults with SBH had poor computation accuracy, computation speed, problem solving, a ndfunctional numeracy. Computation accuracy was related to a supporting cognitive system (working memory for numbers), and functional numeracy was related to one medical history variable (number of lifetime shunt revisions). Adult functional numeracy, but not functional literacy, was predictive of higher levels of social, personal, and community independence.

Origin and Functional Prediction of Pollen Allergens in Plants1[OPEN

PubMed Central

Chen, Miaolin; Xu, Jie; Ren, Kang; Searle, Iain

2016-01-01

Pollen allergies have long been a major pandemic health problem for human. However, the evolutionary events and biological function of pollen allergens in plants remain largely unknown. Here, we report the genome-wide prediction of pollen allergens and their biological function in the dicotyledonous model plant Arabidopsis (Arabidopsis thaliana) and the monocotyledonous model plant rice (Oryza sativa). In total, 145 and 107 pollen allergens were predicted from rice and Arabidopsis, respectively. These pollen allergens are putatively involved in stress responses and metabolic processes such as cell wall metabolism during pollen development. Interestingly, these putative pollen allergen genes were derived from large gene families and became diversified during evolution. Sequence analysis across 25 plant species from green alga to angiosperms suggest that about 40% of putative pollen allergenic proteins existed in both lower and higher plants, while other allergens emerged during evolution. Although a high proportion of gene duplication has been observed among allergen-coding genes, our data show that these genes might have undergone purifying selection during evolution. We also observed that epitopes of an allergen might have a biological function, as revealed by comprehensive analysis of two known allergens, expansin and profilin. This implies a crucial role of conserved amino acid residues in both in planta biological function and allergenicity. Finally, a model explaining how pollen allergens were generated and maintained in plants is proposed. Prediction and systematic analysis of pollen allergens in model plants suggest that pollen allergens were evolved by gene duplication and then functional specification. This study provides insight into the phylogenetic and evolutionary scenario of pollen allergens that will be helpful to future characterization and epitope screening of pollen allergens. PMID:27436829

Origin and Functional Prediction of Pollen Allergens in Plants.

PubMed

Chen, Miaolin; Xu, Jie; Devis, Deborah; Shi, Jianxin; Ren, Kang; Searle, Iain; Zhang, Dabing

2016-09-01

Pollen allergies have long been a major pandemic health problem for human. However, the evolutionary events and biological function of pollen allergens in plants remain largely unknown. Here, we report the genome-wide prediction of pollen allergens and their biological function in the dicotyledonous model plant Arabidopsis (Arabidopsis thaliana) and the monocotyledonous model plant rice (Oryza sativa). In total, 145 and 107 pollen allergens were predicted from rice and Arabidopsis, respectively. These pollen allergens are putatively involved in stress responses and metabolic processes such as cell wall metabolism during pollen development. Interestingly, these putative pollen allergen genes were derived from large gene families and became diversified during evolution. Sequence analysis across 25 plant species from green alga to angiosperms suggest that about 40% of putative pollen allergenic proteins existed in both lower and higher plants, while other allergens emerged during evolution. Although a high proportion of gene duplication has been observed among allergen-coding genes, our data show that these genes might have undergone purifying selection during evolution. We also observed that epitopes of an allergen might have a biological function, as revealed by comprehensive analysis of two known allergens, expansin and profilin. This implies a crucial role of conserved amino acid residues in both in planta biological function and allergenicity. Finally, a model explaining how pollen allergens were generated and maintained in plants is proposed. Prediction and systematic analysis of pollen allergens in model plants suggest that pollen allergens were evolved by gene duplication and then functional specification. This study provides insight into the phylogenetic and evolutionary scenario of pollen allergens that will be helpful to future characterization and epitope screening of pollen allergens. © 2016 American Society of Plant Biologists. All rights reserved.

Flexible Use of Predictive Cues beyond the Orbitofrontal Cortex: Role of the Submedius Thalamic Nucleus.

PubMed

Alcaraz, Fabien; Marchand, Alain R; Vidal, Elisa; Guillou, Alexandre; Faugère, Angélique; Coutureau, Etienne; Wolff, Mathieu

2015-09-23

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions. Significance statement: In the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning. Copyright © 2015 the authors 0270-6474/15/3513183-11$15.00/0.

Capture, Learning, and Classification of Upper Extremity Movement Primitives in Healthy Controls and Stroke Patients

PubMed Central

Guerra, Jorge; Uddin, Jasim; Nilsen, Dawn; Mclnerney, James; Fadoo, Ammarah; Omofuma, Isirame B.; Hughes, Shatif; Agrawal, Sunil; Allen, Peter; Schambra, Heidi M.

2017-01-01

There currently exist no practical tools to identify functional movements in the upper extremities (UEs). This absence has limited the precise therapeutic dosing of patients recovering from stroke. In this proof-of-principle study, we aimed to develop an accurate approach for classifying UE functional movement primitives, which comprise functional movements. Data were generated from inertial measurement units (IMUs) placed on upper body segments of older healthy individuals and chronic stroke patients. Subjects performed activities commonly trained during rehabilitation after stroke. Data processing involved the use of a sliding window to obtain statistical descriptors, and resulting features were processed by a Hidden Markov Model (HMM). The likelihoods of the states, resulting from the HMM, were segmented by a second sliding window and their averages were calculated. The final predictions were mapped to human functional movement primitives using a Logistic Regression algorithm. Algorithm performance was assessed with a leave-one-out analysis, which determined its sensitivity, specificity, and positive and negative predictive values for all classified primitives. In healthy control and stroke participants, our approach identified functional movement primitives embedded in training activities with, on average, 80% precision. This approach may support functional movement dosing in stroke rehabilitation. PMID:28813877

Temporal Prediction Errors Affect Short-Term Memory Scanning Response Time.

PubMed

Limongi, Roberto; Silva, Angélica M

2016-11-01

The Sternberg short-term memory scanning task has been used to unveil cognitive operations involved in time perception. Participants produce time intervals during the task, and the researcher explores how task performance affects interval production - where time estimation error is the dependent variable of interest. The perspective of predictive behavior regards time estimation error as a temporal prediction error (PE), an independent variable that controls cognition, behavior, and learning. Based on this perspective, we investigated whether temporal PEs affect short-term memory scanning. Participants performed temporal predictions while they maintained information in memory. Model inference revealed that PEs affected memory scanning response time independently of the memory-set size effect. We discuss the results within the context of formal and mechanistic models of short-term memory scanning and predictive coding, a Bayes-based theory of brain function. We state the hypothesis that our finding could be associated with weak frontostriatal connections and weak striatal activity.

Ab initio NMR Confirmed Evolutionary Structure Prediction for Organic Molecular Crystals

NASA Astrophysics Data System (ADS)

Pham, Cong-Huy; Kucukbenli, Emine; de Gironcoli, Stefano

2015-03-01

Ab initio crystal structure prediction of even small organic compounds is extremely challenging due to polymorphism, molecular flexibility and difficulties in addressing the dispersion interaction from first principles. We recently implemented vdW-aware density functionals and demonstrated their success in energy ordering of aminoacid crystals. In this work we combine this development with the evolutionary structure prediction method to study cholesterol polymorphs. Cholesterol crystals have paramount importance in various diseases, from cancer to atherosclerosis. The structure of some polymorphs (e.g. ChM, ChAl, ChAh) have already been resolved while some others, which display distinct NMR spectra and are involved in disease formation, are yet to be determined. Here we thoroughly assess the applicability of evolutionary structure prediction to address such real world problems. We validate the newly predicted structures with ab initio NMR chemical shift data using secondary referencing for an improved comparison with experiments.

GENIUS: web server to predict local gene networks and key genes for biological functions.

PubMed

Puelma, Tomas; Araus, Viviana; Canales, Javier; Vidal, Elena A; Cabello, Juan M; Soto, Alvaro; Gutiérrez, Rodrigo A

2017-03-01

GENIUS is a user-friendly web server that uses a novel machine learning algorithm to infer functional gene networks focused on specific genes and experimental conditions that are relevant to biological functions of interest. These functions may have different levels of complexity, from specific biological processes to complex traits that involve several interacting processes. GENIUS also enriches the network with new genes related to the biological function of interest, with accuracies comparable to highly discriminative Support Vector Machine methods. GENIUS currently supports eight model organisms and is freely available for public use at http://networks.bio.puc.cl/genius . genius.psbl@gmail.com. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Predicting functional divergence in protein evolution by site-specific rate shifts

NASA Technical Reports Server (NTRS)

Gaucher, Eric A.; Gu, Xun; Miyamoto, Michael M.; Benner, Steven A.

2002-01-01

Most modern tools that analyze protein evolution allow individual sites to mutate at constant rates over the history of the protein family. However, Walter Fitch observed in the 1970s that, if a protein changes its function, the mutability of individual sites might also change. This observation is captured in the "non-homogeneous gamma model", which extracts functional information from gene families by examining the different rates at which individual sites evolve. This model has recently been coupled with structural and molecular biology to identify sites that are likely to be involved in changing function within the gene family. Applying this to multiple gene families highlights the widespread divergence of functional behavior among proteins to generate paralogs and orthologs.

Functional Overlap between Regions Involved in Speech Perception and in Monitoring One's Own Voice during Speech Production

ERIC Educational Resources Information Center

Zheng, Zane Z.; Munhall, Kevin G.; Johnsrude, Ingrid S.

2010-01-01

The fluency and the reliability of speech production suggest a mechanism that links motor commands and sensory feedback. Here, we examined the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or…

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions.

PubMed

Zhou, Hufeng; Gao, Shangzhi; Nguyen, Nam Ninh; Fan, Mengyuan; Jin, Jingjing; Liu, Bing; Zhao, Liang; Xiong, Geng; Tan, Min; Li, Shijun; Wong, Limsoon

2014-04-08

H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies.

Using Spatial Multiple Regression to Identify Intrinsic Connectivity Networks Involved in Working Memory Performance

PubMed Central

Gordon, Evan M.; Stollstorff, Melanie; Vaidya, Chandan J.

2012-01-01

Many researchers have noted that the functional architecture of the human brain is relatively invariant during task performance and the resting state. Indeed, intrinsic connectivity networks (ICNs) revealed by resting-state functional connectivity analyses are spatially similar to regions activated during cognitive tasks. This suggests that patterns of task-related activation in individual subjects may result from the engagement of one or more of these ICNs; however, this has not been tested. We used a novel analysis, spatial multiple regression, to test whether the patterns of activation during an N-back working memory task could be well described by a linear combination of ICNs delineated using Independent Components Analysis at rest. We found that across subjects, the cingulo-opercular Set Maintenance ICN, as well as right and left Frontoparietal Control ICNs, were reliably activated during working memory, while Default Mode and Visual ICNs were reliably deactivated. Further, involvement of Set Maintenance, Frontoparietal Control, and Dorsal Attention ICNs was sensitive to varying working memory load. Finally, the degree of left Frontoparietal Control network activation predicted response speed, while activation in both left Frontoparietal Control and Dorsal Attention networks predicted task accuracy. These results suggest that a close relationship between resting-state networks and task-evoked activation is functionally relevant for behavior, and that spatial multiple regression analysis is a suitable method for revealing that relationship. PMID:21761505

Evolution and Cellular Function of Monothiol Glutaredoxins: Involvement in Iron-Sulphur Cluster Assembly

PubMed Central

Vilella, Felipe; Alves, Rui; Rodríguez-Manzaneque, María Teresa; Bellí, Gemma; Swaminathan, Swarna; Sunnerhagen, Per

2004-01-01

A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron–sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron–sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary co-occurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell. PMID:18629168

Risks for Early Substance Involvement Associated with Parental Alcoholism and Parental Separation in an Adolescent Female Cohort*

PubMed Central

Waldron, Mary; Vaughan, Ellen L.; Bucholz, Kathleen K.; Lynskey, Michael T.; Sartor, Carolyn E.; Duncan, Alexis E.; Madden, Pamela A.F.; Heath, Andrew C.

2014-01-01

Background We examined timing of substance involvement as a joint function of parental history of alcoholism and parental separation during childhood. Method Data were drawn from a large cohort of female like-sex twins [n = 613 African Ancestry (AA), n = 3550 European or other Ancestry (EA)]. Cox proportional hazards regression was conducted predicting age at first use of alcohol, first alcohol intoxication, first use and regular use of cigarettes, and first use of cannabis and other illicit drugs from dummy variables coding for parental alcoholism and parental separation. Propensity score analysis was also conducted comparing intact and separated families by predicted probability of parental separation. Results In EA families, increased risk of substance involvement was found in both alcoholic and separated families, particularly through ages 10 or 14 years, with risk to offspring from alcoholic separated families further increased. In AA families, associations with parental alcoholism and parental separation were weak and with few exceptions statistically nonsignificant. While propensity score findings confirmed unique risks observed in EA families, intact and separated AA families were poorly matched on risk-factors presumed to predate parental separation, especially parental alcoholism, requiring cautious interpretation of AA survival-analytic findings. Conclusion For offspring of European ancestry, parental separation predicts early substance involvement that is not explained by parental alcoholism nor associated family background characteristics. Additional research is needed to better characterize risks associated with parental separation in African American families. PMID:24647368

Risks for early substance involvement associated with parental alcoholism and parental separation in an adolescent female cohort.

PubMed

Waldron, Mary; Vaughan, Ellen L; Bucholz, Kathleen K; Lynskey, Michael T; Sartor, Carolyn E; Duncan, Alexis E; Madden, Pamela A F; Heath, Andrew C

2014-05-01

We examined timing of substance involvement as a joint function of parental history of alcoholism and parental separation during childhood. Data were drawn from a large cohort of female like-sex twins [n=613 African Ancestry (AA), n=3550 European or other ancestry (EA)]. Cox proportional hazards regression was conducted predicting age at first use of alcohol, first alcohol intoxication, first use and regular use of cigarettes, and first use of cannabis and other illicit drugs from dummy variables coding for parental alcoholism and parental separation. Propensity score analysis was also conducted comparing intact and separated families by predicted probability of parental separation. In EA families, increased risk of substance involvement was found in both alcoholic and separated families, particularly through ages 10 or 14 years, with risk to offspring from alcoholic separated families further increased. In AA families, associations with parental alcoholism and parental separation were weak and with few exceptions statistically nonsignificant. While propensity score findings confirmed unique risks observed in EA families, intact and separated AA families were poorly matched on risk-factors presumed to predate parental separation, especially parental alcoholism, requiring cautious interpretation of AA survival-analytic findings. For offspring of European ancestry, parental separation predicts early substance involvement that is not explained by parental alcoholism nor associated family background characteristics. Additional research is needed to better characterize risks associated with parental separation in African American families. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The four-loop six-gluon NMHV ratio function

DOE PAGES

Dixon, Lance J.; von Hippel, Matt; McLeod, Andrew J.

2016-01-11

We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N=4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q¯ differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We test the result againstmore » multi-Regge predictions at NNLL and N 3LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. As a result, we also provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.« less

The four-loop six-gluon NMHV ratio function

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

Dixon, Lance J.; von Hippel, Matt; McLeod, Andrew J.

2016-01-11

We use the hexagon function bootstrap to compute the ratio function which characterizes the next-to-maximally-helicity-violating (NMHV) six-point amplitude in planar N = 4 super-Yang-Mills theory at four loops. A powerful constraint comes from dual superconformal invariance, in the form of a Q - differential equation, which heavily constrains the first derivatives of the transcendental functions entering the ratio function. At four loops, it leaves only a 34-parameter space of functions. Constraints from the collinear limits, and from the multi-Regge limit at the leading-logarithmic (LL) and next-to-leading-logarithmic (NLL) order, suffice to fix these parameters and obtain a unique result. We testmore » the result against multi- Regge predictions at NNLL and N 3LL, and against predictions from the operator product expansion involving one and two flux-tube excitations; all cross-checks are satisfied. We also study the analytical and numerical behavior of the parity-even and parity-odd parts on various lines and surfaces traversing the three-dimensional space of cross ratios. As part of this program, we characterize all irreducible hexagon functions through weight eight in terms of their coproduct. Furthermore, we provide representations of the ratio function in particular kinematic regions in terms of multiple polylogarithms.« less

Dehalogenation of aromatics by nucleophilic aromatic substitution.

PubMed

Sadowsky, Daniel; McNeill, Kristopher; Cramer, Christopher J

2014-09-16

Nucleophilic aromatic substitution has been implicated as a mechanism for both the biotic and abiotic hydrodehalogenation of aromatics. Two mechanisms for the aqueous dehalogenation of aromatics involving nucleophilic aromatic substitution with hydride as a nucleophile are investigated using a validated density functional and continuum solvation protocol. For chlorinated and brominated aromatics, nucleophilic addition ortho to carbon-halogen bonds via an anionic intermediate is predicted to be the preferred mechanism in the majority of cases, while concerted substitution is predicted to be preferred for most fluorinated aromatics. Nucleophilic aromatic substitution reactions with the hydroxide and hydrosulfide anions as nucleophiles are also investigated and compared.

Predicting the Impact of Alternative Splicing on Plant MADS Domain Protein Function

PubMed Central

Severing, Edouard I.; van Dijk, Aalt D. J.; Morabito, Giuseppa; Busscher-Lange, Jacqueline; Immink, Richard G. H.; van Ham, Roeland C. H. J.

2012-01-01

Several genome-wide studies demonstrated that alternative splicing (AS) significantly increases the transcriptome complexity in plants. However, the impact of AS on the functional diversity of proteins is difficult to assess using genome-wide approaches. The availability of detailed sequence annotations for specific genes and gene families allows for a more detailed assessment of the potential effect of AS on their function. One example is the plant MADS-domain transcription factor family, members of which interact to form protein complexes that function in transcription regulation. Here, we perform an in silico analysis of the potential impact of AS on the protein-protein interaction capabilities of MIKC-type MADS-domain proteins. We first confirmed the expression of transcript isoforms resulting from predicted AS events. Expressed transcript isoforms were considered functional if they were likely to be translated and if their corresponding AS events either had an effect on predicted dimerisation motifs or occurred in regions known to be involved in multimeric complex formation, or otherwise, if their effect was conserved in different species. Nine out of twelve MIKC MADS-box genes predicted to produce multiple protein isoforms harbored putative functional AS events according to those criteria. AS events with conserved effects were only found at the borders of or within the K-box domain. We illustrate how AS can contribute to the evolution of interaction networks through an example of selective inclusion of a recently evolved interaction motif in the MADS AFFECTING FLOWERING1-3 (MAF1–3) subclade. Furthermore, we demonstrate the potential effect of an AS event in SHORT VEGETATIVE PHASE (SVP), resulting in the deletion of a short sequence stretch including a predicted interaction motif, by overexpression of the fully spliced and the alternatively spliced SVP transcripts. For most of the AS events we were able to formulate hypotheses about the potential impact on the interaction capabilities of the encoded MIKC proteins. PMID:22295091

Association of Salivary Microbiota with Dental Caries Incidence with Dentine Involvement after 4 Years.

PubMed

Kim, Bong-Soo; Han, Dong-Hun; Lee, Ho; Oh, Bumjo

2018-03-28

Salivary microbiota alterations can correlate with dental caries development in children, and mechanisms mediating this association need to be studied in further detail. Our study explored salivary microbiota shifts in children and their association with the incidence of dental caries with dentine involvement. Salivary samples were collected from children with caries and their subsequently matched caries-free controls before and after caries development. The microbiota was analyzed by 16S rRNA gene-based high-throughput sequencing. The salivary microbiota was more diverse in caries-free subjects than in those with dental caries with dentine involvement (DC). Although both groups exhibited similar shifts in microbiota composition, an association with caries was found by function prediction. Analysis of potential microbiome functions revealed that Granulicatella, Streptococcus, Bulleidia , and Staphylococcus in the DC group could be associated with the bacterial invasion of epithelial cells, phosphotransferase system, and D -alanine metabolism, whereas Neisseria, Lautropia , and Leptotrichia in caries-free subjects could be associated with bacterial motility protein genes, linoleic acid metabolism, and flavonoid biosynthesis, suggesting that functional differences in the salivary microbiota may be associated with caries formation. These results expand the current understanding of the functional significance of the salivary microbiome in caries development, and may facilitate the identification of novel biomarkers and treatment targets.

Domain fusion analysis by applying relational algebra to protein sequence and domain databases

PubMed Central

Truong, Kevin; Ikura, Mitsuhiko

2003-01-01

Background Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. Results This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at . Conclusion As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time. PMID:12734020

Should regional ventilation function be considered during radiation treatment planning to prevent radiation-induced complications?

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

Lan, Fujun; Jeudy, Jean; D’Souza, Warren

Purpose: To investigate the incorporation of pretherapy regional ventilation function in predicting radiation fibrosis (RF) in stage III nonsmall cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: Thirty-seven patients with stage III NSCLC were retrospectively studied. Patients received one cycle of cisplatin–gemcitabine, followed by two to three cycles of cisplatin–etoposide concurrently with involved-field thoracic radiotherapy (46–66 Gy; 2 Gy/fraction). Pretherapy regional ventilation images of the lung were derived from 4D computed tomography via a density change–based algorithm with mass correction. In addition to the conventional dose–volume metrics (V{sub 20}, V{sub 30}, V{sub 40}, and mean lung dose),more » dose–function metrics (fV{sub 20}, fV{sub 30}, fV{sub 40}, and functional mean lung dose) were generated by combining regional ventilation and radiation dose. A new class of metrics was derived and referred to as dose–subvolume metrics (sV{sub 20}, sV{sub 30}, sV{sub 40}, and subvolume mean lung dose); these were defined as the conventional dose–volume metrics computed on the functional lung. Area under the receiver operating characteristic curve (AUC) values and logistic regression analyses were used to evaluate these metrics in predicting hallmark characteristics of RF (lung consolidation, volume loss, and airway dilation). Results: AUC values for the dose–volume metrics in predicting lung consolidation, volume loss, and airway dilation were 0.65–0.69, 0.57–0.70, and 0.69–0.76, respectively. The respective ranges for dose–function metrics were 0.63–0.66, 0.61–0.71, and 0.72–0.80 and for dose–subvolume metrics were 0.50–0.65, 0.65–0.75, and 0.73–0.85. Using an AUC value = 0.70 as cutoff value suggested that at least one of each type of metrics (dose–volume, dose–function, dose–subvolume) was predictive for volume loss and airway dilation, whereas lung consolidation cannot be accurately predicted by any of the metrics. Logistic regression analyses showed that dose–function and dose–subvolume metrics were significant (P values ≤ 0.02) in predicting volume airway dilation. Likelihood ratio test showed that when combining dose–function and/or dose–subvolume metrics with dose–volume metrics, the achieved improvements of prediction accuracy on volume loss and airway dilation were significant (P values ≤ 0.04). Conclusions: The authors’ results demonstrated that the inclusion of regional ventilation function improved accuracy in predicting RF. In particular, dose–subvolume metrics provided a promising method for preventing radiation-induced pulmonary complications.« less

A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations | Office of Cancer Genomics

Cancer.gov

Molecular alterations involving the PI3K/Akt/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/Akt/mTOR converged on similar sets of downstream transcriptional targets.

Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology.

PubMed

Schultz, Wolfram

2004-04-01

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The involved brain structures include groups of dopamine neurons, the striatum including the nucleus accumbens, the orbitofrontal cortex and the amygdala. The reward information is fed to brain structures involved in decision-making and organisation of behaviour, such as the dorsolateral prefrontal cortex and possibly the parietal cortex. The neural coding of basic reward terms derived from formal theories puts the neurophysiological investigation of reward mechanisms on firm conceptual grounds and provides neural correlates for the function of rewards in learning, approach behaviour and decision-making.

GARN: Sampling RNA 3D Structure Space with Game Theory and Knowledge-Based Scoring Strategies.

PubMed

Boudard, Mélanie; Bernauer, Julie; Barth, Dominique; Cohen, Johanne; Denise, Alain

2015-01-01

Cellular processes involve large numbers of RNA molecules. The functions of these RNA molecules and their binding to molecular machines are highly dependent on their 3D structures. One of the key challenges in RNA structure prediction and modeling is predicting the spatial arrangement of the various structural elements of RNA. As RNA folding is generally hierarchical, methods involving coarse-grained models hold great promise for this purpose. We present here a novel coarse-grained method for sampling, based on game theory and knowledge-based potentials. This strategy, GARN (Game Algorithm for RNa sampling), is often much faster than previously described techniques and generates large sets of solutions closely resembling the native structure. GARN is thus a suitable starting point for the molecular modeling of large RNAs, particularly those with experimental constraints. GARN is available from: http://garn.lri.fr/.

Food Antioxidants: Chemical Insights at the Molecular Level.

PubMed

Galano, Annia; Mazzone, Gloria; Alvarez-Diduk, Ruslán; Marino, Tiziana; Alvarez-Idaboy, J Raúl; Russo, Nino

2016-01-01

In this review, we briefly summarize the reliability of the density functional theory (DFT)-based methods to accurately predict the main antioxidant properties and the reaction mechanisms involved in the free radical-scavenging reactions of chemical compounds present in food. The analyzed properties are the bond dissociation energies, in particular those involving OH bonds, electron transfer enthalpies, adiabatic ionization potentials, and proton affinities. The reaction mechanisms are hydrogen-atom transfer, proton-coupled electron transfer, radical adduct formation, single electron transfer, sequential electron proton transfer, proton-loss electron transfer, and proton-loss hydrogen-atom transfer. Furthermore, the chelating ability of these compounds and its role in decreasing or inhibiting the oxidative stress induced by Fe(III) and Cu(II) are considered. Comparisons between theoretical and experimental data confirm that modern theoretical tools are not only able to explain controversial experimental facts but also to predict chemical behavior.

Reasons for drinking as predictors of alcohol involvement one year later among HIV-infected individuals with and without hepatitis C.

PubMed

Elliott, Jennifer C; Stohl, Malka; Aharonovich, Efrat; O'Leary, Ann; Hasin, Deborah S

2016-12-01

Heavy drinking can be harmful for individuals with HIV, particularly those coinfected with hepatitis C virus (HCV). HIV patients' reasons for drinking predict short-term alcohol involvement, but whether they predict longer-term involvement is unknown. Also, it remains unknown whether these motives are differentially predictive for HIV monoinfected and HIV/HCV coinfected patients. HIV-infected heavy drinkers (n = 254) participated in a randomized trial of brief alcohol interventions, 236 (92.9%) of whom reported on baseline motives and alcohol involvement 12 months later (77.1% male, 94.9% minority, 30.6% with HCV). Greater endorsement of baseline drinking to cope with negative affect predicted greater alcohol dependence symptoms at 12 months (incident rate ratio [IRR] = 1.80, p < 0.05), while greater endorsement of baseline drinking due to social pressure predicted fewer drinks consumed at 12 months (IRR = 0.67, p < 0.05). Coping and social reasons were both predictive for HIV monoinfected patients, whereas only coping reasons were predictive for HIV/HCV coinfected patients. Drinking for coping and social reasons predict alcohol involvement 12 months later; however, social reasons may only be important for HIV monoinfected patients. Understanding patient reasons for drinking may help predict patient risk up to a year later. KEY MESSAGES Among HIV patients, drinking motives predict alcohol involvement 12 months later. For HIV monoinfected patients, drinking to cope and drinking for social reasons predict 12-month alcohol involvement. For HIV/Hepatitis C coinfected patients, coping (but not social) motives predict 12-month alcohol involvement.

Alternative mechanisms alter the emergent properties of self-organization in mussel beds

PubMed Central

Liu, Quan-Xing; Weerman, Ellen J.; Herman, Peter M. J.; Olff, Han; van de Koppel, Johan

2012-01-01

Theoretical models predict that spatial self-organization can have important, unexpected implications by affecting the functioning of ecosystems in terms of resilience and productivity. Whether and how these emergent effects depend on specific formulations of the underlying mechanisms are questions that are often ignored. Here, we compare two alternative models of regular spatial pattern formation in mussel beds that have different mechanistic descriptions of the facilitative interactions between mussels. The first mechanism involves a reduced mussel loss rate at high density owing to mutual protection between the mussels, which is the basis of prior studies on the pattern formation in mussels. The second mechanism assumes, based on novel experimental evidence, that mussels feed more efficiently on top of mussel-generated hummocks. Model simulations point out that the second mechanism produces very similar types of spatial patterns in mussel beds. Yet the mechanisms predict a strikingly contrasting effect of these spatial patterns on ecosystem functioning, in terms of productivity and resilience. In the first model, where high mussel densities reduce mussel loss rates, patterns are predicted to strongly increase productivity and decrease the recovery time of the bed following a disturbance. When pattern formation is generated by increased feeding efficiency on hummocks, only minor emergent effects of pattern formation on ecosystem functioning are predicted. Our results provide a warning against predictions of the implications and emergent properties of spatial self-organization, when the mechanisms that underlie self-organization are incompletely understood and not based on the experimental study. PMID:22418256

A novel pathway for the biosynthesis of heme in Archaea: genome-based bioinformatic predictions and experimental evidence.

PubMed

Storbeck, Sonja; Rolfes, Sarah; Raux-Deery, Evelyne; Warren, Martin J; Jahn, Dieter; Layer, Gunhild

2010-12-13

Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. In Eukaryota and Bacteria heme is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceeds via an alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in heme d(1) biosynthesis. To initiate an experimental verification of our proposals two Methanosarcina barkeri proteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified.

A Novel Pathway for the Biosynthesis of Heme in Archaea: Genome-Based Bioinformatic Predictions and Experimental Evidence

PubMed Central

Storbeck, Sonja; Rolfes, Sarah; Raux-Deery, Evelyne; Warren, Martin J.; Jahn, Dieter; Layer, Gunhild

2010-01-01

Heme is an essential prosthetic group for many proteins involved in fundamental biological processes in all three domains of life. In Eukaryota and Bacteria heme is formed via a conserved and well-studied biosynthetic pathway. Surprisingly, in Archaea heme biosynthesis proceeds via an alternative route which is poorly understood. In order to formulate a working hypothesis for this novel pathway, we searched 59 completely sequenced archaeal genomes for the presence of gene clusters consisting of established heme biosynthetic genes and colocalized conserved candidate genes. Within the majority of archaeal genomes it was possible to identify such heme biosynthesis gene clusters. From this analysis we have been able to identify several novel heme biosynthesis genes that are restricted to archaea. Intriguingly, several of the encoded proteins display similarity to enzymes involved in heme d 1 biosynthesis. To initiate an experimental verification of our proposals two Methanosarcina barkeri proteins predicted to catalyze the initial steps of archaeal heme biosynthesis were recombinantly produced, purified, and their predicted enzymatic functions verified. PMID:21197080

Airframe Noise Prediction by Acoustic Analogy: Revisited

NASA Technical Reports Server (NTRS)

Farassat, F.; Casper, Jay H.; Tinetti, A.; Dunn, M. H.

2006-01-01

The present work follows a recent survey of airframe noise prediction methodologies. In that survey, Lighthill s acoustic analogy was identified as the most prominent analytical basis for current approaches to airframe noise research. Within this approach, a problem is typically modeled with the Ffowcs Williams and Hawkings (FW-H) equation, for which a geometry-independent solution is obtained by means of the use of the free-space Green function (FSGF). Nonetheless, the aeroacoustic literature would suggest some interest in the use of tailored or exact Green s function (EGF) for aerodynamic noise problems involving solid boundaries, in particular, for trailing edge (TE) noise. A study of possible applications of EGF for prediction of broadband noise from turbulent flow over an airfoil surface and the TE is, therefore, the primary topic of the present work. Typically, the applications of EGF in the literature have been limited to TE noise prediction at low Mach numbers assuming that the normal derivative of the pressure vanishes on the airfoil surface. To extend the application of EGF to higher Mach numbers, the uniqueness of the solution of the wave equation when either the Dirichlet or the Neumann boundary condition (BC) is specified on a deformable surface in motion. The solution of Lighthill s equation with either the Dirichlet or the Neumann BC is given for such a surface using EGFs. These solutions involve both surface and volume integrals just like the solution of FW-H equation using FSGF. Insight drawn from this analysis is evoked to discuss the potential application of EGF to broadband noise prediction. It appears that the use of a EGF offers distinct advantages for predicting TE noise of an airfoil when the normal pressure gradient vanishes on the airfoil surface. It is argued that such an approach may also apply to an airfoil in motion. However, for the prediction of broadband noise not directly associated with a trailing edge, the use of EGF does not appear to offer any advantages over the use of FSGF at the present stage of development. It is suggested here that the applications of EGF for airframe noise analysis be continued. As an example pertinent to airframe noise prediction, the Fast Scattering Code of NASA Langley is utilized to obtain the EGF numerically on the surface of a three dimensional wing with a flap and leading edge slat in uniform rectilinear motion. The interpretation and use of these numerical Green functions are then discussed.

A k-omega multivariate beta PDF for supersonic turbulent combustion

NASA Technical Reports Server (NTRS)

Alexopoulos, G. A.; Baurle, R. A.; Hassan, H. A.

1993-01-01

In a recent attempt by the authors at predicting measurements in coaxial supersonic turbulent reacting mixing layers involving H2 and air, a number of discrepancies involving the concentrations and their variances were noted. The turbulence model employed was a one-equation model based on the turbulent kinetic energy. This required the specification of a length scale. In an attempt at detecting the cause of the discrepancy, a coupled k-omega joint probability density function (PDF) is employed in conjunction with a Navier-Stokes solver. The results show that improvements resulting from a k-omega model are quite modest.

Decreased Functional Brain Connectivity in Adolescents with Internet Addiction

PubMed Central

Hong, Soon-Beom; Zalesky, Andrew; Cocchi, Luca; Fornito, Alex; Choi, Eun-Jung; Kim, Ho-Hyun; Suh, Jeong-Eun; Kim, Chang-Dai; Kim, Jae-Won; Yi, Soon-Hyung

2013-01-01

Background Internet addiction has become increasingly recognized as a mental disorder, though its neurobiological basis is unknown. This study used functional neuroimaging to investigate whole-brain functional connectivity in adolescents diagnosed with internet addiction. Based on neurobiological changes seen in other addiction related disorders, it was predicted that connectivity disruptions in adolescents with internet addiction would be most prominent in cortico-striatal circuitry. Methods Participants were 12 adolescents diagnosed with internet addiction and 11 healthy comparison subjects. Resting-state functional magnetic resonance images were acquired, and group differences in brain functional connectivity were analyzed using the network-based statistic. We also analyzed network topology, testing for between-group differences in key graph-based network measures. Results Adolescents with internet addiction showed reduced functional connectivity spanning a distributed network. The majority of impaired connections involved cortico-subcortical circuits (∼24% with prefrontal and ∼27% with parietal cortex). Bilateral putamen was the most extensively involved subcortical brain region. No between-group difference was observed in network topological measures, including the clustering coefficient, characteristic path length, or the small-worldness ratio. Conclusions Internet addiction is associated with a widespread and significant decrease of functional connectivity in cortico-striatal circuits, in the absence of global changes in brain functional network topology. PMID:23451272

Right Lateral Cerebellum Represents Linguistic Predictability.

PubMed

Lesage, Elise; Hansen, Peter C; Miall, R Chris

2017-06-28

Mounting evidence indicates that posterolateral portions of the cerebellum (right Crus I/II) contribute to language processing, but the nature of this role remains unclear. Based on a well-supported theory of cerebellar motor function, which ascribes to the cerebellum a role in short-term prediction through internal modeling, we hypothesize that right cerebellar Crus I/II supports prediction of upcoming sentence content. We tested this hypothesis using event-related fMRI in male and female human subjects by manipulating the predictability of written sentences. Our design controlled for motor planning and execution, as well as for linguistic features and working memory load; it also allowed separation of the prediction interval from the presentation of the final sentence item. In addition, three further fMRI tasks captured semantic, phonological, and orthographic processing to shed light on the nature of the information processed. As hypothesized, activity in right posterolateral cerebellum correlated with the predictability of the upcoming target word. This cerebellar region also responded to prediction error during the outcome of the trial. Further, this region was engaged in phonological, but not semantic or orthographic, processing. This is the first imaging study to demonstrate a right cerebellar contribution in language comprehension independently from motor, cognitive, and linguistic confounds. These results complement our work using other methodologies showing cerebellar engagement in linguistic prediction and suggest that internal modeling of phonological representations aids language production and comprehension. SIGNIFICANCE STATEMENT The cerebellum is traditionally seen as a motor structure that allows for smooth movement by predicting upcoming signals. However, the cerebellum is also consistently implicated in nonmotor functions such as language and working memory. Using fMRI, we identify a cerebellar area that is active when words are predicted and when these predictions are violated. This area is active in a separate task that requires phonological processing, but not in tasks that require semantic or visuospatial processing. Our results support the idea of prediction as a unifying cerebellar function in motor and nonmotor domains. We provide new insights by linking the cerebellar role in prediction to its role in verbal working memory, suggesting that these predictions involve phonological processing. Copyright © 2017 Lesage et al.

Stoichiometry of Nck-dependent actin polymerization in living cells

PubMed Central

Ditlev, Jonathon A.; Michalski, Paul J.; Huber, Greg; Rivera, Gonzalo M.; Mohler, William A.

2012-01-01

Regulation of actin dynamics through the Nck/N-WASp (neural Wiskott–Aldrich syndrome protein)/Arp2/3 pathway is essential for organogenesis, cell invasiveness, and pathogen infection. Although many of the proteins involved in this pathway are known, the detailed mechanism by which it functions remains undetermined. To examine the signaling mechanism, we used a two-pronged strategy involving computational modeling and quantitative experimentation. We developed predictions for Nck-dependent actin polymerization using the Virtual Cell software system. In addition, we used antibody-induced aggregation of membrane-targeted Nck SH3 domains to test these predictions and to determine how the number of molecules in Nck aggregates and the density of aggregates affected localized actin polymerization in living cells. Our results indicate that the density of Nck molecules in aggregates is a critical determinant of actin polymerization. Furthermore, results from both computational simulations and experimentation support a model in which the Nck/N-WASp/Arp2/3 stoichiometry is 4:2:1. These results provide new insight into activities involving localized actin polymerization, including tumor cell invasion, microbial pathogenesis, and T cell activation. PMID:22613834

Relating spatial perspective taking to the perception of other's affordances: providing a foundation for predicting the future behavior of others

PubMed Central

Creem-Regehr, Sarah H.; Gagnon, Kyle T.; Geuss, Michael N.; Stefanucci, Jeanine K.

2013-01-01

Understanding what another agent can see relates functionally to the understanding of what they can do. We propose that spatial perspective taking and perceiving other's affordances, while two separate spatial processes, together share the common social function of predicting the behavior of others. Perceiving the action capabilities of others allows for a common understanding of how agents may act together. The ability to take another's perspective focuses an understanding of action goals so that more precise understanding of intentions may result. This review presents an analysis of these complementary abilities, both in terms of the frames of reference and the proposed sensorimotor mechanisms involved. Together, we argue for the importance of reconsidering the role of basic spatial processes to explain more complex behaviors. PMID:24068992

Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine.

PubMed

Kumar, Avishek; Butler, Brandon M; Kumar, Sudhir; Ozkan, S Banu

2015-12-01

Sequencing technologies are revealing many new non-synonymous single nucleotide variants (nsSNVs) in each personal exome. To assess their functional impacts, comparative genomics is frequently employed to predict if they are benign or not. However, evolutionary analysis alone is insufficient, because it misdiagnoses many disease-associated nsSNVs, such as those at positions involved in protein interfaces, and because evolutionary predictions do not provide mechanistic insights into functional change or loss. Structural analyses can aid in overcoming both of these problems by incorporating conformational dynamics and allostery in nSNV diagnosis. Finally, protein-protein interaction networks using systems-level methodologies shed light onto disease etiology and pathogenesis. Bridging these network approaches with structurally resolved protein interactions and dynamics will advance genomic medicine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural correlates of social motivation: an fMRI study on power versus affiliation.

PubMed

Quirin, Markus; Meyer, Frank; Heise, Nils; Kuhl, Julius; Küstermann, Ekkehard; Strüber, Daniel; Cacioppo, John T

2013-06-01

Power versus affiliation motivations refer to two different strivings relevant in the context of social relationships. We used functional magnetic resonance imaging (fMRI) to determine neural structures involved in power versus affiliation motivation based on an individual differences approach. Seventeen participants provided self-reports of power and affiliation motives and were presented with love, power-related, and control movie clips. The power motive predicted activity in four clusters within the left prefrontal cortex (PFC), while participants viewed power-related film clips. The affiliation motive predicted activity in the right putamen/pallidum while participants viewed love stories. The present findings extend previous research on social motivations to the level of neural functioning and suggest differential networks for power-related versus affiliation-related social motivations. Copyright © 2012 Elsevier B.V. All rights reserved.

EvoCor: a platform for predicting functionally related genes using phylogenetic and expression profiles.

PubMed

Dittmar, W James; McIver, Lauren; Michalak, Pawel; Garner, Harold R; Valdez, Gregorio

2014-07-01

The wealth of publicly available gene expression and genomic data provides unique opportunities for computational inference to discover groups of genes that function to control specific cellular processes. Such genes are likely to have co-evolved and be expressed in the same tissues and cells. Unfortunately, the expertise and computational resources required to compare tens of genomes and gene expression data sets make this type of analysis difficult for the average end-user. Here, we describe the implementation of a web server that predicts genes involved in affecting specific cellular processes together with a gene of interest. We termed the server 'EvoCor', to denote that it detects functional relationships among genes through evolutionary analysis and gene expression correlation. This web server integrates profiles of sequence divergence derived by a Hidden Markov Model (HMM) and tissue-wide gene expression patterns to determine putative functional linkages between pairs of genes. This server is easy to use and freely available at http://pilot-hmm.vbi.vt.edu/. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Clinical Value of Dorsal Medulla Oblongata Involvement Detected with Conventional MRI for Prediction of Outcome in Children with Enterovirus 71-related Brainstem Encephalitis.

PubMed

Liu, Kun; Zhou, Yongjin; Cui, Shihan; Song, Jiawen; Ye, Peipei; Xiang, Wei; Huang, Xiaoyan; Chen, Yiping; Yan, Zhihan; Ye, Xinjian

2018-04-05

Brainstem encephalitis is the most common neurologic complication after enterovirus 71 infection. The involvement of brainstem, especially the dorsal medulla oblongata, can cause severe sequelae or death in children with enterovirus 71 infection. We aimed to determine the prevalence of dorsal medulla oblongata involvement in children with enterovirus 71-related brainstem encephalitis (EBE) by using conventional MRI and to evaluate the value of dorsal medulla oblongata involvement in outcome prediction. 46 children with EBE were enrolled in the study. All subjects underwent a 1.5 Tesla MR examination of the brain. The disease distribution and clinical data were collected. Dichotomized outcomes (good versus poor) at longer than 6 months were available for 28 patients. Logistic regression was used to determine whether the MRI-confirmed dorsal medulla oblongata involvement resulted in improved clinical outcome prediction when compared with other location involvement. Of the 46 patients, 35 had MRI evidence of dorsal medulla oblongata involvement, 32 had pons involvement, 10 had midbrain involvement, and 7 had dentate nuclei involvement. Patients with dorsal medulla oblongata involvement or multiple area involvement were significantly more often in the poor outcome group than in the good outcome group. Logistic regression analysis showed that dorsal medulla oblongata involvement was the most significant single variable in outcome prediction (predictive accuracy, 90.5%), followed by multiple area involvement, age, and initial glasgow coma scale score. Dorsal medulla oblongata involvement on conventional MRI correlated significantly with poor outcomes in EBE children, improved outcome prediction when compared with other clinical and disease location variables, and was most predictive when combined with multiple area involvement, glasgow coma scale score and age.

Factors involved in making post-performance judgments in mathematics problem-solving.

PubMed

García Fernández, Trinidad; Kroesbergen, Evelyn; Rodríguez Pérez, Celestino; González-Castro, Paloma; González-Pienda, Julio A

2015-01-01

This study examines the impact of executive functions, affective-motivational variables related to mathematics, mathematics achievement and task characteristics on fifth and sixth graders’ calibration accuracy after completing two mathematical problems. A sample of 188 students took part in the study. They were divided into two groups as function of their judgment accuracy after completing the two tasks (accurate= 79, inaccurate= 109). Differences between these groups were examined. The discriminative value of these variables to predict group membership was analyzed, as well as the effect of age, gender, and grade level. The results indicated that accurate students showed better levels of executive functioning, and more positive feelings, beliefs, and motivation related to mathematics. They also spent more time on the tasks. Mathematics achievement, perceived usefulness of mathematics, and time spent on Task 1 significantly predicted group membership, classifying 71.3% of the sample correctly. These results support the relationship between academic achievement and calibration accuracy, suggesting the need to consider a wide range of factors when explaining performance judgments.

Patterns of everyday technology use and activity involvement in mild cognitive impairment: a five-year follow-up study.

PubMed

Hedman, Annicka; Kottorp, Anders; Nygård, Louise

2018-05-01

The aims were to describe longitudinal patterns in terms of perceived ability to use everyday technology (ET) and involvement in everyday activities over five years in older adults with mild cognitive impairment (MCI), and to examine the predictive value of these patterns regarding diagnostic outcomes. Thirty older adults diagnosed with MCI at inclusion, reported their perceived ability in using ET and involvement in everyday activities on seven occasions over five years. Individual longitudinal case plots and a pattern-oriented analysis were used to compare the participants' distribution in earlier identified stable/ascending, fluctuating and descending patterns of functioning (year 0-2). Fisher's exact test was used for testing the relation between pattern and diagnostic outcomes. An initial descending pattern of functioning tended to continue; none of these participants later developed a more stable pattern. More congruent trajectories of change appeared over time. Pattern affinity years 0-2 and diagnostic outcome were significantly related (p = .05), with a dementia diagnosis being more likely for those initially displaying an early descending pattern Conclusion: These findings point to a need for early support focusing on the use of ET for persons with MCI who early after diagnosis descend in functioning.

A neuropsychological investigation of multitasking in HIV infection: implications for everyday functioning.

PubMed

Scott, J Cobb; Woods, Steven Paul; Vigil, Ofilio; Heaton, Robert K; Schweinsburg, Brian C; Ellis, Ronald J; Grant, Igor; Marcotte, Thomas D

2011-07-01

A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in "real world" functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests' highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection. Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV-). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication). HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV- group. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%). Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals. PsycINFO Database Record (c) 2011 APA, all rights reserved.

A Neuropsychological Investigation of Multitasking in HIV Infection: Implications for Everyday Functioning

PubMed Central

Scott, J. Cobb; Woods, Steven Paul; Vigil, Ofilio; Heaton, Robert K.; Schweinsburg, Brian C.; Ellis, Ronald J.; Grant, Igor; Marcotte, Thomas D.

2010-01-01

Objective A subset of individuals with HIV-associated neurocognitive impairment experience related deficits in “real world” functioning (i.e., independently performing instrumental activities of daily living [IADL]). While performance-based tests of everyday functioning are reasonably sensitive to HIV-associated IADL declines, questions remain regarding the extent to which these tests’ highly structured nature fully captures the inherent complexities of daily life. The aim of this study was to assess the predictive and ecological validity of a novel multitasking measure in HIV infection. Method Participants included 60 individuals with HIV infection (HIV+) and 25 demographically comparable seronegative adults (HIV−). Participants were administered a comprehensive neuropsychological battery, questionnaires assessing mood and everyday functioning, and a novel standardized test of multitasking, which involved balancing the demands of four interconnected performance-based functional tasks (i.e., financial management, cooking, medication management, and telephone communication). Results HIV+ individuals demonstrated significantly worse overall performance, fewer simultaneous task attempts, and increased errors on the multitasking test as compared to the HIV− sample. Within the HIV+ sample, multitasking impairments were modestly associated with deficits on standard neuropsychological measures of executive functions, episodic memory, attention/working memory, and information processing speed, providing preliminary evidence for convergent validity. More importantly, multivariate prediction models revealed that multitasking deficits were uniquely predictive of IADL dependence beyond the effects of depression and global neurocognitive impairment, with excellent sensitivity (86%), but modest specificity (57%). Conclusions Taken together, these data indicate that multitasking ability may play an important role in successful everyday functioning in HIV+ individuals. PMID:21401259

Large-scale De Novo Prediction of Physical Protein-Protein Association*

PubMed Central

Elefsinioti, Antigoni; Saraç, Ömer Sinan; Hegele, Anna; Plake, Conrad; Hubner, Nina C.; Poser, Ina; Sarov, Mihail; Hyman, Anthony; Mann, Matthias; Schroeder, Michael; Stelzl, Ulrich; Beyer, Andreas

2011-01-01

Information about the physical association of proteins is extensively used for studying cellular processes and disease mechanisms. However, complete experimental mapping of the human interactome will remain prohibitively difficult in the near future. Here we present a map of predicted human protein interactions that distinguishes functional association from physical binding. Our network classifies more than 5 million protein pairs predicting 94,009 new interactions with high confidence. We experimentally tested a subset of these predictions using yeast two-hybrid analysis and affinity purification followed by quantitative mass spectrometry. Thus we identified 462 new protein-protein interactions and confirmed the predictive power of the network. These independent experiments address potential issues of circular reasoning and are a distinctive feature of this work. Analysis of the physical interactome unravels subnetworks mediating between different functional and physical subunits of the cell. Finally, we demonstrate the utility of the network for the analysis of molecular mechanisms of complex diseases by applying it to genome-wide association studies of neurodegenerative diseases. This analysis provides new evidence implying TOMM40 as a factor involved in Alzheimer's disease. The network provides a high-quality resource for the analysis of genomic data sets and genetic association studies in particular. Our interactome is available via the hPRINT web server at: www.print-db.org. PMID:21836163

Identification and Classification of Conserved RNA Secondary Structures in the Human Genome

PubMed Central

Pedersen, Jakob Skou; Bejerano, Gill; Siepel, Adam; Rosenbloom, Kate; Lindblad-Toh, Kerstin; Lander, Eric S; Kent, Jim; Miller, Webb; Haussler, David

2006-01-01

The discoveries of microRNAs and riboswitches, among others, have shown functional RNAs to be biologically more important and genomically more prevalent than previously anticipated. We have developed a general comparative genomics method based on phylogenetic stochastic context-free grammars for identifying functional RNAs encoded in the human genome and used it to survey an eight-way genome-wide alignment of the human, chimpanzee, mouse, rat, dog, chicken, zebra-fish, and puffer-fish genomes for deeply conserved functional RNAs. At a loose threshold for acceptance, this search resulted in a set of 48,479 candidate RNA structures. This screen finds a large number of known functional RNAs, including 195 miRNAs, 62 histone 3′UTR stem loops, and various types of known genetic recoding elements. Among the highest-scoring new predictions are 169 new miRNA candidates, as well as new candidate selenocysteine insertion sites, RNA editing hairpins, RNAs involved in transcript auto regulation, and many folds that form singletons or small functional RNA families of completely unknown function. While the rate of false positives in the overall set is difficult to estimate and is likely to be substantial, the results nevertheless provide evidence for many new human functional RNAs and present specific predictions to facilitate their further characterization. PMID:16628248

Viscoplastic Model Development to Account for Strength Differential: Application to Aged Inconel 718 at Elevated Temperature. Degree awarded by Pennsylvania State Univ., 2000

NASA Technical Reports Server (NTRS)

Iyer, Saiganesh; Lerch, Brad (Technical Monitor)

2001-01-01

The magnitude of yield and flow stresses in aged Inconel 718 are observed to be different in tension and compression. This phenomenon, called the Strength differential (SD), contradicts the metal plasticity axiom that the second deviatoric stress invariant alone is sufficient for representing yield and flow. Apparently, at least one of the other two stress invariants is also significant. A unified viscoplastic model was developed that is able to account for the SD effect in aged Inconel 718. Building this model involved both theory and experiments. First, a general threshold function was proposed that depends on all three stress invariants and then the flow and evolution laws were developed using a potential-based thermodynamic framework. Judiciously chosen shear and axial tests were conducted to characterize the material. Shear tests involved monotonic loading, relaxation, and creep tests with different loading rates and load levels. The axial tests were tension and compression tests that resulted in sufficiently large inelastic strains. All tests were performed at 650 C. The viscoplastic material parameters were determined by optimizing the fit to the shear tests, during which the first and the third stress invariants remained zero. The threshold surface parameters were then fit to the tension and compression test data. An experimental procedure was established to quantify the effect of each stress invariant on inelastic deformation. This requires conducting tests with nonproportional three-dimensional load paths. Validation of the model was done using biaxial tests on tubular specimens of aged Inconel 718 using proportional and nonproportional axial-torsion loading. These biaxial tests also helped to determine the most appropriate form of the threshold function; that is, how to combine the stress invariants. Of the set of trial threshold functions, the ones that incorporated the third stress invariant give the best predictions. However, inclusion of the first stress invariant does not significantly improve the model predictions. The model shows excellent predictive capability for nonproportional load paths. Additionally, it reduces to the well-known models of Mises Drucker and Drucker-Prager. The requisite experiments involve reasonably simple load paths in the axial-shear stress plane and hence can be performed on a variety of different materials: be they metallic, geological. polymeric, ceramic or granular. The general form of the threshold function allows representation of inelastic deformation in a range of materials.

A quantitative systems physiology model of renal function and blood pressure regulation: Model description.

PubMed

Hallow, K M; Gebremichael, Y

2017-06-01

Renal function plays a central role in cardiovascular, kidney, and multiple other diseases, and many existing and novel therapies act through renal mechanisms. Even with decades of accumulated knowledge of renal physiology, pathophysiology, and pharmacology, the dynamics of renal function remain difficult to understand and predict, often resulting in unexpected or counterintuitive therapy responses. Quantitative systems pharmacology modeling of renal function integrates this accumulated knowledge into a quantitative framework, allowing evaluation of competing hypotheses, identification of knowledge gaps, and generation of new experimentally testable hypotheses. Here we present a model of renal physiology and control mechanisms involved in maintaining sodium and water homeostasis. This model represents the core renal physiological processes involved in many research questions in drug development. The model runs in R and the code is made available. In a companion article, we present a case study using the model to explore mechanisms and pharmacology of salt-sensitive hypertension. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

Longevity and aging. Mechanisms and perspectives.

PubMed

Labat-Robert, J; Robert, L

2015-12-01

Longevity can mostly be determined with relative accuracy from birth and death registers when available. Aging is a multifactorial process, much more difficult to quantitate. Every measurable physiological function declines with specific speeds over a wide range. The mechanisms involved are also different, genetic factors are of importance for longevity determinations. The best-known genes involved are the Sirtuins, active at the genetic and epigenetic level. Aging is multifactorial, not "coded" in the genome. There are, however, a number of well-studied physical and biological parameters involved in aging, which can be determined and quantitated. We shall try to identify parameters affecting longevity as well as aging and suggest some reasonable predictions for the future. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

White-matter structural connectivity predicts short-term melody and rhythm learning in non-musicians.

PubMed

Vaquero, Lucía; Ramos-Escobar, Neus; François, Clément; Penhune, Virginia; Rodríguez-Fornells, Antoni

2018-06-18

Music learning has received increasing attention in the last decades due to the variety of functions and brain plasticity effects involved during its practice. Most previous reports interpreted the differences between music experts and laymen as the result of training. However, recent investigations suggest that these differences are due to a combination of genetic predispositions with the effect of music training. Here, we tested the relationship of the dorsal auditory-motor pathway with individual behavioural differences in short-term music learning. We gathered structural neuroimaging data from 44 healthy non-musicians (28 females) before they performed a rhythm- and a melody-learning task during a single behavioural session, and manually dissected the arcuate fasciculus (AF) in both hemispheres. The macro- and microstructural organization of the AF (i.e., volume and FA) predicted the learning rate and learning speed in the musical tasks, but only in the right hemisphere. Specifically, the volume of the right anterior segment predicted the synchronization improvement during the rhythm task, the FA in the right long segment was correlated with the learning rate in the melody task, and the volume and FA of the right whole AF predicted the learning speed during the melody task. This is the first study finding a specific relation between different branches within the AF and rhythmic and melodic materials. Our results support the relevant function of the AF as the structural correlate of both auditory-motor transformations and the feedback-feedforward loop, and suggest a crucial involvement of the anterior segment in error-monitoring processes related to auditory-motor learning. These findings have implications for both the neuroscience of music field and second-language learning investigations. Copyright © 2018. Published by Elsevier Inc.

A Machine Learning Method for the Prediction of Receptor Activation in the Simulation of Synapses

PubMed Central

Montes, Jesus; Gomez, Elena; Merchán-Pérez, Angel; DeFelipe, Javier; Peña, Jose-Maria

2013-01-01

Chemical synaptic transmission involves the release of a neurotransmitter that diffuses in the extracellular space and interacts with specific receptors located on the postsynaptic membrane. Computer simulation approaches provide fundamental tools for exploring various aspects of the synaptic transmission under different conditions. In particular, Monte Carlo methods can track the stochastic movements of neurotransmitter molecules and their interactions with other discrete molecules, the receptors. However, these methods are computationally expensive, even when used with simplified models, preventing their use in large-scale and multi-scale simulations of complex neuronal systems that may involve large numbers of synaptic connections. We have developed a machine-learning based method that can accurately predict relevant aspects of the behavior of synapses, such as the percentage of open synaptic receptors as a function of time since the release of the neurotransmitter, with considerably lower computational cost compared with the conventional Monte Carlo alternative. The method is designed to learn patterns and general principles from a corpus of previously generated Monte Carlo simulations of synapses covering a wide range of structural and functional characteristics. These patterns are later used as a predictive model of the behavior of synapses under different conditions without the need for additional computationally expensive Monte Carlo simulations. This is performed in five stages: data sampling, fold creation, machine learning, validation and curve fitting. The resulting procedure is accurate, automatic, and it is general enough to predict synapse behavior under experimental conditions that are different to the ones it has been trained on. Since our method efficiently reproduces the results that can be obtained with Monte Carlo simulations at a considerably lower computational cost, it is suitable for the simulation of high numbers of synapses and it is therefore an excellent tool for multi-scale simulations. PMID:23894367

Computational toxicology using the OpenTox application programming interface and Bioclipse

PubMed Central

2011-01-01

Background Toxicity is a complex phenomenon involving the potential adverse effect on a range of biological functions. Predicting toxicity involves using a combination of experimental data (endpoints) and computational methods to generate a set of predictive models. Such models rely strongly on being able to integrate information from many sources. The required integration of biological and chemical information sources requires, however, a common language to express our knowledge ontologically, and interoperating services to build reliable predictive toxicology applications. Findings This article describes progress in extending the integrative bio- and cheminformatics platform Bioclipse to interoperate with OpenTox, a semantic web framework which supports open data exchange and toxicology model building. The Bioclipse workbench environment enables functionality from OpenTox web services and easy access to OpenTox resources for evaluating toxicity properties of query molecules. Relevant cases and interfaces based on ten neurotoxins are described to demonstrate the capabilities provided to the user. The integration takes advantage of semantic web technologies, thereby providing an open and simplifying communication standard. Additionally, the use of ontologies ensures proper interoperation and reliable integration of toxicity information from both experimental and computational sources. Conclusions A novel computational toxicity assessment platform was generated from integration of two open science platforms related to toxicology: Bioclipse, that combines a rich scriptable and graphical workbench environment for integration of diverse sets of information sources, and OpenTox, a platform for interoperable toxicology data and computational services. The combination provides improved reliability and operability for handling large data sets by the use of the Open Standards from the OpenTox Application Programming Interface. This enables simultaneous access to a variety of distributed predictive toxicology databases, and algorithm and model resources, taking advantage of the Bioclipse workbench handling the technical layers. PMID:22075173

Longitudinal relationships between resources, motivation, and functioning.

PubMed

Hess, Thomas M; Emery, Lisa; Neupert, Shevaun D

2012-05-01

We investigated how fluctuations and linear changes in health and cognitive resources influence the motivation to engage in complex cognitive activity and the extent to which motivation mediated the relationship between changing resources and cognitively demanding activities. Longitudinal data from 332 adults aged 20-85 years were examined. Motivation was assessed using a composite of Need for Cognition and Personal Need for Structure and additional measures of health, sensory functioning, cognitive ability, and self-reported activity engagement. Multilevel modeling revealed that age-typical changes in health, sensory functions, and ability were associated with changes in motivation, with the impact of declining health on motivation being particularly strong in older adulthood. Changes in motivation, in turn, predicted involvement in cognitive and social activities as well as changes in cognitive ability. Finally, motivation was observed to partially mediate the relationship between changes in resources and cognitively demanding activities. Our results suggest that motivation may play an important role in determining the course of cognitive change and involvement in cognitively demanding everyday activities in adulthood.

Basic Helix-Loop-Helix Transcription Factor Gene Family Phylogenetics and Nomenclature

PubMed Central

Skinner, Michael K.; Rawls, Alan; Wilson-Rawls, Jeanne; Roalson, Eric H.

2010-01-01

A phylogenetic analysis of the basic helix-loop-helix (bHLH) gene superfamily was performed using seven different species (human, mouse, rat, worm, fly, yeast, and plant Arabidopsis) and involving over 600 bHLH genes [1]. All bHLH genes were identified in the genomes of the various species, including expressed sequence tags, and the entire coding sequence was used in the analysis. Nearly 15% of the gene family has been updated or added since the original publication. A super-tree involving six clades and all structural relationships was established and is now presented for four of the species. The wealth of functional data available for members of the bHLH gene superfamily provides us with the opportunity to use this exhaustive phylogenetic tree to predict potential functions of uncharacterized members of the family. This phylogenetic and genomic analysis of the bHLH gene family has revealed unique elements of the evolution and functional relationships of the different genes in the bHLH gene family. PMID:20219281

Opportunities of probabilistic flood loss models

NASA Astrophysics Data System (ADS)

Schröter, Kai; Kreibich, Heidi; Lüdtke, Stefan; Vogel, Kristin; Merz, Bruno

2016-04-01

Oftentimes, traditional uni-variate damage models as for instance depth-damage curves fail to reproduce the variability of observed flood damage. However, reliable flood damage models are a prerequisite for the practical usefulness of the model results. Innovative multi-variate probabilistic modelling approaches are promising to capture and quantify the uncertainty involved and thus to improve the basis for decision making. In this study we compare the predictive capability of two probabilistic modelling approaches, namely Bagging Decision Trees and Bayesian Networks and traditional stage damage functions. For model evaluation we use empirical damage data which are available from computer aided telephone interviews that were respectively compiled after the floods in 2002, 2005, 2006 and 2013 in the Elbe and Danube catchments in Germany. We carry out a split sample test by sub-setting the damage records. One sub-set is used to derive the models and the remaining records are used to evaluate the predictive performance of the model. Further we stratify the sample according to catchments which allows studying model performance in a spatial transfer context. Flood damage estimation is carried out on the scale of the individual buildings in terms of relative damage. The predictive performance of the models is assessed in terms of systematic deviations (mean bias), precision (mean absolute error) as well as in terms of sharpness of the predictions the reliability which is represented by the proportion of the number of observations that fall within the 95-quantile and 5-quantile predictive interval. The comparison of the uni-variable Stage damage function and the multivariable model approach emphasises the importance to quantify predictive uncertainty. With each explanatory variable, the multi-variable model reveals an additional source of uncertainty. However, the predictive performance in terms of precision (mbe), accuracy (mae) and reliability (HR) is clearly improved in comparison to uni-variable Stage damage function. Overall, Probabilistic models provide quantitative information about prediction uncertainty which is crucial to assess the reliability of model predictions and improves the usefulness of model results.

An extrapolation method for compressive strength prediction of hydraulic cement products

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

Siqueira Tango, C.E. de

1998-07-01

The basis for the AMEBA Method is presented. A strength-time function is used to extrapolate the predicted cementitious material strength for a late (ALTA) age, based on two earlier age strengths--medium (MEDIA) and low (BAIXA) ages. The experimental basis for the method is data from the IPT-Brazil laboratory and the field, including a long-term study on concrete, research on limestone, slag, and fly-ash additions, and quality control data from a cement factory, a shotcrete tunnel lining, and a grout for structural repair. The method applicability was also verified for high-performance concrete with silica fume. The formula for predicting late agemore » (e.g., 28 days) strength, for a given set of involved ages (e.g., 28,7, and 2 days) is normally a function only of the two earlier ages` (e.g., 7 and 2 days) strengths. This equation has been shown to be independent on materials variations, including cement brand, and is easy to use also graphically. Using the AMEBA method, and only needing to know the type of cement used, it has been possible to predict strengths satisfactorily, even without the preliminary tests which are required in other methods.« less

Studies on scaling of flow noise received at the stagnation point of an axisymmetric body

NASA Astrophysics Data System (ADS)

Arakeri, V. H.; Satyanarayana, S. G.; Mani, K.; Sharma, S. D.

1991-05-01

A description of the studies related to the problem of scaling of flow noise received at the stagnation point of axisymmetric bodies is provided. The source of flow noise under consideration is the transitional/turbulent regions of the boundary layer flow on the axisymmetric body. Lauchle has recently shown that the noise measured in the laminar region (including the stagnation point) corresponds closely to the noise measured in the transition region, provided that the acoustic losses due to diffraction are accounted for. The present study includes experimental measurement of flow noise at the stagnation point of three different shaped axisymmetric headforms. One of the body shapes chosen is that used by Lauchle in similar studies. This was done to establish the effect of body size on flow noise. The results of the experimental investigations clearly show that the flow noise received at the stagnation point is a strong function of free stream velocity, a moderately strong function of body scale but a weak function of boundary layer thickness. In addition, there is evidence that when body scale change is involved, flow noise amplitude scales but no frequency shift is involved. A scaling procedure is proposed based on the present observations along with those of Lauchle. At a given frequency, the amplitude of noise level obtained under model testing conditions is first scaled to account for differences in the velocity and size corresponding to the prototype conditions; then a correction to this is applied to account for losses due to diffraction, which are estimated on the basis of the geometric theory of diffraction (GTD) with the source being located at the predicted position of turbulent transition. Use of the proposed scaling law to extrapolate presently obtained noise levels to two other conditions involving larger-scale bodies show good agreement with actually measured levels, in particular at higher frequencies. Since model scale results have been used successfully to predict levels on larger-sized bodies tested in a totally different environment, the present data along with the proposed scaling procedure can be used to predict the expected flow noise levels at prototype scales during preliminary design studies.

Airway Microbiome Dynamics in Exacerbations of Chronic Obstructive Pulmonary Disease

PubMed Central

Sethi, Sanjay; Murphy, Timothy; Nariya, Snehal; Boushey, Homer A.; Lynch, Susan V.

2014-01-01

Specific bacterial species are implicated in the pathogenesis of exacerbations of chronic obstructive pulmonary disease (COPD). However, recent studies of clinically stable COPD patients have demonstrated a greater diversity of airway microbiota, whose role in acute exacerbations is unclear. In this study, temporal changes in the airway microbiome before, at the onset of, and after an acute exacerbation were examined in 60 sputum samples collected from subjects enrolled in a longitudinal study of bacterial infection in COPD. Microbiome composition and predicted functions were examined using 16S rRNA-based culture-independent profiling methods. Shifts in the abundance (≥2-fold, P < 0.05) of many taxa at exacerbation and after treatment were observed. Microbiota members that were increased at exacerbation were primarily of the Proteobacteria phylum, including nontypical COPD pathogens. Changes in the bacterial composition after treatment for an exacerbation differed significantly among the therapy regimens clinically prescribed (antibiotics only, oral corticosteroids only, or both). Treatment with antibiotics alone primarily decreased the abundance of Proteobacteria, with the prolonged suppression of some microbiota members being observed. In contrast, treatment with corticosteroids alone led to enrichment for Proteobacteria and members of other phyla. Predicted metagenomes of particular microbiota members involved in these compositional shifts indicated exacerbation-associated loss of functions involved in the synthesis of antimicrobial and anti-inflammatory products, alongside enrichment in functions related to pathogen-elicited inflammation. These trends reversed upon clinical recovery. Further larger studies will be necessary to determine whether specific compositional or functional changes detected in the airway microbiome could be useful indicators of exacerbation development or outcome. PMID:24850358

Functional assessment in vocational rehabilitation: a systematic approach to diagnosis and goal setting.

PubMed

Crewe, N M; Athelstan, G T

1981-07-01

The Functional Assessment Inventory (FAI) has been developed for diagnostic use in vocational rehabilitation. This study involved field testing and initial validation of the Inventory as a diagnostic tool. Thirty vocational rehabilitation counselors administered the Inventory to 351 clients. Factor analysis identified 8 scales: Cognitive Function, Motor Function, Personality and Behavior. Vocational Qualifications, Medical Condition, Vision, Hearing, and Economic Disincentives. Content and concurrent validity of the Inventory were assessed by comparing the scores of clients grounded by medical diagnosis and by relating scores to counselors' judgments of severity of disability and employability. Clients with various primary disabilities appeared to differ from one another on the factor scales and on individual items in predictable ways. Total Functional Limitations scores were highly correlated with counselors' ratings of severity of disability and employability.

Computational identification of developmental enhancers:conservation and function of transcription factor binding-site clustersin drosophila melanogaster and drosophila psedoobscura

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

Berman, Benjamin P.; Pfeiffer, Barret D.; Laverty, Todd R.

2004-08-06

Background The identification of sequences that control transcription in metazoans is a major goal of genome analysis. In a previous study, we demonstrated that searching for clusters of predicted transcription factor binding sites could discover active regulatory sequences, and identified 37 regions of the Drosophila melanogaster genome with high densities of predicted binding sites for five transcription factors involved in anterior-posterior embryonic patterning. Nine of these clusters overlapped known enhancers. Here, we report the results of in vivo functional analysis of 27 remaining clusters. Results We generated transgenic flies carrying each cluster attached to a basal promoter and reporter gene,more » and assayed embryos for reporter gene expression. Six clusters are enhancers of adjacent genes: giant, fushi tarazu, odd-skipped, nubbin, squeeze and pdm2; three drive expression in patterns unrelated to those of neighboring genes; the remaining 18 do not appear to have enhancer activity. We used the Drosophila pseudoobscura genome to compare patterns of evolution in and around the 15 positive and 18 false-positive predictions. Although conservation of primary sequence cannot distinguish true from false positives, conservation of binding-site clustering accurately discriminates functional binding-site clusters from those with no function. We incorporated conservation of binding-site clustering into a new genome-wide enhancer screen, and predict several hundred new regulatory sequences, including 85 adjacent to genes with embryonic patterns. Conclusions Measuring conservation of sequence features closely linked to function - such as binding-site clustering - makes better use of comparative sequence data than commonly used methods that examine only sequence identity.« less

Kinesiophobia, Pain, Muscle Functions, and Functional Performances among Older Persons with Low Back Pain.

PubMed

Ishak, Nor Azizah; Zahari, Zarina; Justine, Maria

2017-01-01

This study aims (1) to determine the association between kinesiophobia and pain, muscle functions, and functional performances and (2) to determine whether kinesiophobia predicts pain, muscle functions, and functional performance among older persons with low back pain (LBP). This is a correlational study, involving 63 institutionalized older persons (age = 70.98 ± 7.90 years) diagnosed with LBP. Anthropometric characteristics (BMI) and functional performances (lower limb function, balance and mobility, and hand grip strength) were measured. Muscle strength (abdominal and back muscle strength) was assessed using the Baseline® Mechanical Push/Pull Dynamometer, while muscle control (transverse abdominus and multifidus) was measured by using the Pressure Biofeedback Unit. The pain intensity and the level of kinesiophobia were measured using Numerical Rating Scale and Tampa Scale of Kinesiophobia, respectively. Data were analyzed using Pearson's correlation coefficients and multivariate linear regressions. No significant correlations were found between kinesiophobia and pain and muscle functions (all p > 0.05). Kinesiophobia was significantly correlated with mobility and balance ( p = 0.038, r = 0.263). Regressions analysis showed that kinesiophobia was a significant predictor of mobility and balance ( p = 0.038). We can conclude that kinesiophobia predicted mobility and balance in older persons with LBP. Kinesiophobia should be continuously assessed in clinical settings to recognize the obstacles that may affect patient's compliance towards a rehabilitation program in older persons with LBP.

Kinesiophobia, Pain, Muscle Functions, and Functional Performances among Older Persons with Low Back Pain

PubMed Central

2017-01-01

Objectives This study aims (1) to determine the association between kinesiophobia and pain, muscle functions, and functional performances and (2) to determine whether kinesiophobia predicts pain, muscle functions, and functional performance among older persons with low back pain (LBP). Methods This is a correlational study, involving 63 institutionalized older persons (age = 70.98 ± 7.90 years) diagnosed with LBP. Anthropometric characteristics (BMI) and functional performances (lower limb function, balance and mobility, and hand grip strength) were measured. Muscle strength (abdominal and back muscle strength) was assessed using the Baseline® Mechanical Push/Pull Dynamometer, while muscle control (transverse abdominus and multifidus) was measured by using the Pressure Biofeedback Unit. The pain intensity and the level of kinesiophobia were measured using Numerical Rating Scale and Tampa Scale of Kinesiophobia, respectively. Data were analyzed using Pearson's correlation coefficients and multivariate linear regressions. Results No significant correlations were found between kinesiophobia and pain and muscle functions (all p > 0.05). Kinesiophobia was significantly correlated with mobility and balance (p = 0.038, r = 0.263). Regressions analysis showed that kinesiophobia was a significant predictor of mobility and balance (p = 0.038). Conclusion We can conclude that kinesiophobia predicted mobility and balance in older persons with LBP. Kinesiophobia should be continuously assessed in clinical settings to recognize the obstacles that may affect patient's compliance towards a rehabilitation program in older persons with LBP. PMID:28634547

Can the six-minute walk distance predict the occurrence of acute exacerbations of COPD in patients in Brazil?

PubMed Central

Morakami, Fernanda Kazmierski; Morita, Andrea Akemi; Bisca, Gianna Waldrich; Felcar, Josiane Marques; Ribeiro, Marcos; Furlanetto, Karina Couto; Hernandes, Nidia Aparecida; Pitta, Fabio

2017-01-01

ABSTRACT Objective: To evaluate whether a six-minute walk distance (6MWD) of < 80% of the predicted value can predict the occurrence of acute exacerbations of COPD in patients in Brazil over a 2-year period. Methods: This was a retrospective cross-sectional study involving 50 COPD patients in Brazil. At enrollment, anthropometric data were collected and patients were assessed for pulmonary function (by spirometry) and functional exercise capacity (by the 6MWD). The patients were subsequently divided into two groups: 6MWD ≤ 80% of predicted and 6MWD > 80% of predicted. The occurrence of acute exacerbations of COPD over 2 years was identified by analyzing medical records and contacting patients by telephone. Results: In the sample as a whole, there was moderate-to-severe airflow obstruction (mean FEV1 = 41 ± 12% of predicted) and the mean 6MWD was 469 ± 60 m (86 ± 10% of predicted). Over the 2-year follow-up period, 25 patients (50%) experienced acute exacerbations of COPD. The Kaplan-Meier method showed that the patients in whom the 6MWD was ≤ 80% of predicted were more likely to have exacerbations than were those in whom the 6MWD was > 80% of predicted (p = 0.01), whereas the Cox regression model showed that the former were 2.6 times as likely to have an exacerbation over a 2-year period as were the latter (p = 0.02). Conclusions: In Brazil, the 6MWD can predict acute exacerbations of COPD over a 2-year period. The risk of experiencing an acute exacerbation of COPD within 2 years is more than twice as high in patients in whom the 6MWD is ≤ 80% of predicted. PMID:29365003

Longitudinal Trajectories of Metabolic Control across Adolescence: Associations with Parental Involvement, Adolescents’ Psychosocial Maturity, and Health Care Utilization

PubMed Central

King, Pamela S.; Berg, Cynthia A.; Butner, Jonathan; Drew, Linda M.; Foster, Carol; Donaldson, David; Murray, Mary; Swinyard, Michael; Wiebe, Deborah J.

2012-01-01

Purpose To predict trajectories of metabolic control across adolescence from parental involvement and adolescent psychosocial maturity, and to link metabolic control trajectories to health care utilization. Methods 252 adolescents (M age at study initiation = 12.5, SD=1.5, range 10–14 years) with type 1 diabetes (54.4% female, 92.8% Caucasian, length of diagnosis M=4.7 years, SD=3.0, range 1–12) participated in a 2-year longitudinal study. Metabolic control was gathered from medical records every three months. Adolescents completed measures of self-reliance (functional autonomy and extreme peer orientation), self-control (self-control and externalizing behavior), and parental involvement in diabetes care (acceptance, monitoring, and frequency of help). At the end of the study, mothers reported health care utilization (diabetes-related emergency room visits and hospitalizations) over the past six months. Results Latent class growth analyses indicated two distinct trajectories of metabolic control across adolescence: moderate control with slight deterioration (92% of the sample; average HbA1c = 8.18%) and poor control with rapid deterioration (8% of the sample; average HbA1c of 12.09%). Adolescents with poor and rapidly deteriorating metabolic control reported lower paternal monitoring and frequency of help with diabetes management, lower functional autonomy, and lower self-control than others. Those with poor and rapidly deteriorating metabolic control were 6.4 times more likely to report diabetes-related emergency room visits, and 9.3 times more likely to report diabetes-related hospitalizations near the end of the study. Conclusions Parental involvement and adolescents’ psychosocial maturity predict patterns of deteriorating metabolic control across adolescence and could be targeted for intervention. PMID:22525113

Functional and proteomic analyses reveal that wxcB is involved in virulence, motility, detergent tolerance, and biofilm formation in Xanthomonas campestris pv. vesicatoria.

PubMed

Park, Hye-Jee; Jung, Ho Won; Han, Sang-Wook

2014-09-26

The bacterial envelope possesses diverse functions, including protection against environmental stress and virulence factors for host infection. Here, we report the function of wxcB in Xanthomonas campestris pv. vesicatoria (Xcv), a causal agent of bacterial leaf spot disease in tomato and pepper. To characterize roles of wxcB, we generated a knockout mutant (XcvΔwxcB) and found that the virulence of the mutant was weaker than that of the wild type in tomato plants. To predict the mechanism affected by wxcB, we compared protein expressions between the wild type and the mutant. Expression of 152 proteins showed a greater than 2-fold difference. Proteins involved in motility and cell wall/membrane were the most abundant. Through phenotypic assays, we further demonstrated that the mutant displayed reduced motility and tolerance to treatment, but it showed increased biofilm formation. Interestingly, the LPS profile was unchanged. These results lead to new insights into the functions of wxcB that is associated with cell wall/membrane functions, which contributes to pathogen virulence. Copyright © 2014 Elsevier Inc. All rights reserved.

Perceived functional ability assessed with the spinal function sort: is it valid for European rehabilitation settings in patients with non-specific non-acute low back pain?

PubMed Central

Hilfiker, R.; Kool, J. P.; Bachmann, S.; Hagen, K. B.

2010-01-01

The aim of this study involving 170 patients suffering from non-specific low back pain was to test the validity of the spinal function sort (SFS) in a European rehabilitation setting. The SFS, a picture-based questionnaire, assesses perceived functional ability of work tasks involving the spine. All measurements were taken by a blinded research assistant; work status was assessed with questionnaires. Our study demonstrated a high internal consistency shown by a Cronbach’s alpha of 0.98, reasonable evidence for unidimensionality, spearman correlations of >0.6 with work activities, and discriminating power for work status at 3 and 12 months by ROC curve analysis (area under curve = 0.760 (95% CI 0.689–0.822), respectively, 0.801 (95% CI 0.731–0.859). The standardised response mean within the two treatment groups was 0.18 and −0.31. As a result, we conclude that the perceived functional ability for work tasks can be validly assessed with the SFS in a European rehabilitation setting in patients with non-specific low back pain, and is predictive for future work status. PMID:20490874

Evidence that specific executive functions predict symptom variance among schizophrenia patients with a predominantly negative symptom profile.

PubMed

Donohoe, Gary; Corvin, Aiden; Robertson, Ian H

2006-01-01

Although deficits in executive functioning in schizophrenia have been consistently reported, their precise relationship to symptomatology remains unclear. Recent approaches to executive functioning in nonschizophrenia studies have aimed to "fractionate" the individual cognitive processes involved. In this study, we hypothesised that if these processes are fractionable, then particular symptom syndromes may be selectively related to executive deficits. In particular, it was hoped that this approach could clarify whether negative and positive symptoms of schizophrenia are differentially related to particular aspects of executive/attentional functions. A total of 32 patients with schizophrenia and 16 matched controls were assessed on a series of tasks designed to tap the theoretically derived executive functions of Inhibition, Shifting set, Working memory, and Sustained attention. Negative symptoms were significantly predicted by performance on an "Inhibition" task (Stroop), and not by performance on any other task. Furthermore, for a subgroup of patients with predominantly negative symptoms variance in positive symptoms was only significantly predicted by performance on a set-shifting task (Visual Elevator), and not by performance on other tasks, including inhibition. Our results support the contention that negative symptoms can, at least partly, be conceived of as cognitive behaviours expressing specific executive deficits. Specifically, we discuss the possibility that negative symptoms may, in part, express a failure in response monitoring. We further suggest that the disordered metacognition resulting in positive symptoms may be mediated by cognitive flexibility in patients with a predominantly negative symptom profile.

dPotFit: A computer program to fit diatomic molecule spectral data to potential energy functions

NASA Astrophysics Data System (ADS)

Le Roy, Robert J.

2017-01-01

This paper describes program dPotFit, which performs least-squares fits of diatomic molecule spectroscopic data consisting of any combination of microwave, infrared or electronic vibrational bands, fluorescence series, and tunneling predissociation level widths, involving one or more electronic states and one or more isotopologs, and for appropriate systems, second virial coefficient data, to determine analytic potential energy functions defining the observed levels and other properties of each state. Four families of analytical potential functions are available for fitting in the current version of dPotFit: the Expanded Morse Oscillator (EMO) function, the Morse/Long-Range (MLR) function, the Double-Exponential/Long-Range (DELR) function, and the 'Generalized Potential Energy Function' (GPEF) of Šurkus, which incorporates a variety of polynomial functional forms. In addition, dPotFit allows sets of experimental data to be tested against predictions generated from three other families of analytic functions, namely, the 'Hannover Polynomial' (or "X-expansion") function, and the 'Tang-Toennies' and Scoles-Aziz 'HFD', exponential-plus-van der Waals functions, and from interpolation-smoothed pointwise potential energies, such as those obtained from ab initio or RKR calculations. dPotFit also allows the fits to determine atomic-mass-dependent Born-Oppenheimer breakdown functions, and singlet-state Λ-doubling, or 2Σ splitting radial strength functions for one or more electronic states. dPotFit always reports both the 95% confidence limit uncertainty and the "sensitivity" of each fitted parameter; the latter indicates the number of significant digits that must be retained when rounding fitted parameters, in order to ensure that predictions remain in full agreement with experiment. It will also, if requested, apply a "sequential rounding and refitting" procedure to yield a final parameter set defined by a minimum number of significant digits, while ensuring no significant loss of accuracy in the predictions yielded by those parameters.

The influence of abuse victimization on attendance and involvement in mutual-help groups among dually diagnosed male veterans.

PubMed

Makin-Byrd, Kerry; Cronkite, Ruth C; Timko, Christine

2011-07-01

Although abuse victimization and dual diagnosis are associated with poor functioning across numerous domains, their impact on attendance and involvement in mutual-help groups (MHGs) is not well understood. This study examined the impact of physical or sexual abuse victimization on MHG attendance and involvement and the influence of abuse on the association between MHG involvement and outcomes of abstinence and psychiatric health. Participants were 217 dually diagnosed men assessed at intake into mental health treatment and 6 months later. Compared with nonabused patients, sexually abused patients exhibited more substance use, psychiatric, and social problems at baseline and attended and were involved with MHGs more than nonabused patients at follow-up. Moreover, MHG involvement was most predictive of abstinence for sexually abused patients, as compared with nonabused and physically abused patients. Although dually diagnosed patients with abuse histories demonstrate more severe initial problems, they are likely to utilize MHGs, which may benefit efforts to achieve abstinence. Published by Elsevier Inc.

The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

PubMed

Mackiewicz, Kristen L; Sarinopoulos, Issidoros; Cleven, Krystal L; Nitschke, Jack B

2006-09-19

Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

Prediction of biological functions on glycosylation site migrations in human influenza H1N1 viruses.

PubMed

Sun, Shisheng; Wang, Qinzhe; Zhao, Fei; Chen, Wentian; Li, Zheng

2012-01-01

Protein glycosylation alteration is typically employed by various viruses for escaping immune pressures from their hosts. Our previous work had shown that not only the increase of glycosylation sites (glycosites) numbers, but also glycosite migration might be involved in the evolution of human seasonal influenza H1N1 viruses. More importantly, glycosite migration was likely a more effectively alteration way for the host adaption of human influenza H1N1 viruses. In this study, we provided more bioinformatics and statistic evidences for further predicting the significant biological functions of glycosite migration in the host adaptation of human influenza H1N1 viruses, by employing homology modeling and in silico protein glycosylation of representative HA and NA proteins as well as amino acid variability analysis at antigenic sites of HA and NA. The results showed that glycosite migrations in human influenza viruses have at least five possible functions: to more effectively mask the antigenic sites, to more effectively protect the enzymatic cleavage sites of neuraminidase (NA), to stabilize the polymeric structures, to regulate the receptor binding and catalytic activities and to balance the binding activity of hemagglutinin (HA) with the release activity of NA. The information here can provide some constructive suggestions for the function research related to protein glycosylation of influenza viruses, although these predictions still need to be supported by experimental data.

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

PubMed

Rowe, P S; Oudet, C L; Francis, F; Sinding, C; Pannetier, S; Econs, M J; Strom, T M; Meitinger, T; Garabedian, M; David, A; Macher, M A; Questiaux, E; Popowska, E; Pronicka, E; Read, A P; Mokrzycki, A; Glorieux, F H; Drezner, M K; Hanauer, A; Lehrach, H; Goulding, J N; O'Riordan, J L

1997-04-01

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

Metagenomic Functional Potential Predicts Degradation Rates of a Model Organophosphorus Xenobiotic in Pesticide Contaminated Soils

PubMed Central

Jeffries, Thomas C.; Rayu, Smriti; Nielsen, Uffe N.; Lai, Kaitao; Ijaz, Ali; Nazaries, Loic; Singh, Brajesh K.

2018-01-01

Chemical contamination of natural and agricultural habitats is an increasing global problem and a major threat to sustainability and human health. Organophosphorus (OP) compounds are one major class of contaminant and can undergo microbial degradation, however, no studies have applied system-wide ecogenomic tools to investigate OP degradation or use metagenomics to understand the underlying mechanisms of biodegradation in situ and predict degradation potential. Thus, there is a lack of knowledge regarding the functional genes and genomic potential underpinning degradation and community responses to contamination. Here we address this knowledge gap by performing shotgun sequencing of community DNA from agricultural soils with a history of pesticide usage and profiling shifts in functional genes and microbial taxa abundance. Our results showed two distinct groups of soils defined by differing functional and taxonomic profiles. Degradation assays suggested that these groups corresponded to the organophosphorus degradation potential of soils, with the fastest degrading community being defined by increases in transport and nutrient cycling pathways and enzymes potentially involved in phosphorus metabolism. This was against a backdrop of taxonomic community shifts potentially related to contamination adaptation and reflecting the legacy of exposure. Overall our results highlight the value of using holistic system-wide metagenomic approaches as a tool to predict microbial degradation in the context of the ecology of contaminated habitats. PMID:29515526

Auditory Time-Frequency Masking for Spectrally and Temporally Maximally-Compact Stimuli

PubMed Central

Laback, Bernhard; Savel, Sophie; Ystad, Sølvi; Balazs, Peter; Meunier, Sabine; Kronland-Martinet, Richard

2016-01-01

Many audio applications perform perception-based time-frequency (TF) analysis by decomposing sounds into a set of functions with good TF localization (i.e. with a small essential support in the TF domain) using TF transforms and applying psychoacoustic models of auditory masking to the transform coefficients. To accurately predict masking interactions between coefficients, the TF properties of the model should match those of the transform. This involves having masking data for stimuli with good TF localization. However, little is known about TF masking for mathematically well-localized signals. Most existing masking studies used stimuli that are broad in time and/or frequency and few studies involved TF conditions. Consequently, the present study had two goals. The first was to collect TF masking data for well-localized stimuli in humans. Masker and target were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one critical band. The overall pattern of results is qualitatively similar to existing data for long maskers. To facilitate implementation in audio processing algorithms, a dataset provides the measured TF masking function. The second goal was to assess the potential effect of auditory efferents on TF masking using a modeling approach. The temporal window model of masking was used to predict present and existing data in two configurations: (1) with standard model parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate the activation of efferents. The ability of the model to predict the present data was quite good with the standard configuration but highly degraded with gain reduction. Conversely, the ability of the model to predict existing data for long maskers was better with than without gain reduction. Overall, the model predictions suggest that TF masking can be affected by efferent (or other) effects that reduce cochlear gain. Such effects were avoided in the experiment of this study by using maximally-compact stimuli. PMID:27875575

Auditory Time-Frequency Masking for Spectrally and Temporally Maximally-Compact Stimuli.

PubMed

Necciari, Thibaud; Laback, Bernhard; Savel, Sophie; Ystad, Sølvi; Balazs, Peter; Meunier, Sabine; Kronland-Martinet, Richard

2016-01-01

Many audio applications perform perception-based time-frequency (TF) analysis by decomposing sounds into a set of functions with good TF localization (i.e. with a small essential support in the TF domain) using TF transforms and applying psychoacoustic models of auditory masking to the transform coefficients. To accurately predict masking interactions between coefficients, the TF properties of the model should match those of the transform. This involves having masking data for stimuli with good TF localization. However, little is known about TF masking for mathematically well-localized signals. Most existing masking studies used stimuli that are broad in time and/or frequency and few studies involved TF conditions. Consequently, the present study had two goals. The first was to collect TF masking data for well-localized stimuli in humans. Masker and target were 10-ms Gaussian-shaped sinusoids with a bandwidth of approximately one critical band. The overall pattern of results is qualitatively similar to existing data for long maskers. To facilitate implementation in audio processing algorithms, a dataset provides the measured TF masking function. The second goal was to assess the potential effect of auditory efferents on TF masking using a modeling approach. The temporal window model of masking was used to predict present and existing data in two configurations: (1) with standard model parameters (i.e. without efferents), (2) with cochlear gain reduction to simulate the activation of efferents. The ability of the model to predict the present data was quite good with the standard configuration but highly degraded with gain reduction. Conversely, the ability of the model to predict existing data for long maskers was better with than without gain reduction. Overall, the model predictions suggest that TF masking can be affected by efferent (or other) effects that reduce cochlear gain. Such effects were avoided in the experiment of this study by using maximally-compact stimuli.

Juvenile firesetting in Italy: relationship to aggression, psychopathology, personality, self-efficacy, and school functioning.

PubMed

Del Bove, Giannetta; Caprara, Gian Vittorio; Pastorelli, Concetta; Paciello, Marinella

2008-06-01

Despite the fact that juvenile fire involvement is associated with significant injuries and is highly correlated with diverse maladjustment characteristics, firesetting has never been empirically evaluated in Italy. Participants included 567 youth between 11 and 18 years of age. This investigation attempted to address four gaps in the literature. The first objective was to examine how common firesetting behavior is among Italian youth. The second goal was to explore whether in Italy firesetting is associated with other types of psychopathology and later maladjustment. Thirdly, this study sought to extend our knowledge of the personal characteristics of firesetters. Finally, the relationship between firesetting and aggression remains an empirical question. Results suggested that almost one in three Italian youth reported engaging in fire involvement. Moreover, firesetting in Italian youth is associated with significant levels of antisocial behavior and psychopathology. In fact, firesetters-only demonstrated higher levels of most measures of maladjustment than did aggressive-only youth. Finally, the findings of this study suggest that aggressive firesetters are not at higher risk than nonaggressive firesetters. Instead, fire involvement appears to be the most important variable when predicting serious behavioral difficulties and anti-sociality. This highlights the importance of fire involvement in both the assessment and prediction of antisocial behavior and psychosocial adjustment in adolescence.

Quantum cybernetics and its test in “late choice” experiments

NASA Astrophysics Data System (ADS)

Grössing, Gerhard

1986-11-01

A relativistically invariant wave equation for the propagation of wave fronts S = const ( S being the action function) is derived on the basis of a cybernetic model of quantum systems involving “hidden variables”. This equation can be considered both as an expression of Huygens' principle and as a general continuity equation providing a close link between classical and quantum mechanics. Although the theory reproduces ordinary quantum mechanics, there are particular situations providing experimental predictions differing from those existing theories. Such predictions are made for so-called “late choice” experiments, which are modified versions of the familiar “delayed choice” experiments.

Impairment in Occupational Functioning and Adult ADHD: The Predictive Utility of Executive Function (EF) Ratings Versus EF Tests

PubMed Central

Barkley, Russell A.; Murphy, Kevin R.

2010-01-01

Attention deficit hyperactivity disorder (ADHD) is associated with deficits in executive functioning (EF). ADHD in adults is also associated with impairments in major life activities, particularly occupational functioning. We investigated the extent to which EF deficits assessed by both tests and self-ratings contributed to the degree of impairment in 11 measures involving self-reported occupational problems, employer reported workplace adjustment, and clinician rated occupational adjustment. Three groups of adults were recruited as a function of their severity of ADHD: ADHD diagnosis (n = 146), clinical controls self-referring for ADHD but not diagnosed with it (n = 97), and community controls (n = 109). Groups were combined and regression analyses revealed that self-ratings of EF were significantly predictive of impairments in all 11 measures of occupational adjustment. Although several tests of EF also did so, they contributed substantially less than did the EF ratings, particularly when analyzed jointly with the ratings. We conclude that EF deficits contribute to the impairments in occupational functioning that occur in conjunction with adult ADHD. Ratings of EF in daily life contribute more to such impairments than do EF tests, perhaps because, as we hypothesize, each assesses a different level in the hierarchical organization of EF as a meta-construct. PMID:20197297

Bacterial endophyte communities of three agricultural important grass species differ in their response towards management regimes

NASA Astrophysics Data System (ADS)

Wemheuer, Franziska; Kaiser, Kristin; Karlovsky, Petr; Daniel, Rolf; Vidal, Stefan; Wemheuer, Bernd

2017-01-01

Endophytic bacteria are critical for plant growth and health. However, compositional and functional responses of bacterial endophyte communities towards agricultural practices are still poorly understood. Hence, we analyzed the influence of fertilizer application and mowing frequency on bacterial endophytes in three agriculturally important grass species. For this purpose, we examined bacterial endophytic communities in aerial plant parts of Dactylis glomerata L., Festuca rubra L., and Lolium perenne L. by pyrotag sequencing of bacterial 16S rRNA genes over two consecutive years. Although management regimes influenced endophyte communities, observed responses were grass species-specific. This might be attributed to several bacteria specifically associated with a single grass species. We further predicted functional profiles from obtained 16S rRNA data. These profiles revealed that predicted abundances of genes involved in plant growth promotion or nitrogen metabolism differed between grass species and between management regimes. Moreover, structural and functional community patterns showed no correlation to each other indicating that plant species-specific selection of endophytes is driven by functional rather than phylogenetic traits. The unique combination of 16S rRNA data and functional profiles provided a holistic picture of compositional and functional responses of bacterial endophytes in agricultural relevant grass species towards management practices.

Genetic Adaptation to Climate in White Spruce Involves Small to Moderate Allele Frequency Shifts in Functionally Diverse Genes.

PubMed

Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

2015-11-11

Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome.Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs.Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Genetic Adaptation to Climate in White Spruce Involves Small to Moderate Allele Frequency Shifts in Functionally Diverse Genes

PubMed Central

Hornoy, Benjamin; Pavy, Nathalie; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

2015-01-01

Understanding the genetic basis of adaptation to climate is of paramount importance for preserving and managing genetic diversity in plants in a context of climate change. Yet, this objective has been addressed mainly in short-lived model species. Thus, expanding knowledge to nonmodel species with contrasting life histories, such as forest trees, appears necessary. To uncover the genetic basis of adaptation to climate in the widely distributed boreal conifer white spruce (Picea glauca), an environmental association study was conducted using 11,085 single nucleotide polymorphisms representing 7,819 genes, that is, approximately a quarter of the transcriptome. Linear and quadratic regressions controlling for isolation-by-distance, and the Random Forest algorithm, identified several dozen genes putatively under selection, among which 43 showed strongest signals along temperature and precipitation gradients. Most of them were related to temperature. Small to moderate shifts in allele frequencies were observed. Genes involved encompassed a wide variety of functions and processes, some of them being likely important for plant survival under biotic and abiotic environmental stresses according to expression data. Literature mining and sequence comparison also highlighted conserved sequences and functions with angiosperm homologs. Our results are consistent with theoretical predictions that local adaptation involves genes with small frequency shifts when selection is recent and gene flow among populations is high. Accordingly, genetic adaptation to climate in P. glauca appears to be complex, involving many independent and interacting gene functions, biochemical pathways, and processes. From an applied perspective, these results shall lead to specific functional/association studies in conifers and to the development of markers useful for the conservation of genetic resources. PMID:26560341

A predictive universal fractional-order differential model of wall-turbulence

NASA Astrophysics Data System (ADS)

Song, Fangying; Karniadakis, George

2017-11-01

Fractional calculus has been around for centuries but its use in computational since and engineering has emerged only recently. Here we develop a relatively simple one-dimensional model for fully-developed wall-turbulence that involves a fractional operator with variable fractional order. We use available DNS data bases to ``learn'' the function that describes the fractional order, which has a high value at the wall and decays monotonically to an asymptotic value at the centerline. We show that this function is universal upon re-scaling and hence it can be used to predict the mean velocity profile at all Reynolds numbers. We demonstrate the accuracy of our universal fractional model for channel flow at high Reynolds number as well as for pipe flow and we obtain good agreement with the Princeton super-pipe data up to Reynolds numbers 35,000,000. This work was supported by an ARO MURI Number: W911NF-15-1-0562.

Centralized and Decentralized Control for Demand Response

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

Lu, Shuai; Samaan, Nader A.; Diao, Ruisheng

2011-04-29

Demand response has been recognized as an essential element of the smart grid. Frequency response, regulation and contingency reserve functions performed traditionally by generation resources are now starting to involve demand side resources. Additional benefits from demand response include peak reduction and load shifting, which will defer new infrastructure investment and improve generator operation efficiency. Technical approaches designed to realize these functionalities can be categorized into centralized control and decentralized control, depending on where the response decision is made. This paper discusses these two control philosophies and compares their relative advantages and disadvantages in terms of delay time, predictability, complexity,more » and reliability. A distribution system model with detailed household loads and controls is built to demonstrate the characteristics of the two approaches. The conclusion is that the promptness and reliability of decentralized control should be combined with the predictability and simplicity of centralized control to achieve the best performance of the smart grid.« less

Long-term exposure to zero-g and the gastro-intestinal tract function

NASA Technical Reports Server (NTRS)

Mccormack, Percial D.

1989-01-01

The gastrointestinal tract (GIT) function is described with emphasis placed on its important role to smooth, delay, and modify sudden fluid load stress applied to the fluid distribution control system in the body. Two basic components of the GIT are considered: stomach dynamics, which involves storage, mixing, and discharge of food into the intestine after addition of gastric juices; and absorption of water and electrolytes from the small intestine. A dynamic model of these components is described, along with performance characteristics computed consecutively for one g and zero g conditions. The main impact of the zero g condition appears to be through a change in osmotic driven transport across the gut wall. A dramatic change in transport characteristics is predicted with implication for many body systems (the immune system in particular) during long-term exposure to zero g. Experimental measurements in zero g are needed to evaluate these predictions.

Linear dispersion properties of ring velocity distribution functions

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

Vandas, Marek, E-mail: marek.vandas@asu.cas.cz; Hellinger, Petr; Institute of Atmospheric Physics, AS CR, Bocni II/1401, CZ-14100 Prague

2015-06-15

Linear properties of ring velocity distribution functions are investigated. The dispersion tensor in a form similar to the case of a Maxwellian distribution function, but for a general distribution function separable in velocities, is presented. Analytical forms of the dispersion tensor are derived for two cases of ring velocity distribution functions: one obtained from physical arguments and one for the usual, ad hoc ring distribution. The analytical expressions involve generalized hypergeometric, Kampé de Fériet functions of two arguments. For a set of plasma parameters, the two ring distribution functions are compared. At the parallel propagation with respect to the ambientmore » magnetic field, the two ring distributions give the same results identical to the corresponding bi-Maxwellian distribution. At oblique propagation, the two ring distributions give similar results only for strong instabilities, whereas for weak growth rates their predictions are significantly different; the two ring distributions have different marginal stability conditions.« less

Design optimization of natural laminar flow bodies in compressible flow

NASA Technical Reports Server (NTRS)

Dodbele, Simha S.

1992-01-01

An optimization method has been developed to design axisymmetric body shapes such as fuselages, nacelles, and external fuel tanks with increased transition Reynolds numbers in subsonic compressible flow. The new design method involves a constraint minimization procedure coupled with analysis of the inviscid and viscous flow regions and linear stability analysis of the compressible boundary-layer. In order to reduce the computer time, Granville's transition criterion is used to predict boundary-layer transition and to calculate the gradients of the objective function, and linear stability theory coupled with the e(exp n)-method is used to calculate the objective function at the end of each design iteration. Use of a method to design an axisymmetric body with extensive natural laminar flow is illustrated through the design of a tiptank of a business jet. For the original tiptank, boundary layer transition is predicted to occur at a transition Reynolds number of 6.04 x 10(exp 6). For the designed body shape, a transition Reynolds number of 7.22 x 10(exp 6) is predicted using compressible linear stability theory coupled with the e(exp n)-method.

Computational identification of epitopes in the glycoproteins of novel bunyavirus (SFTS virus) recognized by a human monoclonal antibody (MAb 4-5)

NASA Astrophysics Data System (ADS)

Zhang, Wenshuai; Zeng, Xiaoyan; Zhang, Li; Peng, Haiyan; Jiao, Yongjun; Zeng, Jun; Treutlein, Herbert R.

2013-06-01

In this work, we have developed a new approach to predict the epitopes of antigens that are recognized by a specific antibody. Our method is based on the "multiple copy simultaneous search" (MCSS) approach which identifies optimal locations of small chemical functional groups on the surfaces of the antibody, and identifying sequence patterns of peptides that can bind to the surface of the antibody. The identified sequence patterns are then used to search the amino-acid sequence of the antigen protein. The approach was validated by reproducing the binding epitope of HIV gp120 envelop glycoprotein for the human neutralizing antibody as revealed in the available crystal structure. Our method was then applied to predict the epitopes of two glycoproteins of a newly discovered bunyavirus recognized by an antibody named MAb 4-5. These predicted epitopes can be verified by experimental methods. We also discuss the involvement of different amino acids in the antigen-antibody recognition based on the distributions of MCSS minima of different functional groups.

The Prediction of Scattered Broadband Shock-Associated Noise

NASA Technical Reports Server (NTRS)

Miller, Steven A. E.

2015-01-01

A mathematical model is developed for the prediction of scattered broadband shock-associated noise. Model arguments are dependent on the vector Green's function of the linearized Euler equations, steady Reynolds-averaged Navier-Stokes solutions, and the two-point cross-correlation of the equivalent source. The equivalent source is dependent on steady Reynolds-averaged Navier-Stokes solutions of the jet flow, that capture the nozzle geometry and airframe surface. Contours of the time-averaged streamwise velocity component and turbulent kinetic energy are examined with varying airframe position relative to the nozzle exit. Propagation effects are incorporated by approximating the vector Green's function of the linearized Euler equations. This approximation involves the use of ray theory and an assumption that broadband shock-associated noise is relatively unaffected by the refraction of the jet shear layer. A non-dimensional parameter is proposed that quantifies the changes of the broadband shock-associated noise source with varying jet operating condition and airframe position. Scattered broadband shock-associated noise possesses a second set of broadband lobes that are due to the effect of scattering. Presented predictions demonstrate relatively good agreement compared to a wide variety of measurements.

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

Allendorf, M.D.; Arsenlis, A.; Bastasz, R.

Titanium nitride (TiN) films deposited by chemical vapor deposition (CVD) techniques are of interest for a wide range of commercial applications. In this report, the authors describe a mechanism that predicts Tin film growth rates from TiCl{sub 4}/NH{sub 3} mixtures as a function of process parameters, including inlet reactant concentrations, substrate temperatures, reactor pressures, and total gas flow rates. Model predictions were verified by comparison with the results of TiN deposition experiments in the literature and with measurements made in a new stagnation-flow reactor developed for the purpose of testing deposition mechanisms such as this. In addition, they describe abmore » initio calculations that predict thermodynamic properties for titanium-containing compounds. The results of calculations using Moeller-Plesset perturbation theory, density functional theory, and coupled cluster theory are encouraging and suggest that these methods can be used to estimate thermodynamic data that are essential for the development of CVD models involving transition-metal compounds. Finally, measurements of the adsorption and desorption kinetics of NH{sub 3} on TiN films using temperature-programmed desorption are described and their relevance to TiN CVD and mechanism development are discussed.« less

Infrared Multiple Photon Dissociation Spectroscopy of Sodium and Potassium Chlorate Anions

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

Ryan P. Dain; Christopher M. Leavitt; Jos Oomens

2010-01-01

The structures of gas-phase, metal chlorate anions with the formula [M(ClO3)2]-, M=Na and K, were determined using tandem mass spectrometry and infrared multiple photon dissociation (IRMPD) spectroscopy. Structural assignments for both anions are based on comparisons of the experimental vibrational spectra for the two species to those predicted by density functional theory and involve conformations that feature either bidentate or tridentate coordination of the cation by chlorate. Our results strongly suggest that a structure in which both chlorate anions are bidentate ligands is preferred for [Na(ClO3)2]-. However, for [K(ClO3)2]- the best agreement between experimental and theoretical spectra is obtained frommore » a composite of predicted spectra for which the chlorate anions are either both bidentate or both tridentate ligands. In general, we find that the overall accuracy of DFT calculations for prediction of IR spectra is dependent on both functional and basis set, with best agreement achieved using frequencies generated at the B3LYP/6-311+g(3df) level of theory.« less

Infrared multiple photon dissociation spectroscopy of sodium and potassium chlorate anions.

PubMed

Dain, Ryan P; Leavitt, Christopher M; Oomens, Jos; Steill, Jeffrey D; Groenewold, Gary S; Van Stipdonk, Michael J

2010-01-01

The structures of gas-phase, metal chlorate anions with the formula [M(ClO(3))(2)](-), M = Na and K, were determined using tandem mass spectrometry and infrared multiple photon dissociation (IRMPD) spectroscopy. Structural assignments for both anions are based on comparisons of the experimental vibrational spectra for the two species with those predicted by density functional theory (DFT) and involve conformations that feature either bidentate or tridentate coordination of the cation by chlorate. Our results strongly suggest that a structure in which both chlorate anions are bidentate ligands is preferred for [Na(ClO(3))(2)](-). However, for [K(ClO(3))(2)](-) the best agreement between experimental and theoretical spectra is obtained from a composite of predicted spectra for which the chlorate anions are either both bidentate or both tridentate ligands. In general, we find that the overall accuracy of DFT calculations for prediction of IR spectra is dependent on both functional and basis set, with best agreement achieved using frequencies generated at the B3LYP/6-311+g(3df) level of theory. Copyright 2009 John Wiley & Sons, Ltd.

Method for protein structure alignment

DOEpatents

Blankenbecler, Richard; Ohlsson, Mattias; Peterson, Carsten; Ringner, Markus

2005-02-22

This invention provides a method for protein structure alignment. More particularly, the present invention provides a method for identification, classification and prediction of protein structures. The present invention involves two key ingredients. First, an energy or cost function formulation of the problem simultaneously in terms of binary (Potts) assignment variables and real-valued atomic coordinates. Second, a minimization of the energy or cost function by an iterative method, where in each iteration (1) a mean field method is employed for the assignment variables and (2) exact rotation and/or translation of atomic coordinates is performed, weighted with the corresponding assignment variables.

Visually cued motor synchronization: modulation of fMRI activation patterns by baseline condition.

PubMed

Cerasa, Antonio; Hagberg, Gisela E; Bianciardi, Marta; Sabatini, Umberto

2005-01-03

A well-known issue in functional neuroimaging studies, regarding motor synchronization, is to design suitable control tasks able to discriminate between the brain structures involved in primary time-keeper functions and those related to other processes such as attentional effort. The aim of this work was to investigate how the predictability of stimulus onsets in the baseline condition modulates the activity in brain structures related to processes involved in time-keeper functions during the performance of a visually cued motor synchronization task (VM). The rational behind this choice derives from the notion that using different stimulus predictability can vary the subject's attention and the consequently neural activity. For this purpose, baseline levels of BOLD activity were obtained from 12 subjects during a conventional-baseline condition: maintained fixation of the visual rhythmic stimuli presented in the VM task, and a random-baseline condition: maintained fixation of visual stimuli occurring randomly. fMRI analysis demonstrated that while brain areas with a documented role in basic time processing are detected independent of the baseline condition (right cerebellum, bilateral putamen, left thalamus, left superior temporal gyrus, left sensorimotor cortex, left dorsal premotor cortex and supplementary motor area), the ventral premotor cortex, caudate nucleus, insula and inferior frontal gyrus exhibited a baseline-dependent activation. We conclude that maintained fixation of unpredictable visual stimuli can be employed in order to reduce or eliminate neural activity related to attentional components present in the synchronization task.

Relationship between characteristics on magnetic resonance imaging and motor outcomes in children with cerebral palsy and white matter injury.

PubMed

Reid, Susan M; Ditchfield, Michael R; Bracken, Jenny; Reddihough, Dinah S

2015-01-01

In a population cohort of children with white matter injury (WMI) and cerebral palsy (CP), we aimed to describe the magnetic resonance imaging (MRI) characteristics, identify key structure-function relationships, and classify the severity of WMI in a clinically relevant way. Stratified on MRI laterality/symmetry, variables indicating the extent and location of cerebral abnormalities for 272 children with CP and WMI on chronic-phase MRI were related to gross motor function and motor topography using univariable and multivariable approaches. We found that symmetrical involvement, severe WM loss in the hemispheres and corpus callosum, and cerebellar involvement were the strongest predictors of poor gross motor function, but the final model explained only a small proportion of the variability. Bilateral, extensive WM loss was more likely to result in quadriplegia, whereas volume loss in the posterior-mid WM more frequently resulted in diplegia. The extent and location of MRI abnormalities differed according to laterality/symmetry; asymmetry was associated with less extensive hemispheric involvement than symmetrical WMI, and unilateral lesions were more focal and located more anteriorly. In summary, laterality/symmetry of WMI, possibly reflecting different pathogenic mechanisms, together with extent of WM loss and cerebellar abnormality predicted gross motor function in CP, but to a limited extent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stringent homology-based prediction of H. sapiens-M. tuberculosis H37Rv protein-protein interactions

PubMed Central

2014-01-01

Background H. sapiens-M. tuberculosis H37Rv protein-protein interaction (PPI) data are essential for understanding the infection mechanism of the formidable pathogen M. tuberculosis H37Rv. Computational prediction is an important strategy to fill the gap in experimental H. sapiens-M. tuberculosis H37Rv PPI data. Homology-based prediction is frequently used in predicting both intra-species and inter-species PPIs. However, some limitations are not properly resolved in several published works that predict eukaryote-prokaryote inter-species PPIs using intra-species template PPIs. Results We develop a stringent homology-based prediction approach by taking into account (i) differences between eukaryotic and prokaryotic proteins and (ii) differences between inter-species and intra-species PPI interfaces. We compare our stringent homology-based approach to a conventional homology-based approach for predicting host-pathogen PPIs, based on cellular compartment distribution analysis, disease gene list enrichment analysis, pathway enrichment analysis and functional category enrichment analysis. These analyses support the validity of our prediction result, and clearly show that our approach has better performance in predicting H. sapiens-M. tuberculosis H37Rv PPIs. Using our stringent homology-based approach, we have predicted a set of highly plausible H. sapiens-M. tuberculosis H37Rv PPIs which might be useful for many of related studies. Based on our analysis of the H. sapiens-M. tuberculosis H37Rv PPI network predicted by our stringent homology-based approach, we have discovered several interesting properties which are reported here for the first time. We find that both host proteins and pathogen proteins involved in the host-pathogen PPIs tend to be hubs in their own intra-species PPI network. Also, both host and pathogen proteins involved in host-pathogen PPIs tend to have longer primary sequence, tend to have more domains, tend to be more hydrophilic, etc. And the protein domains from both host and pathogen proteins involved in host-pathogen PPIs tend to have lower charge, and tend to be more hydrophilic. Conclusions Our stringent homology-based prediction approach provides a better strategy in predicting PPIs between eukaryotic hosts and prokaryotic pathogens than a conventional homology-based approach. The properties we have observed from the predicted H. sapiens-M. tuberculosis H37Rv PPI network are useful for understanding inter-species host-pathogen PPI networks and provide novel insights for host-pathogen interaction studies. Reviewers This article was reviewed by Michael Gromiha, Narayanaswamy Srinivasan and Thomas Dandekar. PMID:24708540

Rehabilitation of infants with osteogenesis imperfecta.

PubMed

Binder, H

1995-01-01

Experience gained over twelve years of treating infants with Osteogenesis Imperfecta is described. Emphasized are the facts that no child, including those with OI Sillence II, is too severely involved to not benefit at least from positioning to prevent severe secondary deformities; the Sillence classification does not predict functional ability, particularly regarding patiens with type III OI; disuse weakness and osteoporosis due to immobilization may be more handicapping than the underlying disease itself.

A longitudinal study of child sleep in high and low risk families: relationship to early maternal settling strategies and child psychological functioning.

PubMed

Sheridan, Andrew; Murray, Lynne; Cooper, Peter J; Evangeli, Michael; Byram, Victoria; Halligan, Sarah L

2013-03-01

To investigate whether sleep disturbances previously found to characterise high risk infants: (a) persist into childhood; (b) are influenced by early maternal settling strategies and (c) predict cognitive and emotional/behavioural functioning. Mothers experiencing high and low levels of psychosocial adversity (risk) were recruited antenatally and longitudinally assessed with their children. Mothers completed measures of settling strategies and infant sleep postnatally, and at 12 and 18 months, infant age. At five years, child sleep characteristics were measured via an actigraphy and maternal report; IQ and child adjustment were also assessed. Sleep disturbances observed in high-risk infants persisted at five years. Maternal involvement in infant settling was greater in high risk mothers, and predicted less optimal sleep at five years. Poorer five year sleep was associated with concurrent child anxiety/depression and aggression, but there was limited evidence for an influence of early sleep problems. Associations between infant/child sleep characteristics and IQ were also limited. Early maternal over-involvement in infant settling is associated with less optimal sleep in children, which in turn, is related to child adjustment. The findings highlight the importance of supporting parents in the early development of good settling practices, particularly in high-risk populations. Copyright © 2012 Elsevier B.V. All rights reserved.

Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

PubMed Central

Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

2014-01-01

Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

PubMed

Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M

2016-01-01

Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.

Domain fusion analysis by applying relational algebra to protein sequence and domain databases.

PubMed

Truong, Kevin; Ikura, Mitsuhiko

2003-05-06

Domain fusion analysis is a useful method to predict functionally linked proteins that may be involved in direct protein-protein interactions or in the same metabolic or signaling pathway. As separate domain databases like BLOCKS, PROSITE, Pfam, SMART, PRINTS-S, ProDom, TIGRFAMs, and amalgamated domain databases like InterPro continue to grow in size and quality, a computational method to perform domain fusion analysis that leverages on these efforts will become increasingly powerful. This paper proposes a computational method employing relational algebra to find domain fusions in protein sequence databases. The feasibility of this method was illustrated on the SWISS-PROT+TrEMBL sequence database using domain predictions from the Pfam HMM (hidden Markov model) database. We identified 235 and 189 putative functionally linked protein partners in H. sapiens and S. cerevisiae, respectively. From scientific literature, we were able to confirm many of these functional linkages, while the remainder offer testable experimental hypothesis. Results can be viewed at http://calcium.uhnres.utoronto.ca/pi. As the analysis can be computed quickly on any relational database that supports standard SQL (structured query language), it can be dynamically updated along with the sequence and domain databases, thereby improving the quality of predictions over time.

Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

PubMed Central

Chakrabarti, Kausik; Pearson, Michael; Grate, Leslie; Sterne-Weiler, Timothy; Deans, Jonathan; Donohue, John Paul; Ares, Manuel

2007-01-01

As the genomes of more eukaryotic pathogens are sequenced, understanding how molecular differences between parasite and host might be exploited to provide new therapies has become a major focus. Central to cell function are RNA-containing complexes involved in gene expression, such as the ribosome, the spliceosome, snoRNAs, RNase P, and telomerase, among others. In this article we identify by comparative genomics and validate by RNA analysis numerous previously unknown structural RNAs encoded by the Plasmodium falciparum genome, including the telomerase RNA, U3, 31 snoRNAs, as well as previously predicted spliceosomal snRNAs, SRP RNA, MRP RNA, and RNAse P RNA. Furthermore, we identify six new RNA coding genes of unknown function. To investigate the relationships of the RNA coding genes to other genomic features in related parasites, we developed a genome browser for P. falciparum (http://areslab.ucsc.edu/cgi-bin/hgGateway). Additional experiments provide evidence supporting the prediction that snoRNAs guide methylation of a specific position on U4 snRNA, as well as predicting an snRNA promoter element particular to Plasmodium sp. These findings should allow detailed structural comparisons between the RNA components of the gene expression machinery of the parasite and its vertebrate hosts. PMID:17901154

Prediction of primary somatosensory neuron activity during active tactile exploration

PubMed Central

Campagner, Dario; Evans, Mathew Hywel; Bale, Michael Ross; Erskine, Andrew; Petersen, Rasmus Strange

2016-01-01

Primary sensory neurons form the interface between world and brain. Their function is well-understood during passive stimulation but, under natural behaving conditions, sense organs are under active, motor control. In an attempt to predict primary neuron firing under natural conditions of sensorimotor integration, we recorded from primary mechanosensory neurons of awake, head-fixed mice as they explored a pole with their whiskers, and simultaneously measured both whisker motion and forces with high-speed videography. Using Generalised Linear Models, we found that primary neuron responses were poorly predicted by whisker angle, but well-predicted by rotational forces acting on the whisker: both during touch and free-air whisker motion. These results are in apparent contrast to previous studies of passive stimulation, but could be reconciled by differences in the kinematics-force relationship between active and passive conditions. Thus, simple statistical models can predict rich neural activity elicited by natural, exploratory behaviour involving active movement of sense organs. DOI: http://dx.doi.org/10.7554/eLife.10696.001 PMID:26880559

Voidage correction algorithm for unresolved Euler-Lagrange simulations

NASA Astrophysics Data System (ADS)

Askarishahi, Maryam; Salehi, Mohammad-Sadegh; Radl, Stefan

2018-04-01

The effect of grid coarsening on the predicted total drag force and heat exchange rate in dense gas-particle flows is investigated using Euler-Lagrange (EL) approach. We demonstrate that grid coarsening may reduce the predicted total drag force and exchange rate. Surprisingly, exchange coefficients predicted by the EL approach deviate more significantly from the exact value compared to results of Euler-Euler (EE)-based calculations. The voidage gradient is identified as the root cause of this peculiar behavior. Consequently, we propose a correction algorithm based on a sigmoidal function to predict the voidage experienced by individual particles. Our correction algorithm can significantly improve the prediction of exchange coefficients in EL models, which is tested for simulations involving Euler grid cell sizes between 2d_p and 12d_p . It is most relevant in simulations of dense polydisperse particle suspensions featuring steep voidage profiles. For these suspensions, classical approaches may result in an error of the total exchange rate of up to 30%.

Intergenerational transmission of adaptive functioning: a test of the interactionist model of SES and human development.

PubMed

Schofield, Thomas J; Martin, Monica J; Conger, Katherine J; Neppl, Tricia M; Donnellan, M Brent; Conger, Rand D

2011-01-01

The interactionist model (IM) of human development (R. D. Conger & M. B. Donellan, 2007) proposes that the association between socioeconomic status (SES) and human development involves a dynamic interplay that includes both social causation (SES influences human development) and social selection (individual characteristics affect SES). Using a multigenerational data set involving 271 families, the current study finds empirical support for the IM. Adolescent personality characteristics indicative of social competence, goal-setting, hard work, and emotional stability predicted later SES, parenting, and family characteristics that were related to the positive development of a third-generation child. Processes of both social selection and social causation appear to account for the association between SES and dimensions of human development indicative of healthy functioning across multiple generations. © 2011 The Authors. Child Development © 2011 Society for Research in Child Development, Inc.

Factors Affecting Adolescents' Involvement in Cyberbullying: What Divides the 20% from the 80%?

PubMed

Shin, Namin; Ahn, Hwasil

2015-07-01

Despite some variations among cyberbullying studies, about 20% of the youth population surveyed appears to be involved in cyberbullying. Coincidentally, the current study found that exactly 20% of the students surveyed were involved in cyberbullying as bullies (7.8%), victims (7.5%), and bully/victims (4.7%). What divides those 20% from the 80% of noninvolved students? This study aimed to produce a parsimonious and accurate model that can predict the occurrence of involvement in cyberbullying among youth. Data were collected from a questionnaire survey administered to 1,036 students enrolled in secondary schools in South Korea. Stepwise logistic regression (SLR) was carried out to predict the dichotomous dependent variable (involved/noninvolved) with 10 independent variables grouped into three categories: (a) demographic, (b) media-related, and (c) school and psychology factors. The result of the SLR analysis yielded a four-step model including the variables of cyber-confidence, weekday game time, mobile activities, and age as being significant in explaining the 20/80 division (model χ(2)=34.306, df=4, p<0.001, Nagelkerke R(2)=0.071). This finding suggests that younger students who spend more time playing games on weekdays while being more confident in cyberspace and active in using mobile phones are more likely to be involved in cyberbullying than other students. In particular, the construct of cyber-confidence calls for further elaboration and research, given its controversial function with respect to adolescents' involvement in cyberbullying. Also, this study may bring about insights into practical considerations needed for concerned researchers, teachers, and parents to identify who is inside the group involved in cyberbullying so as to help the participating adolescents escape from the circle of cyberbullying.

Workplace harassment/abuse and alcohol-related outcomes: the mediating role of psychological distress.

PubMed

Richman, Judith A; Shinsako, Stephanie A; Rospenda, Kathleen M; Flaherty, Joseph A; Freels, Sally

2002-07-01

This article embraces a tension-reduction or self-medication perspective on alcohol use and misuse. It empirically addresses the role that psychological distress plays in mediating the relationships between harassing and abusive interpersonal experiences in the workplace and altered alcohol use and misuse. A mail survey was completed by 2,038 university employees (1,098 women and 940 men) at two points in time. Specific hypotheses were tested involving (1) the extent to which the onset and chronicity of harassment and abuse predicted varied Wave-2 drinking outcomes, (2) the extent to which the onset and chronicity of harassment and abuse predicted three forms of Wave-2 psychological distress, (3) the associations between Wave-2 psychological distress and drinking outcomes and (4) the extent to which the associations between harassment/abuse and drinking outcomes disappeared when the salient forms of symptomatic distress functioned as control variables. The data showed that harassment and abuse predicted drinking outcomes and psychological distress, and that the associations between harassment/abuse and drinking outcomes were partially mediated by distress. The findings lend support to the tension-reduction perspective and have important implications for intervention and prevention involving workplace harassment and abuse.

Music training, cognition, and personality.

PubMed

Corrigall, Kathleen A; Schellenberg, E Glenn; Misura, Nicole M

2013-01-01

Although most studies that examined associations between music training and cognitive abilities had correlational designs, the prevailing bias is that music training causes improvements in cognition. It is also possible, however, that high-functioning children are more likely than other children to take music lessons, and that they also differ in personality. We asked whether individual differences in cognition and personality predict who takes music lessons and for how long. The participants were 118 adults (Study 1) and 167 10- to 12-year-old children (Study 2). We collected demographic information and measured cognitive ability and the Big Five personality dimensions. As in previous research, cognitive ability was associated with musical involvement even when demographic variables were controlled statistically. Novel findings indicated that personality was associated with musical involvement when demographics and cognitive ability were held constant, and that openness-to-experience was the personality dimension with the best predictive power. These findings reveal that: (1) individual differences influence who takes music lessons and for how long, (2) personality variables are at least as good as cognitive variables at predicting music training, and (3) future correlational studies of links between music training and non-musical ability should account for individual differences in personality.

Time-series modeling and prediction of global monthly absolute temperature for environmental decision making

NASA Astrophysics Data System (ADS)

Ye, Liming; Yang, Guixia; Van Ranst, Eric; Tang, Huajun

2013-03-01

A generalized, structural, time series modeling framework was developed to analyze the monthly records of absolute surface temperature, one of the most important environmental parameters, using a deterministicstochastic combined (DSC) approach. Although the development of the framework was based on the characterization of the variation patterns of a global dataset, the methodology could be applied to any monthly absolute temperature record. Deterministic processes were used to characterize the variation patterns of the global trend and the cyclic oscillations of the temperature signal, involving polynomial functions and the Fourier method, respectively, while stochastic processes were employed to account for any remaining patterns in the temperature signal, involving seasonal autoregressive integrated moving average (SARIMA) models. A prediction of the monthly global surface temperature during the second decade of the 21st century using the DSC model shows that the global temperature will likely continue to rise at twice the average rate of the past 150 years. The evaluation of prediction accuracy shows that DSC models perform systematically well against selected models of other authors, suggesting that DSC models, when coupled with other ecoenvironmental models, can be used as a supplemental tool for short-term (˜10-year) environmental planning and decision making.

Sustained prediction ability of net analyte preprocessing methods using reduced calibration sets. Theoretical and experimental study involving the spectrophotometric analysis of multicomponent mixtures.

PubMed

Goicoechea, H C; Olivieri, A C

2001-07-01

A newly developed multivariate method involving net analyte preprocessing (NAP) was tested using central composite calibration designs of progressively decreasing size regarding the multivariate simultaneous spectrophotometric determination of three active components (phenylephrine, diphenhydramine and naphazoline) and one excipient (methylparaben) in nasal solutions. Its performance was evaluated and compared with that of partial least-squares (PLS-1). Minimisation of the calibration predicted error sum of squares (PRESS) as a function of a moving spectral window helped to select appropriate working spectral ranges for both methods. The comparison of NAP and PLS results was carried out using two tests: (1) the elliptical joint confidence region for the slope and intercept of a predicted versus actual concentrations plot for a large validation set of samples and (2) the D-optimality criterion concerning the information content of the calibration data matrix. Extensive simulations and experimental validation showed that, unlike PLS, the NAP method is able to furnish highly satisfactory results when the calibration set is reduced from a full four-component central composite to a fractional central composite, as expected from the modelling requirements of net analyte based methods.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord.

PubMed

Starr, Lisa R; Hammen, Constance

2016-05-01

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord

PubMed Central

Starr, Lisa R.; Hammen, Constance

2017-01-01

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR), and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. Results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional Correlates of the 5-HTTLPR genotype. PMID:26037034

Systematic Association of Genes to Phenotypes by Genome and Literature Mining

PubMed Central

Jensen, Lars J; Perez-Iratxeta, Carolina; Kaczanowski, Szymon; Hooper, Sean D; Andrade, Miguel A

2005-01-01

One of the major challenges of functional genomics is to unravel the connection between genotype and phenotype. So far no global analysis has attempted to explore those connections in the light of the large phenotypic variability seen in nature. Here, we use an unsupervised, systematic approach for associating genes and phenotypic characteristics that combines literature mining with comparative genome analysis. We first mine the MEDLINE literature database for terms that reflect phenotypic similarities of species. Subsequently we predict the likely genomic determinants: genes specifically present in the respective genomes. In a global analysis involving 92 prokaryotic genomes we retrieve 323 clusters containing a total of 2,700 significant gene–phenotype associations. Some clusters contain mostly known relationships, such as genes involved in motility or plant degradation, often with additional hypothetical proteins associated with those phenotypes. Other clusters comprise unexpected associations; for example, a group of terms related to food and spoilage is linked to genes predicted to be involved in bacterial food poisoning. Among the clusters, we observe an enrichment of pathogenicity-related associations, suggesting that the approach reveals many novel genes likely to play a role in infectious diseases. PMID:15799710

[Complete genome sequencing of polymalic acid-producing strain Aureobasidium pullulans CCTCC M2012223].

PubMed

Wang, Yongkang; Song, Xiaodan; Li, Xiaorong; Yang, Sang-tian; Zou, Xiang

2017-01-04

To explore the genome sequence of Aureobasidium pullulans CCTCC M2012223, analyze the key genes related to the biosynthesis of important metabolites, and provide genetic background for metabolic engineering. Complete genome of A. pullulans CCTCC M2012223 was sequenced by Illumina HiSeq high throughput sequencing platform. Then, fragment assembly, gene prediction, functional annotation, and GO/COG cluster were analyzed in comparison with those of other five A. pullulans varieties. The complete genome sequence of A. pullulans CCTCC M2012223 was 30756831 bp with an average GC content of 47.49%, and 9452 genes were successfully predicted. Genome-wide analysis showed that A. pullulans CCTCC M2012223 had the biggest genome assembly size. Protein sequences involved in the pullulan and polymalic acid pathway were highly conservative in all of six A. pullulans varieties. Although both A. pullulans CCTCC M2012223 and A. pullulans var. melanogenum have a close affinity, some point mutation and inserts were occurred in protein sequences involved in melanin biosynthesis. Genome information of A. pullulans CCTCC M2012223 was annotated and genes involved in melanin, pullulan and polymalic acid pathway were compared, which would provide a theoretical basis for genetic modification of metabolic pathway in A. pullulans.

Structure-function characterization of the human mitochondrial thiamin pyrophosphate transporter (hMTPPT; SLC25A19): Important roles for Ile(33), Ser(34), Asp(37), His(137) and Lys(291).

PubMed

Sabui, Subrata; Subramanian, Veedamali S; Kapadia, Rubina; Said, Hamid M

2016-08-01

Thiamin plays a critical role in cellular energy metabolism. Mammalian cells obtain the vitamin from their surroundings, converted it to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria via a carrier-mediated process that involves the MTPPT (product of the SLC25A19 gene). Previous studies have characterized different physiological/biological aspects of the human MTPPT (hMTPPT), but less is known about structural features that are important for its function. Here, we used a protein-docking model ("Phyre2" and "DockingServer") to predict residues that may be important for function (substrate recognition) of the hMTPPT; we also examined the role of conserved positively-charged residues predicted ("PRALINE") to be in the trans-membrane domains (TMDs) in uptake of the negatively-charged TPP. Among the six residues predicted by the docking model (i.e., Thr(29), Arg(30), Ile(33), Ser(34), Asp(37) and Phe(298)), only Ile(33), Ser(34) and Asp(37) were found to be critical for function. While no change in translational efficiency/protein stability of the Ser(34) mutant was observed, both the Ile(33) and Asp(37) mutants showed a decrease in this parameter(s); there was also a decrease in the expression of the latter two mutants in mitochondria. A need for a polar residue at position 34 of the hMTPPT was evident. Our findings with the positively-charged residues (i.e., His(82), His(137), Lys(231) and Lys(291)) predicted in the TMD showed that His(137) and Lys(291) are important for function (via a role in proper delivery of the protein to mitochondria). These investigations provide important information about the structure-function relationship of the hMTPPT. Copyright © 2016 Elsevier B.V. All rights reserved.

Molecular Phylogeny and Predicted 3D Structure of Plant beta-D-N-Acetylhexosaminidase

PubMed Central

Hossain, Md. Anowar

2014-01-01

beta-D-N-Acetylhexosaminidase, a family 20 glycosyl hydrolase, catalyzes the removal of β-1,4-linked N-acetylhexosamine residues from oligosaccharides and their conjugates. We constructed phylogenetic tree of β-hexosaminidases to analyze the evolutionary history and predicted functions of plant hexosaminidases. Phylogenetic analysis reveals the complex history of evolution of plant β-hexosaminidase that can be described by gene duplication events. The 3D structure of tomato β-hexosaminidase (β-Hex-Sl) was predicted by homology modeling using 1now as a template. Structural conformity studies of the best fit model showed that more than 98% of the residues lie inside the favoured and allowed regions where only 0.9% lie in the unfavourable region. Predicted 3D structure contains 531 amino acids residues with glycosyl hydrolase20b domain-I and glycosyl hydrolase20 superfamily domain-II including the (β/α)8 barrel in the central part. The α and β contents of the modeled structure were found to be 33.3% and 12.2%, respectively. Eleven amino acids were found to be involved in ligand-binding site; Asp(330) and Glu(331) could play important roles in enzyme-catalyzed reactions. The predicted model provides a structural framework that can act as a guide to develop a hypothesis for β-Hex-Sl mutagenesis experiments for exploring the functions of this class of enzymes in plant kingdom. PMID:25165734

CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

PubMed

Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing

2015-03-01

A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Frontal lesions predict response to prism adaptation treatment in spatial neglect: A randomised controlled study.

PubMed

Goedert, Kelly M; Chen, Peii; Foundas, Anne L; Barrett, A M

2018-03-20

Spatial neglect commonly follows right hemisphere stroke. It is defined as impaired contralesional stimulus detection, response, or action, causing functional disability. While prism adaptation treatment is highly promising to promote functional recovery of spatial neglect, not all individuals respond. Consistent with a primary effect of prism adaptation on spatial movements, we previously demonstrated that functional improvement after prism adaptation treatment is linked to frontal lobe lesions. However, that study was a treatment-only study with no randomised control group. The current study randomised individuals with spatial neglect to receive 10 days of prism adaptation treatment or to receive only standard care (control group). Replicating our earlier results, we found that the presence of frontal lesions moderated response to prism adaptation treatment: among prism-treated patients, only those with frontal lesions demonstrated functional improvements in their neglect symptoms. Conversely, among individuals in the standard care control group, the presence of frontal lesions did not modify recovery. These results suggest that further research is needed on how frontal lesions may predict response to prism adaptation treatment. Additionally, the results help elucidate the neural network involved in spatial movement and could be used to aid decisions about treatment.

Iowa Gambling Task Performance and Executive Function Predict Low-income Urban Preadolescents’ Risky Behaviors

PubMed Central

Ursache, Alexandra; Raver, C. Cybele

2015-01-01

This study examines preadolescents’ reports of risk-taking as predicted by two different, but related inhibitory control systems involving sensitivity to reward and loss on the one hand, and higher order processing in the context of cognitive conflict, known as executive functioning (EF), on the other. Importantly, this study examines these processes with a sample of inner-city, low-income preadolescents and as such examines the ways in which these processes may be related to risky behaviors as a function of children's levels of both concurrent and chronic exposure to household poverty. As part of a larger longitudinal study, 382 children (ages 9 -11) provided a self-report of risky behaviors and participated in the Iowa Gambling task, assessing bias for infrequent loss (preference for infrequent, high magnitude versus frequent, low magnitude loss) and the Hearts and Flowers task assessing executive functioning. Results demonstrated that a higher bias for infrequent loss was associated with higher risky behaviors for children who demonstrated lower EF. Furthermore, bias for infrequent loss was most strongly associated with higher risk-taking for children facing highest levels of poverty. Implications for early identification and prevention of risk-taking in inner-city preadolescents are discussed. PMID:26412918

Cre-lox Univector acceptor vectors for functional screening in protoplasts: analysis of Arabidopsis donor cDNAs encoding ABSCISIC ACID INSENSITIVE1-Like protein phosphatases

PubMed Central

Jia, Fan; Gampala, Srinivas S.L.; Mittal, Amandeep; Luo, Qingjun; Rock, Christopher D.

2009-01-01

The 14,200 available full length Arabidopsis thaliana cDNAs in the Universal Plasmid System (UPS) donor vector pUNI51 should be applied broadly and efficiently to leverage a “functional map-space” of homologous plant genes. We have engineered Cre-lox UPS host acceptor vectors (pCR701- 705) with N-terminal epitope tags in frame with the loxH site and downstream from the maize Ubiquitin promoter for use in transient protoplast expression assays and particle bombardment transformation of monocots. As an example of the utility of these vectors, we recombined them with several Arabidopsis cDNAs encoding Ser/Thr protein phosphatase type 2C (PP2Cs) known from genetic studies or predicted by hierarchical clustering meta-analysis to be involved in ABA and stress responses. Our functional results in Zea mays mesophyll protoplasts on ABA-inducible expression effects on the Late Embryogenesis Abundant promoter ProEm:GUS reporter were consistent with predictions and resulted in identification of novel activities of some PP2Cs. Deployment of these vectors can facilitate functional genomics and proteomics and identification of novel gene activities. PMID:19499346

Operator performance and localized muscle fatigue in a simulated space vehicle control task

NASA Technical Reports Server (NTRS)

Lewis, J. L., Jr.

1979-01-01

Fourier transforms in a special purpose computer were utilized to obtain power spectral density functions from electromyograms of the biceps brachii, triceps brachii, brachioradialis, flexor carpi ulnaris, brachialis, and pronator teres in eight subjects performing isometric tracking tasks in two directions utilizing a prototype spacecraft rotational hand controller. Analysis of these spectra in general purpose computers aided in defining muscles involved in performing the task, and yielded a derived measure potentially useful in predicting task termination. The triceps was the only muscle to show significant differences in all possible tests for simple effects in both tasks and, overall, was the most consistently involved of the six muscles. The total power monitored for triceps, biceps, and brachialis dropped to minimal levels across all subjects earlier than for other muscles. However, smaller variances existed for the biceps, brachioradialis, brachialis, and flexor carpi ulnaris muscles and could provide longer predictive times due to smaller standard deviations for a greater population range.

Emotional and psychological distress of persons involved in the care of patients with Alzheimer disease predicts falls and fractures in their care recipients.

PubMed

Maggio, Dario; Ercolani, Sara; Andreani, Sonia; Ruggiero, Carmelinda; Mariani, Elena; Mangialasche, Francesca; Palmari, Nicola; Mecocci, Patrizia

2010-01-01

Elderly patients with dementia have a higher risk of falls and fractures as compared to cognitively intact elderly subjects. To investigate whether psychological distress of the caregiver might predispose older persons with Alzheimer disease (AD) to falls and fractures, we performed a prospective cohort study. A consecutive series of 110 subjects with dementia underwent baseline and follow-up clinical and functional evaluations. The burden of the caregivers was recorded at baseline. Any intervening fall or fracture was ascertained at the 1-year follow-up. The caregiver burden was significantly higher in persons involved in the care of patients with AD who subsequently fell. In a multivariate regression model, the caregiver burden score predicted falls and fractures. Part of the increased risk of falls and fractures in AD might be due to the distress of caregivers, a factor potentially amenable to treatment. Copyright 2010 S. Karger AG, Basel.

The "proactive" model of learning: Integrative framework for model-free and model-based reinforcement learning utilizing the associative learning-based proactive brain concept.

PubMed

Zsuga, Judit; Biro, Klara; Papp, Csaba; Tajti, Gabor; Gesztelyi, Rudolf

2016-02-01

Reinforcement learning (RL) is a powerful concept underlying forms of associative learning governed by the use of a scalar reward signal, with learning taking place if expectations are violated. RL may be assessed using model-based and model-free approaches. Model-based reinforcement learning involves the amygdala, the hippocampus, and the orbitofrontal cortex (OFC). The model-free system involves the pedunculopontine-tegmental nucleus (PPTgN), the ventral tegmental area (VTA) and the ventral striatum (VS). Based on the functional connectivity of VS, model-free and model based RL systems center on the VS that by integrating model-free signals (received as reward prediction error) and model-based reward related input computes value. Using the concept of reinforcement learning agent we propose that the VS serves as the value function component of the RL agent. Regarding the model utilized for model-based computations we turned to the proactive brain concept, which offers an ubiquitous function for the default network based on its great functional overlap with contextual associative areas. Hence, by means of the default network the brain continuously organizes its environment into context frames enabling the formulation of analogy-based association that are turned into predictions of what to expect. The OFC integrates reward-related information into context frames upon computing reward expectation by compiling stimulus-reward and context-reward information offered by the amygdala and hippocampus, respectively. Furthermore we suggest that the integration of model-based expectations regarding reward into the value signal is further supported by the efferent of the OFC that reach structures canonical for model-free learning (e.g., the PPTgN, VTA, and VS). (c) 2016 APA, all rights reserved).

Respiratory health risk assessment of children living close to industrial areas in Indonesia.

PubMed

Salami, Indah R S; As, Zulfikar A; Marselina, Mariana; Roosmini, Dwina

2014-01-01

Industrial areas are considered to have higher risk of air pollution impact especially to children living close to the industry. Two separate industrial areas in Indonesia were compared. The first location was in the area of coal transportation activity in South Kalimantan, and the second location was in the area of Bogor, West Java where used battery processing industry was often found. Fifty children (boys and girls, aged 6-15 years) were involved in South Kalimantan whereas in West Java there were 48 children (boys and girls, aged 10-12 years) involved. The control groups were also studied in both areas. Predicted average daily intake (ADD) of respirable particulate was estimated and respiratory function was measured using spirometer. The study showed that the PM2.5 concentration in industrial area was 3 times higher than those found in the control location. As a result, the predicted ADD of particulate of children living close to industry in South Kalimantan was 25.45±10.55 µg/kg.day whereas in West Java, the ADD was 1.5 times higher. For both studied area, boys' respirable particulate intake was shown to have higher intake than those in girls. Lung function of children revealed that more than 68% of children in the coal transportation area had decreased pulmonary function. The study also noted that some children in West Java had indicated an obstructive and restrictive respiratory condition. The risk of girls having mild lung disease was found to be 1.3 times greater than those in the control group whereas in boys, the risk was 1.9 times than those in control area. Respiratory function of children in West Java study area was considered to worsen by the higher Pb emission from used battery processing activity.

A novel hybrid decomposition-and-ensemble model based on CEEMD and GWO for short-term PM2.5 concentration forecasting

NASA Astrophysics Data System (ADS)

Niu, Mingfei; Wang, Yufang; Sun, Shaolong; Li, Yongwu

2016-06-01

To enhance prediction reliability and accuracy, a hybrid model based on the promising principle of "decomposition and ensemble" and a recently proposed meta-heuristic called grey wolf optimizer (GWO) is introduced for daily PM2.5 concentration forecasting. Compared with existing PM2.5 forecasting methods, this proposed model has improved the prediction accuracy and hit rates of directional prediction. The proposed model involves three main steps, i.e., decomposing the original PM2.5 series into several intrinsic mode functions (IMFs) via complementary ensemble empirical mode decomposition (CEEMD) for simplifying the complex data; individually predicting each IMF with support vector regression (SVR) optimized by GWO; integrating all predicted IMFs for the ensemble result as the final prediction by another SVR optimized by GWO. Seven benchmark models, including single artificial intelligence (AI) models, other decomposition-ensemble models with different decomposition methods and models with the same decomposition-ensemble method but optimized by different algorithms, are considered to verify the superiority of the proposed hybrid model. The empirical study indicates that the proposed hybrid decomposition-ensemble model is remarkably superior to all considered benchmark models for its higher prediction accuracy and hit rates of directional prediction.

Faulty perceptions? The impact of binge drinking history on college women's perceived rape resistance efficacy.

PubMed

McCauley, Jenna L; Calhoun, Karen S

2008-12-01

College women who binge drink are at greater risk than their peers for experiencing an alcohol-involved rape. Evidence suggests that these women commonly underestimate their risk for assault. This study examines college women's perceptions of their rape resistance efficacy in two acquaintance rape scenarios (one involving the woman's alcohol consumption and one not) as a function of their binge drinking and alcohol-involved rape history. Alcohol-involved rape was inversely associated only with efficacy in situations involving alcohol. Binge drinking was differentially predictive of efficacy in the two scenarios, with regular binge drinkers being significantly more likely to have high perceived efficacy in rape scenarios in which they were drinking and significantly less likely than their peers to have high perceived efficacy in rape scenarios in which they weren't drinking. Findings have direct implications for both college drinking and rape risk reduction interventions, highlighting the need to address women's minimization of alcohol's impact on their rape resistance ability.

Identification of interacting proteins of the TaFVE protein involved in spike development in bread wheat.

PubMed

Zheng, Yong-Sheng; Lu, Yu-Qing; Meng, Ying-Ying; Zhang, Rong-Zhi; Zhang, Han; Sun, Jia-Mei; Wang, Mu-Mu; Li, Li-Hui; Li, Ru-Yu

2017-05-01

WD-40 repeat-containing protein MSI4 (FVE)/MSI4 plays important roles in determining flowering time in Arabidopsis. However, its function is unexplored in wheat. In the present study, coimmunoprecipitation and nanoscale liquid chromatography coupled to MS/MS were used to identify FVE in wheat (TaFVE)-interacting or associated proteins. Altogether 89 differentially expressed proteins showed the same downregulated expression trends as TaFVE in wheat line 5660M. Among them, 62 proteins were further predicted to be involved in the interaction network of TaFVE and 11 proteins have been shown to be potential TaFVE interactors based on curated databases and experimentally determined in other species by the STRING. Both yeast two-hybrid assay and bimolecular fluorescence complementation assay showed that histone deacetylase 6 and histone deacetylase 15 directly interacted with TaFVE. Multiple chromatin-remodelling proteins and polycomb group proteins were also identified and predicted to interact with TaFVE. These results showed that TaFVE directly interacted with multiple proteins to form multiple complexes to regulate spike developmental process, e.g. histone deacetylate, chromatin-remodelling and polycomb repressive complex 2 complexes. In addition, multiple flower development regulation factors (e.g. flowering locus K homology domain, flowering time control protein FPA, FY, flowering time control protein FCA, APETALA 1) involved in floral transition were also identified in the present study. Taken together, these results further elucidate the regulatory functions of TaFVE and help reveal the genetic mechanisms underlying wheat spike differentiation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Uric acid as one of the important factors in multifactorial disorders – facts and controversies

PubMed Central

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an “antioxidant”, a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms. PMID:22384520

Uric acid as one of the important factors in multifactorial disorders--facts and controversies.

PubMed

Pasalic, Daria; Marinkovic, Natalija; Feher-Turkovic, Lana

2012-01-01

With considering serum concentration of the uric acid in humans we are observing hyperuricemia and possible gout development. Many epidemiological studies have shown the relationship between the uric acid and different disorders such are obesity, metabolic syndrome, hypertension and coronary artery disease. Clinicians and investigators recognized serum uric acid concentration as very important diagnostic and prognostic factor of many multifactorial disorders. This review presented few clinical conditions which are not directly related to uric acid, but the concentrations of uric acid might have a great impact in observing, monitoring, prognosis and therapy of such disorders. Uric acid is recognized as a marker of oxidative stress. Production of the uric acid includes enzyme xanthine oxidase which is involved in producing of radical-oxigen species (ROS). As by-products ROS have a significant role in the increased vascular oxidative stress and might be involved in atherogenesis. Uric acid may inhibit endothelial function by inhibition of nitric oxide-function under conditions of oxidative stress. Down regulation of nitric oxide and induction of endothelial dysfunction might also be involved in pathogenesis of hypertension. The most important and well evidenced is possible predictive role of uric acid in predicting short-term outcome (mortality) in acute myocardial infarction (AMI) patients and stroke. Nephrolithiasis of uric acid origin is significantly more common among patients with the metabolic syndrome and obesity. On contrary to this, uric acid also acts is an "antioxidant", a free radical scavenger and a chelator of transitional metal ions which are converted to poorly reactive forms.

Risk approximation in decision making: approximative numeric abilities predict advantageous decisions under objective risk.

PubMed

Mueller, Silke M; Schiebener, Johannes; Delazer, Margarete; Brand, Matthias

2018-01-22

Many decision situations in everyday life involve mathematical considerations. In decisions under objective risk, i.e., when explicit numeric information is available, executive functions and abilities to handle exact numbers and ratios are predictors of objectively advantageous choices. Although still debated, exact numeric abilities, e.g., normative calculation skills, are assumed to be related to approximate number processing skills. The current study investigates the effects of approximative numeric abilities on decision making under objective risk. Participants (N = 153) performed a paradigm measuring number-comparison, quantity-estimation, risk-estimation, and decision-making skills on the basis of rapid dot comparisons. Additionally, a risky decision-making task with exact numeric information was administered, as well as tasks measuring executive functions and exact numeric abilities, e.g., mental calculation and ratio processing skills, were conducted. Approximative numeric abilities significantly predicted advantageous decision making, even beyond the effects of executive functions and exact numeric skills. Especially being able to make accurate risk estimations seemed to contribute to superior choices. We recommend approximation skills and approximate number processing to be subject of future investigations on decision making under risk.

Computed Energetics of Nucleotides in Spatial Ribozyme Structures: An Accurate Identification of Functional Regions from Structure

PubMed Central

Torshin, Ivan Y.

2004-01-01

Ribozymes are functionally diverse RNA molecules with intrinsic catalytic activity. Multiple structural and biochemical studies are required to establish which nucleotide bases are involved in the catalysis. The relative energetic properties of the nucleotide bases have been analyzed in a set of the known ribozyme structures. It was found that many of the known catalytic nucleotides can be identified using only the structure without any additional biochemical data. The results of the calculations compare well with the available biochemical data on RNA stability. Extensive in silico mutagenesis suggests that most of the nucleotides in ribozymes stabilize the RNA. The calculations show that relative contribution of the catalytic bases to RNA stability observably differs from contributions of the noncatalytic bases. Distinction between the concepts of “relative stability” and “mutational stability” is suggested. As results of prediction for several models of ribozymes appear to be in agreement with the published data on the potential active site regions, the method can potentially be used for prediction of functional nucleotides from nucleic sequence. PMID:15105962

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology.

PubMed

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-12-16

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses-the so-called transfer function-and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Bacterial community composition and predicted functional ecology of sponges, sediment and seawater from the thousand islands reef complex, West Java, Indonesia.

PubMed

de Voogd, Nicole J; Cleary, Daniel F R; Polónia, Ana R M; Gomes, Newton C M

2015-04-01

In the present study, we assessed the composition of Bacteria in four biotopes namely sediment, seawater and two sponge species (Stylissa massa and Xestospongia testudinaria) at four different reef sites in a coral reef ecosystem in West Java, Indonesia. In addition to this, we used a predictive metagenomic approach to estimate to what extent nitrogen metabolic pathways differed among bacterial communities from different biotopes. We observed marked differences in bacterial composition of the most abundant bacterial phyla, classes and orders among sponge species, water and sediment. Proteobacteria were by far the most abundant phylum in terms of both sequences and Operational Taxonomic Units (OTUs). Predicted counts for genes associated with the nitrogen metabolism suggested that several genes involved in the nitrogen cycle were enriched in sponge samples, including nosZ, nifD, nirK, norB and nrfA genes. Our data show that a combined barcoded pyrosequencing and predictive metagenomic approach can provide novel insights into the potential ecological functions of the microbial communities. Not only is this approach useful for our understanding of the vast microbial diversity found in sponges but also to understand the potential response of microbial communities to environmental change. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Multiple Roles, Balance between Work and Leisure, and Satisfaction with Level of Living.

ERIC Educational Resources Information Center

Danes, Sharon M.

1998-01-01

A study of 513 farm women found that self-esteem, locus of control (LOC), and age predicted role involvement; LOC, age, and role involvement predicted discrepancy in the work-leisure balance. Life satisfaction was predicted by the interaction of self-esteem, LOC, role involvement, and discrepancy. (SK)

Detecting uber-operons in prokaryotic genomes.

PubMed

Che, Dongsheng; Li, Guojun; Mao, Fenglou; Wu, Hongwei; Xu, Ying

2006-01-01

We present a study on computational identification of uber-operons in a prokaryotic genome, each of which represents a group of operons that are evolutionarily or functionally associated through operons in other (reference) genomes. Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution. Our prediction algorithm predicts uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes. Using this algorithm, we have predicted uber-operons for each of a group of 91 genomes, using the other 90 genomes as references. In particular, we predicted 158 uber-operons in Escherichia coli K12 covering 1830 genes, and found that many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments. For some of the predicted uber-operons that are not parts of known regulons or pathways, our analyses indicate that their genes are highly likely to work together in the same biological processes, suggesting the possibility of new regulons and pathways. We believe that our uber-operon prediction provides a highly useful capability and a rich information source for elucidation of complex biological processes, such as pathways in microbes. All the prediction results are available at our Uber-Operon Database: http://csbl.bmb.uga.edu/uber, the first of its kind.

Detecting uber-operons in prokaryotic genomes

PubMed Central

Che, Dongsheng; Li, Guojun; Mao, Fenglou; Wu, Hongwei; Xu, Ying

2006-01-01

We present a study on computational identification of uber-operons in a prokaryotic genome, each of which represents a group of operons that are evolutionarily or functionally associated through operons in other (reference) genomes. Uber-operons represent a rich set of footprints of operon evolution, whose full utilization could lead to new and more powerful tools for elucidation of biological pathways and networks than what operons have provided, and a better understanding of prokaryotic genome structures and evolution. Our prediction algorithm predicts uber-operons through identifying groups of functionally or transcriptionally related operons, whose gene sets are conserved across the target and multiple reference genomes. Using this algorithm, we have predicted uber-operons for each of a group of 91 genomes, using the other 90 genomes as references. In particular, we predicted 158 uber-operons in Escherichia coli K12 covering 1830 genes, and found that many of the uber-operons correspond to parts of known regulons or biological pathways or are involved in highly related biological processes based on their Gene Ontology (GO) assignments. For some of the predicted uber-operons that are not parts of known regulons or pathways, our analyses indicate that their genes are highly likely to work together in the same biological processes, suggesting the possibility of new regulons and pathways. We believe that our uber-operon prediction provides a highly useful capability and a rich information source for elucidation of complex biological processes, such as pathways in microbes. All the prediction results are available at our Uber-Operon Database: , the first of its kind. PMID:16682449

Functional network architecture predicts psychologically mediated analgesia related to treatment in chronic knee pain patients.

PubMed

Hashmi, Javeria Ali; Kong, Jian; Spaeth, Rosa; Khan, Sheraz; Kaptchuk, Ted J; Gollub, Randy L

2014-03-12

Placebo analgesia is an indicator of how efficiently the brain translates psychological signals conveyed by a treatment procedure into pain relief. It has been demonstrated that functional connectivity between distributed brain regions predicts placebo analgesia in chronic back pain patients. Greater network efficiency in baseline brain networks may allow better information transfer and facilitate adaptive physiological responses to psychological aspects of treatment. Here, we theorized that topological network alignments in resting state scans predict psychologically conditioned analgesic responses to acupuncture treatment in chronic knee osteoarthritis pain patients (n = 45). Analgesia was induced by building positive expectations toward acupuncture treatment with verbal suggestion and heat pain conditioning on a test site of the arm. This procedure induced significantly more analgesia after sham or real acupuncture on the test site than in a control site. The psychologically conditioned analgesia was invariant to sham versus real treatment. Efficiency of information transfer within local networks calculated with graph-theoretic measures (local efficiency and clustering coefficients) significantly predicted conditioned analgesia. Clustering coefficients in regions associated with memory, motivation, and pain modulation were closely involved in predicting analgesia. Moreover, women showed higher clustering coefficients and marginally greater pain reduction than men. Overall, analgesic response to placebo cues can be predicted from a priori resting state data by observing local network topology. Such low-cost synchronizations may represent preparatory resources that facilitate subsequent performance of brain circuits in responding to adaptive environmental cues. This suggests a potential utility of network measures in predicting placebo response for clinical use.

Early-Course Unmedicated Schizophrenia Patients Exhibit Elevated Prefrontal Connectivity Associated with Longitudinal Change

PubMed Central

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W.; Savic, Aleksandar; Yang, Genevieve J.; Repovs, Grega; Murray, John D.; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H.

2015-01-01

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for “hypoconnectivity.” At the whole-brain level, we observed “hyperconnectivity” around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. PMID:25568120

Early-course unmedicated schizophrenia patients exhibit elevated prefrontal connectivity associated with longitudinal change.

PubMed

Anticevic, Alan; Hu, Xinyu; Xiao, Yuan; Hu, Junmei; Li, Fei; Bi, Feng; Cole, Michael W; Savic, Aleksandar; Yang, Genevieve J; Repovs, Grega; Murray, John D; Wang, Xiao-Jing; Huang, Xiaoqi; Lui, Su; Krystal, John H; Gong, Qiyong

2015-01-07

Strong evidence implicates prefrontal cortex (PFC) as a major source of functional impairment in severe mental illness such as schizophrenia. Numerous schizophrenia studies report deficits in PFC structure, activation, and functional connectivity in patients with chronic illness, suggesting that deficient PFC functional connectivity occurs in this disorder. However, the PFC functional connectivity patterns during illness onset and its longitudinal progression remain uncharacterized. Emerging evidence suggests that early-course schizophrenia involves increased PFC glutamate, which might elevate PFC functional connectivity. To test this hypothesis, we examined 129 non-medicated, human subjects diagnosed with early-course schizophrenia and 106 matched healthy human subjects using both whole-brain data-driven and hypothesis-driven PFC analyses of resting-state fMRI. We identified increased PFC connectivity in early-course patients, predictive of symptoms and diagnostic classification, but less evidence for "hypoconnectivity." At the whole-brain level, we observed "hyperconnectivity" around areas centered on the default system, with modest overlap with PFC-specific effects. The PFC hyperconnectivity normalized for a subset of the sample followed longitudinally (n = 25), which also predicted immediate symptom improvement. Biologically informed computational modeling implicates altered overall connection strength in schizophrenia. The initial hyperconnectivity, which may decrease longitudinally, could have prognostic and therapeutic implications. Copyright © 2015 the authors 0270-6474/15/350267-20$15.00/0.

Functional brain networks for learning predictive statistics.

PubMed

Giorgio, Joseph; Karlaftis, Vasilis M; Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew; Kourtzi, Zoe

2017-08-18

Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Actinobacterial Acyl Coenzyme A Synthetases Involved in Steroid Side-Chain Catabolism

PubMed Central

Casabon, Israël; Swain, Kendra; Crowe, Adam M.

2014-01-01

Bacterial steroid catabolism is an important component of the global carbon cycle and has applications in drug synthesis. Pathways for this catabolism involve multiple acyl coenzyme A (CoA) synthetases, which activate alkanoate substituents for β-oxidation. The functions of these synthetases are poorly understood. We enzymatically characterized four distinct acyl-CoA synthetases from the cholate catabolic pathway of Rhodococcus jostii RHA1 and the cholesterol catabolic pathway of Mycobacterium tuberculosis. Phylogenetic analysis of 70 acyl-CoA synthetases predicted to be involved in steroid metabolism revealed that the characterized synthetases each represent an orthologous class with a distinct function in steroid side-chain degradation. The synthetases were specific for the length of alkanoate substituent. FadD19 from M. tuberculosis H37Rv (FadD19Mtb) transformed 3-oxo-4-cholesten-26-oate (kcat/Km = 0.33 × 105 ± 0.03 × 105 M−1 s−1) and represents orthologs that activate the C8 side chain of cholesterol. Both CasGRHA1 and FadD17Mtb are steroid-24-oyl-CoA synthetases. CasG and its orthologs activate the C5 side chain of cholate, while FadD17 and its orthologs appear to activate the C5 side chain of one or more cholesterol metabolites. CasIRHA1 is a steroid-22-oyl-CoA synthetase, representing orthologs that activate metabolites with a C3 side chain, which accumulate during cholate catabolism. CasI had similar apparent specificities for substrates with intact or extensively degraded steroid nuclei, exemplified by 3-oxo-23,24-bisnorchol-4-en-22-oate and 1β(2′-propanoate)-3aα-H-4α(3″-propanoate)-7aβ-methylhexahydro-5-indanone (kcat/Km = 2.4 × 105 ± 0.1 × 105 M−1 s−1 and 3.2 × 105 ± 0.3 × 105 M−1 s−1, respectively). Acyl-CoA synthetase classes involved in cholate catabolism were found in both Actinobacteria and Proteobacteria. Overall, this study provides insight into the physiological roles of acyl-CoA synthetases in steroid catabolism and a phylogenetic classification enabling prediction of specific functions of related enzymes. PMID:24244004

Prediction of scaffold proteins based on protein interaction and domain architectures.

PubMed

Oh, Kimin; Yi, Gwan-Su

2016-07-28

Scaffold proteins are known for being crucial regulators of various cellular functions by assembling multiple proteins involved in signaling and metabolic pathways. Identification of scaffold proteins and the study of their molecular mechanisms can open a new aspect of cellular systemic regulation and the results can be applied in the field of medicine and engineering. Despite being highlighted as the regulatory roles of dozens of scaffold proteins, there was only one known computational approach carried out so far to find scaffold proteins from interactomes. However, there were limitations in finding diverse types of scaffold proteins because their criteria were restricted to the classical scaffold proteins. In this paper, we will suggest a systematic approach to predict massive scaffold proteins from interactomes and to characterize the roles of scaffold proteins comprehensively. From a total of 10,419 basic scaffold protein candidates in protein interactomes, we classified them into three classes according to the structural evidences for scaffolding, such as domain architectures, domain interactions and protein complexes. Finally, we could define 2716 highly reliable scaffold protein candidates and their characterized functional features. To assess the accuracy of our prediction, the gold standard positive and negative data sets were constructed. We prepared 158 gold standard positive data and 844 gold standard negative data based on the functional information from Gene Ontology consortium. The precision, sensitivity and specificity of our testing was 80.3, 51.0, and 98.5 % respectively. Through the function enrichment analysis of highly reliable scaffold proteins, we could confirm the significantly enriched functions that are related to scaffold protein binding. We also identified functional association between scaffold proteins and their recruited proteins. Furthermore, we checked that the disease association of scaffold proteins is higher than kinases. In conclusion, we could predict larger volume of scaffold proteins and analyzed their functional characteristics. Deeper understandings about the roles of scaffold proteins from this study will provide a higher opportunity to find therapeutic or engineering applications of scaffold proteins using their functional characteristics.

Latent profiles of non-residential father engagement six years after divorce predict long term offspring outcomes

PubMed Central

Modecki, Kathryn Lynn; Hagan, Melissa; Sandler, Irwin; Wolchik, Sharlene

2014-01-01

This study examined profiles of non-residential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) six to eight years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, nine years later. Parental divorce occurred during late childhood to early adolescence; indicators of non-residential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed nine years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes nine years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother’s remarriage, mother’s income, and gender, age and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems nine years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long-term. Implications of findings for policy and intervention are discussed. PMID:24484456

Latent profiles of nonresidential father engagement six years after divorce predict long-term offspring outcomes.

PubMed

Modecki, Kathryn Lynn; Hagan, Melissa J; Sandler, Irwin; Wolchik, Sharlene A

2015-01-01

This study examined profiles of nonresidential father engagement (i.e., support to the adolescent, contact frequency, remarriage, relocation, and interparental conflict) with their adolescent children (N = 156) 6 to 8 years following divorce and the prospective relation between these profiles and the psychosocial functioning of their offspring, 9 years later. Parental divorce occurred during late childhood to early adolescence; indicators of nonresidential father engagement were assessed during adolescence, and mental health problems and academic achievement of offspring were assessed 9 years later in young adulthood. Three profiles of father engagement were identified in our sample of mainly White, non-Hispanic divorced fathers: Moderate Involvement/Low Conflict, Low Involvement/Moderate Conflict, and High Involvement/High Conflict. Profiles differentially predicted offspring outcomes 9 years later when they were young adults, controlling for quality of the mother-adolescent relationship, mother's remarriage, mother's income, and gender, age, and offspring mental health problems in adolescence. Offspring of fathers characterized as Moderate Involvement/Low Conflict had the highest academic achievement and the lowest number of externalizing problems 9 years later compared to offspring whose fathers had profiles indicating either the highest or lowest levels of involvement but higher levels of conflict. Results indicate that greater paternal psychosocial support and more frequent father-adolescent contact do not outweigh the negative impact of interparental conflict on youth outcomes in the long term. Implications of findings for policy and intervention are discussed.

Non sentinel node involvement prediction for sentinel node micrometastases in breast cancer: nomogram validation and comparison with other models.

PubMed

Houvenaeghel, Gilles; Bannier, Marie; Nos, Claude; Giard, Sylvia; Mignotte, Herve; Jacquemier, Jocelyne; Martino, Marc; Esterni, Benjamin; Belichard, Catherine; Classe, Jean-Marc; Tunon de Lara, Christine; Cohen, Monique; Payan, Raoul; Blanchot, Jerome; Rouanet, Philippe; Penault-Llorca, Frederique; Bonnier, Pascal; Fournet, Sandrine; Agostini, Aubert; Marchal, Frederique; Garbay, Jean-Remi

2012-04-01

The risk of non sentinel node (NSN) involvement varies in function of the characteristics of sentinel nodes (SN) and primary tumor. Our aim was to determine and validate a statistical tool (a nomogram) able to predict the risk of NSN involvement in case of SN micro or sub-micrometastasis of breast cancer. We have compared this monogram with other models described in the literature. We have collected data on 905 patients, then 484 other patients, to build and validate the nomogram and compare it with other published scores and nomograms. Multivariate analysis conducted on the data of the first cohort allowed us to define a nomogram based on 5 criteria: the method of SN detection (immunohistochemistry or by standard coloration with HES); the ratio of positive SN out of total removed SN; the pathologic size of the tumor; the histological type; and the presence (or not) of lympho-vascular invasion. The nomogram developed here is the only one dedicated to micrometastasis and developed on the basis of two large cohorts. The results of this statistical tool in the calculation of the risk of NSN involvement is similar to those of the MSKCC (the similarly more effective nomogram according to the literature), with a lower rate of false negatives. this nomogram is dedicated specifically to cases of SN involvement by metastasis lower or equal to 2 mm. It could be used in clinical practice in the way to omit ALND when the risk of NSN involvement is low. Copyright © 2011 Elsevier Ltd. All rights reserved.

Equilibrium Propagation: Bridging the Gap between Energy-Based Models and Backpropagation

PubMed Central

Scellier, Benjamin; Bengio, Yoshua

2017-01-01

We introduce Equilibrium Propagation, a learning framework for energy-based models. It involves only one kind of neural computation, performed in both the first phase (when the prediction is made) and the second phase of training (after the target or prediction error is revealed). Although this algorithm computes the gradient of an objective function just like Backpropagation, it does not need a special computation or circuit for the second phase, where errors are implicitly propagated. Equilibrium Propagation shares similarities with Contrastive Hebbian Learning and Contrastive Divergence while solving the theoretical issues of both algorithms: our algorithm computes the gradient of a well-defined objective function. Because the objective function is defined in terms of local perturbations, the second phase of Equilibrium Propagation corresponds to only nudging the prediction (fixed point or stationary distribution) toward a configuration that reduces prediction error. In the case of a recurrent multi-layer supervised network, the output units are slightly nudged toward their target in the second phase, and the perturbation introduced at the output layer propagates backward in the hidden layers. We show that the signal “back-propagated” during this second phase corresponds to the propagation of error derivatives and encodes the gradient of the objective function, when the synaptic update corresponds to a standard form of spike-timing dependent plasticity. This work makes it more plausible that a mechanism similar to Backpropagation could be implemented by brains, since leaky integrator neural computation performs both inference and error back-propagation in our model. The only local difference between the two phases is whether synaptic changes are allowed or not. We also show experimentally that multi-layer recurrently connected networks with 1, 2, and 3 hidden layers can be trained by Equilibrium Propagation on the permutation-invariant MNIST task. PMID:28522969

Cell-Type-Specific Predictive Network Yields Novel Insights into Mouse Embryonic Stem Cell Self-Renewal and Cell Fate

PubMed Central

Dowell, Karen G.; Simons, Allen K.; Wang, Zack Z.; Yun, Kyuson; Hibbs, Matthew A.

2013-01-01

Self-renewal, the ability of a stem cell to divide repeatedly while maintaining an undifferentiated state, is a defining characteristic of all stem cells. Here, we clarify the molecular foundations of mouse embryonic stem cell (mESC) self-renewal by applying a proven Bayesian network machine learning approach to integrate high-throughput data for protein function discovery. By focusing on a single stem-cell system, at a specific developmental stage, within the context of well-defined biological processes known to be active in that cell type, we produce a consensus predictive network that reflects biological reality more closely than those made by prior efforts using more generalized, context-independent methods. In addition, we show how machine learning efforts may be misled if the tissue specific role of mammalian proteins is not defined in the training set and circumscribed in the evidential data. For this study, we assembled an extensive compendium of mESC data: ∼2.2 million data points, collected from 60 different studies, under 992 conditions. We then integrated these data into a consensus mESC functional relationship network focused on biological processes associated with embryonic stem cell self-renewal and cell fate determination. Computational evaluations, literature validation, and analyses of predicted functional linkages show that our results are highly accurate and biologically relevant. Our mESC network predicts many novel players involved in self-renewal and serves as the foundation for future pluripotent stem cell studies. This network can be used by stem cell researchers (at http://StemSight.org) to explore hypotheses about gene function in the context of self-renewal and to prioritize genes of interest for experimental validation. PMID:23468881

Compared effects of missense mutations in Very-Long-Chain Acyl-CoA Dehydrogenase deficiency: Combined analysis by structural, functional and pharmacological approaches.

PubMed

Gobin-Limballe, Stéphanie; McAndrew, Ryan P; Djouadi, Fatima; Kim, Jung-Ja; Bastin, Jean

2010-05-01

Very-Long-Chain Acyl-CoA Dehydrogenase deficiency (VLCADD) is an autosomal recessive disorder considered as one of the more common ss-oxidation defects, possibly associated with neonatal cardiomyopathy, infantile hepatic coma, or adult-onset myopathy. Numerous gene missense mutations have been described in these VLCADD phenotypes, but only few of them have been structurally and functionally analyzed, and the molecular basis of disease variability is still poorly understood. To address this question, we first analyzed fourteen disease-causing amino acid changes using the recently described crystal structure of VLCAD. The predicted effects varied from the replacement of amino acid residues lining the substrate binding cavity, involved in holoenzyme-FAD interactions or in enzyme dimerisation, predicted to have severe functional consequences, up to amino acid substitutions outside key enzyme domains or lying on near enzyme surface, with predicted milder consequences. These data were combined with functional analysis of residual fatty acid oxidation (FAO) and VLCAD protein levels in patient cells harboring these mutations, before and after pharmacological stimulation by bezafibrate. Mutations identified as detrimental to the protein structure in the 3-D model were generally associated to profound FAO and VLCAD protein deficiencies in the patient cells, however, some mutations affecting FAD binding or monomer-monomer interactions allowed a partial response to bezafibrate. On the other hand, bezafibrate restored near-normal FAO rates in some mutations predicted to have milder consequences on enzyme structure. Overall, combination of structural, biochemical, and pharmacological analysis allowed assessment of the relative severity of individual mutations, with possible applications for disease management and therapeutic approach. Copyright 2010 Elsevier B.V. All rights reserved.

Dynamic Relationships Between Parental Monitoring, Peer Risk Involvement and Sexual Risk Behavior Among Bahamian Mid-Adolescents

PubMed Central

Wang, Bo; Stanton, Bonita; Deveaux, Lynette; Li, Xiaoming; Lunn, Sonja

2015-01-01

CONTEXT Considerable research has examined reciprocal relationships between parenting, peers and adolescent problem behavior; however, such studies have largely considered the influence of peers and parents separately. It is important to examine simultaneously the relationships between parental monitoring, peer risk involvement and adolescent sexual risk behavior, and whether increases in peer risk involvement and changes in parental monitoring longitudinally predict adolescent sexual risk behavior. METHODS Four waves of sexual behavior data were collected between 2008/2009 and 2011 from high school students aged 13–17 in the Bahamas. Structural equation and latent growth curve modeling were used to examine reciprocal relationships between parental monitoring, perceived peer risk involvement and adolescent sexual risk behavior. RESULTS For both male and female youth, greater perceived peer risk involvement predicted higher sexual risk behavior index scores, and greater parental monitoring predicted lower scores. Reciprocal relationships were found between parental monitoring and sexual risk behavior for males and between perceived peer risk involvement and sexual risk behavior for females. For males, greater sexual risk behavior predicted lower parental monitoring; for females, greater sexual risk behavior predicted higher perceived peer risk involvement. According to latent growth curve models, a higher initial level of parental monitoring predicted decreases in sexual risk behavior, whereas both a higher initial level and a higher growth rate of peer risk involvement predicted increases in sexual risk behavior. CONCLUSION Results highlight the important influence of peer risk involvement on youths’ sexual behavior and gender differences in reciprocal relationships between parental monitoring, peer influence and adolescent sexual risk behavior. PMID:26308261

Dynamic Relationships Between Parental Monitoring, Peer Risk Involvement and Sexual Risk Behavior Among Bahamian Mid-Adolescents.

PubMed

Wang, Bo; Stanton, Bonita; Deveaux, Lynette; Li, Xiaoming; Lunn, Sonja

2015-06-01

Considerable research has examined reciprocal relationships between parenting, peers and adolescent problem behavior; however, such studies have largely considered the influence of peers and parents separately. It is important to examine simultaneously the relationships between parental monitoring, peer risk involvement and adolescent sexual risk behavior, and whether increases in peer risk involvement and changes in parental monitoring longitudinally predict adolescent sexual risk behavior. Four waves of sexual behavior data were collected between 2008/2009 and 2011 from high school students aged 13-17 in the Bahamas. Structural equation and latent growth curve modeling were used to examine reciprocal relationships between parental monitoring, perceived peer risk involvement and adolescent sexual risk behavior. For both male and female youth, greater perceived peer risk involvement predicted higher sexual risk behavior index scores, and greater parental monitoring predicted lower scores. Reciprocal relationships were found between parental monitoring and sexual risk behavior for males and between perceived peer risk involvement and sexual risk behavior for females. For males, greater sexual risk behavior predicted lower parental monitoring; for females, greater sexual risk behavior predicted higher perceived peer risk involvement. According to latent growth curve models, a higher initial level of parental monitoring predicted decreases in sexual risk behavior, whereas both a higher initial level and a higher growth rate of peer risk involvement predicted increases in sexual risk behavior. Results highlight the important influence of peer risk involvement on youths' sexual behavior and gender differences in reciprocal relationships between parental monitoring, peer influence and adolescent sexual risk behavior.

Parental childhood adversity, depressive symptoms, and parenting quality: Effects on toddler self-regulation in Child Welfare Services-involved families

PubMed Central

Spieker, Susan J.; Oxford, Monica L.; Fleming, Charles B.; Lohr, Mary Jane

2018-01-01

Parents who are child welfare services-involved (CWSI) often have a history of childhood adversity and depressive symptoms. Both affect parenting quality, which in turn influences child adaptive functioning. We tested a model of the relations between parental depression and child regulatory outcomes first proposed by Lyons-Ruth and colleagues (2002). We hypothesized that both parental depression and parenting quality mediate the effects of parental early adversity on offspring regulatory outcomes. Participants were 123 CWSI parents and their toddlers who were assessed three times over a period of six months. At T1, parents reported on their childhood adversity and current depressive symptoms. At T2, parents’ sensitivity to their child’s distress and non-distress cues were rated from a videotaped teaching task. At T3, observers rated children’s emotional regulation, orientation/engagement, and secure base behavior. The results of a path model partly supported hypotheses. Parent childhood adversity was associated with current depressive symptoms, which in turn was related to parent sensitivity to child distress but not non-distress. Sensitivity to distress also predicted secure base behavior. Depression directly predicted orientation/engagement, also predicted by sensitivity to non-distress. Sensitivity to distress predicted emotion regulation and orientation/engagement. Results are discussed in terms of intervention approaches for CWSI families. PMID:29266280

Hemispheric Asymmetries in Striatal Reward Responses Relate to Approach-Avoidance Learning and Encoding of Positive-Negative Prediction Errors in Dopaminergic Midbrain Regions.

PubMed

Aberg, Kristoffer Carl; Doell, Kimberly C; Schwartz, Sophie

2015-10-28

Some individuals are better at learning about rewarding situations, whereas others are inclined to avoid punishments (i.e., enhanced approach or avoidance learning, respectively). In reinforcement learning, action values are increased when outcomes are better than predicted (positive prediction errors [PEs]) and decreased for worse than predicted outcomes (negative PEs). Because actions with high and low values are approached and avoided, respectively, individual differences in the neural encoding of PEs may influence the balance between approach-avoidance learning. Recent correlational approaches also indicate that biases in approach-avoidance learning involve hemispheric asymmetries in dopamine function. However, the computational and neural mechanisms underpinning such learning biases remain unknown. Here we assessed hemispheric reward asymmetry in striatal activity in 34 human participants who performed a task involving rewards and punishments. We show that the relative difference in reward response between hemispheres relates to individual biases in approach-avoidance learning. Moreover, using a computational modeling approach, we demonstrate that better encoding of positive (vs negative) PEs in dopaminergic midbrain regions is associated with better approach (vs avoidance) learning, specifically in participants with larger reward responses in the left (vs right) ventral striatum. Thus, individual dispositions or traits may be determined by neural processes acting to constrain learning about specific aspects of the world. Copyright © 2015 the authors 0270-6474/15/3514491-10$15.00/0.

PARENTAL CHILDHOOD ADVERSITY, DEPRESSIVE SYMPTOMS, AND PARENTING QUALITY: EFFECTS ON TODDLER SELF-REGULATION IN CHILD WELFARE SERVICES INVOLVED FAMILIES.

PubMed

Spieker, Susan J; Oxford, Monica L; Fleming, Charles B; Lohr, Mary Jane

2018-01-01

Parents who are involved with child welfare services (CWSI) often have a history of childhood adversity and depressive symptoms. Both affect parenting quality, which in turn influences child adaptive functioning. We tested a model of the relations between parental depression and child regulatory outcomes first proposed by K. Lyons-Ruth, R. Wolfe, A. Lyubchik, and R. Steingard (2002). We hypothesized that both parental depression and parenting quality mediate the effects of parental early adversity on offspring regulatory outcomes. Participants were 123 CWSI parents and their toddlers assessed three times over a period of 6 months. At Time 1, parents reported on their childhood adversity and current depressive symptoms. At Time 2, parents' sensitivity to their child's distress and nondistress cues was rated from a videotaped teaching task. At Time 3, observers rated children's emotional regulation, orientation/engagement, and secure base behavior. The results of a path model partly supported the hypotheses. Parent childhood adversity was associated with current depressive symptoms, which in turn related to parent sensitivity to child distress, but not nondistress. Sensitivity to distress also predicted secure base behavior. Depression directly predicted orientation/engagement, also predicted by sensitivity to nondistress. Sensitivity to distress predicted emotion regulation and orientation/engagement. Results are discussed in terms of intervention approaches for CWSI families. © 2017 Michigan Association for Infant Mental Health.

Predicting permanent and transient protein-protein interfaces.

PubMed

La, David; Kong, Misun; Hoffman, William; Choi, Youn Im; Kihara, Daisuke

2013-05-01

Protein-protein interactions (PPIs) are involved in diverse functions in a cell. To optimize functional roles of interactions, proteins interact with a spectrum of binding affinities. Interactions are conventionally classified into permanent and transient, where the former denotes tight binding between proteins that result in strong complexes, whereas the latter compose of relatively weak interactions that can dissociate after binding to regulate functional activity at specific time point. Knowing the type of interactions has significant implications for understanding the nature and function of PPIs. In this study, we constructed amino acid substitution models that capture mutation patterns at permanent and transient type of protein interfaces, which were found to be different with statistical significance. Using the substitution models, we developed a novel computational method that predicts permanent and transient protein binding interfaces (PBIs) in protein surfaces. Without knowledge of the interacting partner, the method uses a single query protein structure and a multiple sequence alignment of the sequence family. Using a large dataset of permanent and transient proteins, we show that our method, BindML+, performs very well in protein interface classification. A very high area under the curve (AUC) value of 0.957 was observed when predicted protein binding sites were classified. Remarkably, near prefect accuracy was achieved with an AUC of 0.991 when actual binding sites were classified. The developed method will be also useful for protein design of permanent and transient PBIs. Copyright © 2013 Wiley Periodicals, Inc.

Longitudinal Relationships Between Resources, Motivation, and Functioning

PubMed Central

Emery, Lisa; Neupert, Shevaun D.

2012-01-01

Objectives. We investigated how fluctuations and linear changes in health and cognitive resources influence the motivation to engage in complex cognitive activity and the extent to which motivation mediated the relationship between changing resources and cognitively demanding activities. Method. Longitudinal data from 332 adults aged 20–85 years were examined. Motivation was assessed using a composite of Need for Cognition and Personal Need for Structure and additional measures of health, sensory functioning, cognitive ability, and self-reported activity engagement. Results. Multilevel modeling revealed that age-typical changes in health, sensory functions, and ability were associated with changes in motivation, with the impact of declining health on motivation being particularly strong in older adulthood. Changes in motivation, in turn, predicted involvement in cognitive and social activities as well as changes in cognitive ability. Finally, motivation was observed to partially mediate the relationship between changes in resources and cognitively demanding activities. Discussion. Our results suggest that motivation may play an important role in determining the course of cognitive change and involvement in cognitively demanding everyday activities in adulthood. PMID:21926400

Sum rules across the unpolarized Compton processes involving generalized polarizabilities and moments of nucleon structure functions

NASA Astrophysics Data System (ADS)

Lensky, Vadim; Hagelstein, Franziska; Pascalutsa, Vladimir; Vanderhaeghen, Marc

2018-04-01

We derive two new sum rules for the unpolarized doubly virtual Compton scattering process on a nucleon, which establish novel low-Q2 relations involving the nucleon's generalized polarizabilities and moments of the nucleon's unpolarized structure functions F1(x ,Q2) and F2(x ,Q2). These relations facilitate the determination of some structure constants which can only be accessed in off-forward doubly virtual Compton scattering, not experimentally accessible at present. We perform an empirical determination for the proton and compare our results with a next-to-leading-order chiral perturbation theory prediction. We also show how these relations may be useful for a model-independent determination of the low-Q2 subtraction function in the Compton amplitude, which enters the two-photon-exchange contribution to the Lamb shift of (muonic) hydrogen. An explicit calculation of the Δ (1232 )-resonance contribution to the muonic-hydrogen 2 P -2 S Lamb shift yields -1 ±1 μ eV , confirming the previously conjectured smallness of this effect.

Language, music, syntax and the brain.

PubMed

Patel, Aniruddh D

2003-07-01

The comparative study of music and language is drawing an increasing amount of research interest. Like language, music is a human universal involving perceptually discrete elements organized into hierarchically structured sequences. Music and language can thus serve as foils for each other in the study of brain mechanisms underlying complex sound processing, and comparative research can provide novel insights into the functional and neural architecture of both domains. This review focuses on syntax, using recent neuroimaging data and cognitive theory to propose a specific point of convergence between syntactic processing in language and music. This leads to testable predictions, including the prediction that that syntactic comprehension problems in Broca's aphasia are not selective to language but influence music perception as well.

Energy landscapes for machine learning

NASA Astrophysics Data System (ADS)

Ballard, Andrew J.; Das, Ritankar; Martiniani, Stefano; Mehta, Dhagash; Sagun, Levent; Stevenson, Jacob D.; Wales, David J.

Machine learning techniques are being increasingly used as flexible non-linear fitting and prediction tools in the physical sciences. Fitting functions that exhibit multiple solutions as local minima can be analysed in terms of the corresponding machine learning landscape. Methods to explore and visualise molecular potential energy landscapes can be applied to these machine learning landscapes to gain new insight into the solution space involved in training and the nature of the corresponding predictions. In particular, we can define quantities analogous to molecular structure, thermodynamics, and kinetics, and relate these emergent properties to the structure of the underlying landscape. This Perspective aims to describe these analogies with examples from recent applications, and suggest avenues for new interdisciplinary research.

Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets

NASA Astrophysics Data System (ADS)

Selwa, Edithe; Martiny, Virginie Y.; Iorga, Bogdan I.

2016-09-01

The D3R Grand Challenge 2015 was focused on two protein targets: Heat Shock Protein 90 (HSP90) and Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4). We used a protocol involving a preliminary analysis of the available data in PDB and PubChem BioAssay, and then a docking/scoring step using more computationally demanding parameters that were required to provide more reliable predictions. We could evidence that different docking software and scoring functions can behave differently on individual ligand datasets, and that the flexibility of specific binding site residues is a crucial element to provide good predictions.

Location of skin lesions in Henoch-Schönlein purpura and its association with significant renal involvement.

PubMed

St John, Jessica; Vedak, Priyanka; Garza-Mayers, Anna Cristina; Hoang, Mai P; Nigwekar, Sagar U; Kroshinsky, Daniela

2018-01-01

Henoch-Schönlein purpura (HSP) is a small vessel IgA-predominant vasculitis. To describe adult patients with HSP and determine if the distribution of skin lesions (ie, purpura above the waist or purpura below the waist only), is a predictor of significant renal involvement at the time of the skin biopsy and the months following. A retrospective study on renal function from 72 adult patients with skin-biopsy proven HSP. Longitudinal renal data were analyzed after HSP diagnosis by using baseline renal function for comparison. Statistical analysis adjusted for sex, age, and baseline creatinine revealed a trend between HSP lesions only on the upper and lower extremities and long-term renal involvement (4.767, P = .067). Moreover, in another analysis adjusted for age and baseline creatinine, lesions located only on the upper and lower extremities significantly increased the odds of having long-term significant renal involvement (6.55, P = .049) in men. This retrospective study used patient information that was subject to selection bias. In patients with HSP, skin lesion distribution on the extremities might be predictive of significant long-term renal involvement and might be critical for risk stratification and development of personalized diagnostics and therapeutics. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

The impact of cognitive deficit on self-reported car crashes in ultra-octogenarian population: data of an Italian population-based study.

PubMed

Rozzini, Luca; Riva, Maddalena; Zanetti, Marina; Gottardi, Federica; Caratozzolo, Salvatore; Vicini Chilovi, Barbara; Trabucchi, Marco; Padovani, Alessandro

2013-06-01

To examine the usefulness of specific neurocognitive tests for predicting the crash involvement in ultra-octogenarian population. A total of 800 subjects (mean age 82.4 + 3.1 years) underwent a battery of neuropsychological tests. Global intellectual functioning was assessed using the Mini Mental State Examination, mental flexibility and information processing speed were assessed using the Trail Making Test parts A and B (TMT-A and TMT-B), long-term memory was evaluated with the short story, and visuo-spatial skills were tested with Clock Drawing Test. One year after this evaluation, 343 (43%) participants have been interviewed by a telephone call to know if they were currently driving and if they had a car crash during this period. Two hundred ninety-seven subjects had their driving license renewed and completed the follow-up 1 year after. Data shows that less than 11% of this group had a car crash during the first year of observation (Crash Involved). Older subjects involved in a car crash showed significant worse performances on TMT-B (TMT-B pathological Crash Involved vs. Noncrash Involved 47% vs. 27%; p = 0.02) and on short story (short story pathological Crash Involved vs. Noncrash Involved 19% vs. 5%; p = 0.02). Trail Making test B and short story have been demonstrated to provide a predictive value of driving performance of older people. Therefore, we suggest that a simple and standardized battery of neuropsychological tests, lasting about 30 min and administered by an experienced staff, is a good diagnostic instrument for risk prevention of driving activity of older drivers. Copyright © 2012 John Wiley & Sons, Ltd.

Use of Integrative Oncology, Involvement in Decision-Making, and Breast Cancer Survivor Health-Related Quality of Life in the First 5 Years Postdiagnosis.

PubMed

Andersen, M Robyn; Sweet, Erin; Hager, Shelly; Gaul, Marcia; Dowd, Fred; Standish, Leanna J

2018-03-01

This study sought to describe changes in the health-related quality of life (HRQOL) of women who do and do not seek naturopathic oncology (NO) complementary and alternative medicine (CAM) care during and immediately after breast cancer treatment, and to explore the predictive role of NO CAM care, demographic characteristics, and involvement in decision-making on HRQOL in breast cancer survivors. Matched cohorts of breast cancer survivors who did and did not choose to supplement their breast cancer treatment with NO care within 2 years of diagnosis participated. NO users were identified through naturopathic doctors' clinics and usual care (UC) controls with similar prognosis were identified through a cancer registry. The registry provided information about all participants' age, race, ethnicity, marital status, stage of cancer at time of diagnosis, date of diagnosis, and use of conventional medical treatments (surgery, chemotherapy, radiation, and endocrine therapy). Data of participants' self-reported involvement in decision-making and HRQOL were collected at study enrollment and at 6-month follow-up. At 6-month follow-up, the NO patients reported significantly more involvement in decision-making about care and better general health than did UC patients ( P < .05). Self-reported involvement in decision-making about cancer treatment was associated with better role-physical, role-emotional, and social-functional well-being ( P < .05). Race, age, marital status, and congruence of preferred and achieved levels of involvement also predicted aspects of HRQOL in breast cancer survivors ( P < .05). Both NO CAM care and involvement in decision-making about cancer treatment may be associated with better HRQOL in breast cancer survivors.

Attentive Motion Discrimination Recruits an Area in Inferotemporal Cortex

PubMed Central

Stemmann, Heiko

2016-01-01

Attentional selection requires the interplay of multiple brain areas. Theoretical accounts of selective attention predict different areas with different functional properties to support endogenous covert attention. To test these predictions, we devised a demanding attention task requiring motion discrimination and spatial selection and performed whole-brain imaging in macaque monkeys. Attention modulated the early visual cortex, motion-selective dorsal stream areas, the lateral intraparietal area, and the frontal eye fields. This pattern of activation supports early selection, feature-based, and biased-competition attention accounts, as well as the frontoparietal theory of attentional control. While high-level motion-selective dorsal stream areas did not exhibit strong attentional modulation, ventral stream areas V4d and the dorsal posterior inferotemporal cortex (PITd) did. The PITd in fact was, consistently across task variations, the most significantly and most strongly attention-modulated area, even though it did not exhibit signs of motion selectivity. Thus the recruitment of the PITd in attention tasks involving different kinds of motion analysis is not predicted by any theoretical account of attention. These functional data, together with known anatomical connections, suggest a general and possibly critical role of the PITd in attentional selection. SIGNIFICANCE STATEMENT Attention is the key cognitive function that selects sensory information relevant to the current goals, relegating other information to the shadows of consciousness. To better understand the neural mechanisms of this interplay between sensory processing and internal cognitive state, we must learn more about the brain areas supporting attentional selection. Here, to test theoretical accounts of attentional selection, we used a novel task requiring sustained attention to motion. We found that, surprisingly, among the most strongly attention-modulated areas is one that is neither selective for the sensory feature relevant for current goals nor one hitherto thought to be involved in attentional control. This discovery suggests a need for an extension of current theoretical accounts of the brain circuits for attentional selection. PMID:27881778

Comprehensive human transcription factor binding site map for combinatory binding motifs discovery.

PubMed

Müller-Molina, Arnoldo J; Schöler, Hans R; Araúzo-Bravo, Marcos J

2012-01-01

To know the map between transcription factors (TFs) and their binding sites is essential to reverse engineer the regulation process. Only about 10%-20% of the transcription factor binding motifs (TFBMs) have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory "DNA words." From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%-far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of "DNA words," newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters.

Comprehensive Human Transcription Factor Binding Site Map for Combinatory Binding Motifs Discovery

PubMed Central

Müller-Molina, Arnoldo J.; Schöler, Hans R.; Araúzo-Bravo, Marcos J.

2012-01-01

To know the map between transcription factors (TFs) and their binding sites is essential to reverse engineer the regulation process. Only about 10%–20% of the transcription factor binding motifs (TFBMs) have been reported. This lack of data hinders understanding gene regulation. To address this drawback, we propose a computational method that exploits never used TF properties to discover the missing TFBMs and their sites in all human gene promoters. The method starts by predicting a dictionary of regulatory “DNA words.” From this dictionary, it distills 4098 novel predictions. To disclose the crosstalk between motifs, an additional algorithm extracts TF combinatorial binding patterns creating a collection of TF regulatory syntactic rules. Using these rules, we narrowed down a list of 504 novel motifs that appear frequently in syntax patterns. We tested the predictions against 509 known motifs confirming that our system can reliably predict ab initio motifs with an accuracy of 81%—far higher than previous approaches. We found that on average, 90% of the discovered combinatorial binding patterns target at least 10 genes, suggesting that to control in an independent manner smaller gene sets, supplementary regulatory mechanisms are required. Additionally, we discovered that the new TFBMs and their combinatorial patterns convey biological meaning, targeting TFs and genes related to developmental functions. Thus, among all the possible available targets in the genome, the TFs tend to regulate other TFs and genes involved in developmental functions. We provide a comprehensive resource for regulation analysis that includes a dictionary of “DNA words,” newly predicted motifs and their corresponding combinatorial patterns. Combinatorial patterns are a useful filter to discover TFBMs that play a major role in orchestrating other factors and thus, are likely to lock/unlock cellular functional clusters. PMID:23209563

Inspiratory muscular weakness is most evident in chronic stroke survivors with lower walking speeds.

PubMed

Pinheiro, M B; Polese, J C; Faria, C D; Machado, G C; Parreira, V F; Britto, R R; Teixeira-Salmela, L F

2014-06-01

Respiratory muscular weakness and associated changes in thoracoabdominal motion have been poorly studied in stroke subjects, since the individuals' functional levels were not previously considered in the investigations. To investigate the breathing patterns, thoracoabdominal motion, and respiratory muscular strength in chronic stroke subjects, who were stratified into two groups, according to their walking speeds. Cross-sectional, observational study. University laboratory. Eighty-nine community-dwelling chronic stroke subjects The subjects, according to their gait speeds, were stratified into community (gait speed ≥0.8 m/s) and non-community ambulators (gait speed <0.8 m/s). Variables related to pulmonary function, breathing patterns, and thoracoabdominal motions were assessed. Measures of maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were obtained and were compared with the reference values for the Brazilian population. The MIP and MEP values were expressed as percentages of the predicted values. Mann-Whitney-U or independent Student t-tests were employed to compare the differences between the two groups for the selected variables. No significant between-group differences were found for the variables related to the breathing patterns and thoracoabdominal motions (0.01 < z/t < 1.51; 0.14

The Anterior Thalamus is Critical for Overcoming Interference in a Context-Dependent Odor Discrimination Task

PubMed Central

Law, L. Matthew; Smith, David M.

2012-01-01

The anterior thalamus (AT) is anatomically interconnected with the hippocampus and other structures known to be involved in memory, and the AT is involved in many of the same learning and memory functions as the hippocampus. For example, like the hippocampus, the AT is involved in spatial cognition and episodic memory. The hippocampus also has a well-documented role in contextual memory processes, but it is not known whether the AT is similarly involved in contextual memory. In the present study, we assessed the role of the AT in contextual memory processes by temporarily inactivating the AT and training rats on a recently developed context-based olfactory list learning task, which was designed to assess the use of contextual information to resolve interference. Rats were trained on one list of odor discrimination problems, followed by training on a second list in either the same context or a different context. In order to induce interference, some of the odors appeared on both lists with their predictive value reversed. Control rats that learned the two lists in different contexts performed significantly better than rats that learned the two lists in the same context. However, AT lesions completely abolished this contextual learning advantage, a result that is very similar to the effects of hippocampal inactivation. These findings demonstrate that the AT, like the hippocampus, is involved in contextual memory and suggest that the hippocampus and AT are part of a functional circuit involved in contextual memory. PMID:23025833

Benchmarking test of empirical root water uptake models

NASA Astrophysics Data System (ADS)

dos Santos, Marcos Alex; de Jong van Lier, Quirijn; van Dam, Jos C.; Freire Bezerra, Andre Herman

2017-01-01

Detailed physical models describing root water uptake (RWU) are an important tool for the prediction of RWU and crop transpiration, but the hydraulic parameters involved are hardly ever available, making them less attractive for many studies. Empirical models are more readily used because of their simplicity and the associated lower data requirements. The purpose of this study is to evaluate the capability of some empirical models to mimic the RWU distribution under varying environmental conditions predicted from numerical simulations with a detailed physical model. A review of some empirical models used as sub-models in ecohydrological models is presented, and alternative empirical RWU models are proposed. All these empirical models are analogous to the standard Feddes model, but differ in how RWU is partitioned over depth or how the transpiration reduction function is defined. The parameters of the empirical models are determined by inverse modelling of simulated depth-dependent RWU. The performance of the empirical models and their optimized empirical parameters depends on the scenario. The standard empirical Feddes model only performs well in scenarios with low root length density R, i.e. for scenarios with low RWU compensation. For medium and high R, the Feddes RWU model cannot mimic properly the root uptake dynamics as predicted by the physical model. The Jarvis RWU model in combination with the Feddes reduction function (JMf) only provides good predictions for low and medium R scenarios. For high R, it cannot mimic the uptake patterns predicted by the physical model. Incorporating a newly proposed reduction function into the Jarvis model improved RWU predictions. Regarding the ability of the models to predict plant transpiration, all models accounting for compensation show good performance. The Akaike information criterion (AIC) indicates that the Jarvis (2010) model (JMII), with no empirical parameters to be estimated, is the best model. The proposed models are better in predicting RWU patterns similar to the physical model. The statistical indices point to them as the best alternatives for mimicking RWU predictions of the physical model.

Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults

PubMed Central

Spreng, R. Nathan; Cassidy, Benjamin N; Darboh, Bri S; DuPre, Elizabeth; Lockrow, Amber W; Setton, Roni; Turner, Gary R

2017-01-01

Abstract Background Age-related brain changes leading to altered socioemotional functioning may increase vulnerability to financial exploitation. If confirmed, this would suggest a novel mechanism leading to heightened financial exploitation risk in older adults. Development of predictive neural markers could facilitate increased vigilance and prevention. In this preliminary study, we sought to identify structural and functional brain differences associated with financial exploitation in older adults. Methods Financially exploited older adults (n = 13, 7 female) and a matched cohort of older adults who had been exposed to, but avoided, a potentially exploitative situation (n = 13, 7 female) were evaluated. Using magnetic resonance imaging, we examined cortical thickness and resting state functional connectivity. Behavioral data were collected using standardized cognitive assessments, self-report measures of mood and social functioning. Results The exploited group showed cortical thinning in anterior insula and posterior superior temporal cortices, regions associated with processing affective and social information, respectively. Functional connectivity encompassing these regions, within default and salience networks, was reduced, while between network connectivity was increased. Self-reported anger and hostility was higher for the exploited group. Conclusions We observed financial exploitation associated with brain differences in regions involved in socioemotional functioning. These exploratory and preliminary findings suggest that alterations in brain regions implicated in socioemotional functioning may be a marker of financial exploitation risk. Large-scale, prospective studies are necessary to validate this neural mechanism, and develop predictive markers for use in clinical practice. PMID:28369260

Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach

PubMed Central

Niculescu, A B; Levey, D F; Phalen, P L; Le-Niculescu, H; Dainton, H D; Jain, N; Belanger, E; James, A; George, S; Weber, H; Graham, D L; Schweitzer, R; Ladd, T B; Learman, R; Niculescu, E M; Vanipenta, N P; Khan, F N; Mullen, J; Shankar, G; Cook, S; Humbert, C; Ballew, A; Yard, M; Gelbart, T; Shekhar, A; Schork, N J; Kurian, S M; Sandusky, G E; Salomon, D R

2015-01-01

Worldwide, one person dies every 40 seconds by suicide, a potentially preventable tragedy. A limiting step in our ability to intervene is the lack of objective, reliable predictors. We have previously provided proof of principle for the use of blood gene expression biomarkers to predict future hospitalizations due to suicidality, in male bipolar disorder participants. We now generalize the discovery, prioritization, validation, and testing of such markers across major psychiatric disorders (bipolar disorder, major depressive disorder, schizoaffective disorder, and schizophrenia) in male participants, to understand commonalities and differences. We used a powerful within-participant discovery approach to identify genes that change in expression between no suicidal ideation and high suicidal ideation states (n=37 participants out of a cohort of 217 psychiatric participants followed longitudinally). We then used a convergent functional genomics (CFG) approach with existing prior evidence in the field to prioritize the candidate biomarkers identified in the discovery step. Next, we validated the top biomarkers from the prioritization step for relevance to suicidal behavior, in a demographically matched cohort of suicide completers from the coroner's office (n=26). The biomarkers for suicidal ideation only are enriched for genes involved in neuronal connectivity and schizophrenia, the biomarkers also validated for suicidal behavior are enriched for genes involved in neuronal activity and mood. The 76 biomarkers that survived Bonferroni correction after validation for suicidal behavior map to biological pathways involved in immune and inflammatory response, mTOR signaling and growth factor regulation. mTOR signaling is necessary for the effects of the rapid-acting antidepressant agent ketamine, providing a novel biological rationale for its possible use in treating acute suicidality. Similarly, MAOB, a target of antidepressant inhibitors, was one of the increased biomarkers for suicidality. We also identified other potential therapeutic targets or biomarkers for drugs known to mitigate suicidality, such as omega-3 fatty acids, lithium and clozapine. Overall, 14% of the top candidate biomarkers also had evidence for involvement in psychological stress response, and 19% for involvement in programmed cell death/cellular suicide (apoptosis). It may be that in the face of adversity (stress), death mechanisms are turned on at a cellular (apoptosis) and organismal level. Finally, we tested the top increased and decreased biomarkers from the discovery for suicidal ideation (CADM1, CLIP4, DTNA, KIF2C), prioritization with CFG for prior evidence (SAT1, SKA2, SLC4A4), and validation for behavior in suicide completers (IL6, MBP, JUN, KLHDC3) steps in a completely independent test cohort of psychiatric participants for prediction of suicidal ideation (n=108), and in a future follow-up cohort of psychiatric participants (n=157) for prediction of psychiatric hospitalizations due to suicidality. The best individual biomarker across psychiatric diagnoses for predicting suicidal ideation was SLC4A4, with a receiver operating characteristic (ROC) area under the curve (AUC) of 72%. For bipolar disorder in particular, SLC4A4 predicted suicidal ideation with an AUC of 93%, and future hospitalizations with an AUC of 70%. SLC4A4 is involved in brain extracellular space pH regulation. Brain pH has been implicated in the pathophysiology of acute panic attacks. We also describe two new clinical information apps, one for affective state (simplified affective state scale, SASS) and one for suicide risk factors (Convergent Functional Information for Suicide, CFI-S), and how well they predict suicidal ideation across psychiatric diagnoses (AUC of 85% for SASS, AUC of 89% for CFI-S). We hypothesized a priori, based on our previous work, that the integration of the top biomarkers and the clinical information into a universal predictive measure (UP-Suicide) would show broad-spectrum predictive ability across psychiatric diagnoses. Indeed, the UP-Suicide was able to predict suicidal ideation across psychiatric diagnoses with an AUC of 92%. For bipolar disorder, it predicted suicidal ideation with an AUC of 98%, and future hospitalizations with an AUC of 94%. Of note, both types of tests we developed (blood biomarkers and clinical information apps) do not require asking the individual assessed if they have thoughts of suicide, as individuals who are truly suicidal often do not share that information with clinicians. We propose that the widespread use of such risk prediction tests as part of routine or targeted healthcare assessments will lead to early disease interception followed by preventive lifestyle modifications and proactive treatment. PMID:26283638

Function-driven discovery of disease genes in zebrafish using an integrated genomics big data resource.

PubMed

Shim, Hongseok; Kim, Ji Hyun; Kim, Chan Yeong; Hwang, Sohyun; Kim, Hyojin; Yang, Sunmo; Lee, Ji Eun; Lee, Insuk

2016-11-16

Whole exome sequencing (WES) accelerates disease gene discovery using rare genetic variants, but further statistical and functional evidence is required to avoid false-discovery. To complement variant-driven disease gene discovery, here we present function-driven disease gene discovery in zebrafish (Danio rerio), a promising human disease model owing to its high anatomical and genomic similarity to humans. To facilitate zebrafish-based function-driven disease gene discovery, we developed a genome-scale co-functional network of zebrafish genes, DanioNet (www.inetbio.org/danionet), which was constructed by Bayesian integration of genomics big data. Rigorous statistical assessment confirmed the high prediction capacity of DanioNet for a wide variety of human diseases. To demonstrate the feasibility of the function-driven disease gene discovery using DanioNet, we predicted genes for ciliopathies and performed experimental validation for eight candidate genes. We also validated the existence of heterozygous rare variants in the candidate genes of individuals with ciliopathies yet not in controls derived from the UK10K consortium, suggesting that these variants are potentially involved in enhancing the risk of ciliopathies. These results showed that an integrated genomics big data for a model animal of diseases can expand our opportunity for harnessing WES data in disease gene discovery. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

De novo RNA-seq and functional annotation of Ornithonyssus bacoti.

PubMed

Niu, DongLing; Wang, RuiLing; Zhao, YaE; Yang, Rui; Hu, Li

2018-06-01

Ornithonyssus bacoti (Hirst) (Acari: Macronyssidae) is a vector and reservoir of pathogens causing serious infectious diseases, such as epidemic hemorrhagic fever, endemic typhus, tularemia, and leptospirosis. Its genome and transcriptome data are lacking in public databases. In this study, total RNA was extracted from live O. bacoti to conduct RNA-seq, functional annotation, coding domain sequence (CDS) prediction and simple sequence repeats (SSRs) detection. The results showed that 65.8 million clean reads were generated and assembled into 72,185 unigenes, of which 49.4% were annotated by seven functional databases. 23,121 unigenes were annotated and assigned to 457 species by non-redundant protein sequence database. The BLAST top-two hit species were Metaseiulus occidentalis and Ixodes scapularis. The procedure detected 12,426 SSRs, of which tri- and di-nucleotides were the most abundant types and the representative motifs were AAT/ATT and AC/GT. 26,936 CDS were predicted with a mean length of 711 bp. 87 unigenes of 30 functional genes, which are usually involved in stress responses, drug resistance, movement, metabolism and allergy, were further identified by bioinformatics methods. The unigenes putatively encoding cytochrome P450 proteins were further analyzed phylogenetically. In conclusion, this study completed the RNA-seq and functional annotation of O. bacoti successfully, which provides reliable molecular data for its future studies of gene function and molecular markers.

Does the PFC model of analogy account for decision making, problem solving, reasoning, flexibility, adaptability, and even creativity?

PubMed

Barutta, Joaquin; Guex, Raphael; Ibáñez, Agustín

2010-06-01

Abstract From everyday cognition to scientific discovery, analogical processes play an important role: bringing connection, integration, and interrelation of information. Recently, a PFC model of analogy has been proposed to explain many cognitive processes and integrate general functional properties of PFC. We argue here that analogical processes do not suffice to explain the cognitive processes and functions of PFC. Moreover the model does not satisfactorily integrate specific explanatory mechanisms required for the different processes involved. Its relevance would be improved if fewer cognitive phenomena were considered and more specific predictions and explanations about those processes were stated.

Dynamics of inhomogeneous chiral condensates

NASA Astrophysics Data System (ADS)

Carlomagno, Juan Pablo; Krein, Gastão; Kroff, Daniel; Peixoto, Thiago

2018-01-01

We study the dynamics of the formation of inhomogeneous chirally broken phases in the final stages of a heavy-ion collision, with particular interest on the time scales involved in the formation process. The study is conducted within the framework of a Ginzburg-Landau time evolution, driven by a free energy functional motivated by the Nambu-Jona-Lasinio model. Expansion of the medium is modeled by one-dimensional Bjorken flow and its effect on the formation of inhomogeneous condensates is investigated. We also use a free energy functional from a nonlocal Nambu-Jona-Lasinio model which predicts metastable phases that lead to long-lived inhomogeneous condensates before reaching an equilibrium phase with homogeneous condensates.

Tolerence for work-induced heat stress in men wearing liquidcooled garments

NASA Technical Reports Server (NTRS)

Blockley, W. V.; Roth, H. P.

1971-01-01

An investigation of the heat tolerance in men unable to dispose of metabolic heat as fast as it is produced within the body is discussed. Examinations were made of (a) the effect of work rate (metabolic rate) on tolerance time when body heat storage rate is a fixed quantity, and (b) tolerance time as a function of metabolic rate when heat loss is terminated after a thermal quasi-equilibrium was attained under comfortable conditions of heat transfer. The nature of the physiological mechanisms involved in such heat stress situations, and the possibility of using prediction techniques to establish standard procedures in emergencies involving cooling system failures are also discussed.

Overview of research on Bombyx mori microRNA

PubMed Central

Wang, Xin; Tang, Shun-ming; Shen, Xing-jia

2014-01-01

Abstract MicroRNAs (miRNAs) constitute some of the most significant regulatory factors involved at the post-transcriptional level after gene expression, contributing to the modulation of a large number of physiological processes such as development, metabolism, and disease occurrence. This review comprehensively and retrospectively explores the literature investigating silkworm, Bombyx mori L. (Lepidoptera: Bombicidae), miRNAs published to date, including discovery, identification, expression profiling analysis, target gene prediction, and the functional analysis of both miRNAs and their targets. It may provide experimental considerations and approaches for future study of miRNAs and benefit elucidation of the mechanisms of miRNAs involved in silkworm developmental processes and intracellular activities of other unknown non-coding RNAs. PMID:25368077

Microarray analysis reveals key genes and pathways in Tetralogy of Fallot

PubMed Central

He, Yue-E; Qiu, Hui-Xian; Jiang, Jian-Bing; Wu, Rong-Zhou; Xiang, Ru-Lian; Zhang, Yuan-Hai

2017-01-01

The aim of the present study was to identify key genes that may be involved in the pathogenesis of Tetralogy of Fallot (TOF) using bioinformatics methods. The GSE26125 microarray dataset, which includes cardiovascular tissue samples derived from 16 children with TOF and five healthy age-matched control infants, was downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed between TOF and control samples to identify differentially expressed genes (DEGs) using Student's t-test, and the R/limma package, with a log2 fold-change of >2 and a false discovery rate of <0.01 set as thresholds. The biological functions of DEGs were analyzed using the ToppGene database. The ReactomeFIViz application was used to construct functional interaction (FI) networks, and the genes in each module were subjected to pathway enrichment analysis. The iRegulon plugin was used to identify transcription factors predicted to regulate the DEGs in the FI network, and the gene-transcription factor pairs were then visualized using Cytoscape software. A total of 878 DEGs were identified, including 848 upregulated genes and 30 downregulated genes. The gene FI network contained seven function modules, which were all comprised of upregulated genes. Genes enriched in Module 1 were enriched in the following three neurological disorder-associated signaling pathways: Parkinson's disease, Alzheimer's disease and Huntington's disease. Genes in Modules 0, 3 and 5 were dominantly enriched in pathways associated with ribosomes and protein translation. The Xbox binding protein 1 transcription factor was demonstrated to be involved in the regulation of genes encoding the subunits of cytoplasmic and mitochondrial ribosomes, as well as genes involved in neurodegenerative disorders. Therefore, dysfunction of genes involved in signaling pathways associated with neurodegenerative disorders, ribosome function and protein translation may contribute to the pathogenesis of TOF. PMID:28713939

Predicting protein functions from redundancies in large-scale protein interaction networks

NASA Technical Reports Server (NTRS)

Samanta, Manoj Pratim; Liang, Shoudan

2003-01-01

Interpreting data from large-scale protein interaction experiments has been a challenging task because of the widespread presence of random false positives. Here, we present a network-based statistical algorithm that overcomes this difficulty and allows us to derive functions of unannotated proteins from large-scale interaction data. Our algorithm uses the insight that if two proteins share significantly larger number of common interaction partners than random, they have close functional associations. Analysis of publicly available data from Saccharomyces cerevisiae reveals >2,800 reliable functional associations, 29% of which involve at least one unannotated protein. By further analyzing these associations, we derive tentative functions for 81 unannotated proteins with high certainty. Our method is not overly sensitive to the false positives present in the data. Even after adding 50% randomly generated interactions to the measured data set, we are able to recover almost all (approximately 89%) of the original associations.

Revealing the Strong Functional Association of adipor2 and cdh13 with adipoq: A Gene Network Study.

PubMed

Bag, Susmita; Anbarasu, Anand

2015-04-01

In the present study, we have analyzed functional gene interactions of adiponectin gene (adipoq). The key role of adipoq is in regulating energy homeostasis and it functions as a novel signaling molecule for adipose tissue. Modules of highly inter-connected genes in disease-specific adipoq network are derived by integrating gene function and protein interaction data. Among twenty genes in adipoq web, adipoq is effectively conjoined with two genes: Adiponectin receptor 2 (adipor2) and cadherin 13 (cdh13). The functional analysis is done via ontological briefing and candidate disease identification. We observed that the highly efficient-interlinked genes connected with adipoq are adipor2 and cdh13. Interestingly, the ontological aspect of adipor2 and cdh13 in the adipoq network reveal the fact that adipoq and adipor2 are involved mostly in glucose and lipid metabolic processes. The gene cdh13 indulge in cell adhesion process with adipoq and adipor2. Our computational gene web analysis also predicts potential candidate disease recognition, thus indicating the involvement of adipoq, adipor2, and cdh13 with not only with obesity but also with breast cancer, leukemia, renal cancer, lung cancer, and cervical cancer. The current study provides researchers a comprehensible layout of adipoq network, its functional strategies and candidate disease approach associated with adipoq network.

Plasmon modes of bilayer molybdenum disulfide: a density functional study

NASA Astrophysics Data System (ADS)

Torbatian, Z.; Asgari, R.

2017-11-01

We explore the collective electronic excitations of bilayer molybdenum disulfide (MoS2) using density functional theory together with random phase approximation. The many-body dielectric function and electron energy-loss spectra are calculated using an ab initio based model involving material-realistic physical properties. The electron energy-loss function of the bilayer MoS2 system is found to be sensitive to either electron or hole doping and this is due to the fact that the Kohn-Sham band dispersions are not symmetric for energies above and below the zero Fermi level. Three plasmon modes are predicted, a damped high-energy mode, one optical mode (in-phase mode) for which the plasmon dispersion exhibits \\sqrt q in the long wavelength limit originating from low-energy electron scattering and finally a highly damped acoustic mode (out-of-phase mode).

Core executive functions are associated with success in young elite soccer players.

PubMed

Vestberg, Torbjörn; Reinebo, Gustaf; Maurex, Liselotte; Ingvar, Martin; Petrovic, Predrag

2017-01-01

Physical capacity and coordination cannot alone predict success in team sports such as soccer. Instead, more focus has been directed towards the importance of cognitive abilities, and it has been suggested that executive functions (EF) are fundamentally important for success in soccer. However, executive functions are going through a steep development from adolescence to adulthood. Moreover, more complex EF involving manipulation of information (higher level EF) develop later than simple executive functions such as those linked to simple working memory capacity (Core EF). The link between EF and success in young soccer players is therefore not obvious. In the present study we investigated whether EF are associated with success in soccer in young elite soccer players. We performed tests measuring core EF (a demanding working memory task involving a variable n-back task; dWM) and higher level EF (Design Fluency test; DF). Color-Word Interference Test and Trail Making Test were performed on an exploratory level as they contain a linguistic element. The lower level EF test (dWM) was taken from CogStateSport computerized concussion testing and the higher level EF test (DF) was from Delis-Kaplan Executive Function System test battery (D-KEFS). In a group of young elite soccer players (n = 30; aged 12-19 years) we show that they perform better than the norm in both the dWM (+0.49 SD) and DF (+0.86 SD). Moreover, we could show that both dWM and DF correlate with the number of goals the players perform during the season. The effect was more prominent for dWM (r = 0.437) than for DF (r = 0.349), but strongest for a combined measurement (r = 0.550). The effect was still present when we controlled for intelligence, length and age in a partial correlation analysis. Thus, our study suggests that both core and higher level EF may predict success in soccer also in young players.

Core executive functions are associated with success in young elite soccer players

PubMed Central

Reinebo, Gustaf; Maurex, Liselotte; Ingvar, Martin; Petrovic, Predrag

2017-01-01

Physical capacity and coordination cannot alone predict success in team sports such as soccer. Instead, more focus has been directed towards the importance of cognitive abilities, and it has been suggested that executive functions (EF) are fundamentally important for success in soccer. However, executive functions are going through a steep development from adolescence to adulthood. Moreover, more complex EF involving manipulation of information (higher level EF) develop later than simple executive functions such as those linked to simple working memory capacity (Core EF). The link between EF and success in young soccer players is therefore not obvious. In the present study we investigated whether EF are associated with success in soccer in young elite soccer players. We performed tests measuring core EF (a demanding working memory task involving a variable n-back task; dWM) and higher level EF (Design Fluency test; DF). Color-Word Interference Test and Trail Making Test were performed on an exploratory level as they contain a linguistic element. The lower level EF test (dWM) was taken from CogStateSport computerized concussion testing and the higher level EF test (DF) was from Delis-Kaplan Executive Function System test battery (D-KEFS). In a group of young elite soccer players (n = 30; aged 12–19 years) we show that they perform better than the norm in both the dWM (+0.49 SD) and DF (+0.86 SD). Moreover, we could show that both dWM and DF correlate with the number of goals the players perform during the season. The effect was more prominent for dWM (r = 0.437) than for DF (r = 0.349), but strongest for a combined measurement (r = 0.550). The effect was still present when we controlled for intelligence, length and age in a partial correlation analysis. Thus, our study suggests that both core and higher level EF may predict success in soccer also in young players. PMID:28178738

Discovering functions of unannotated genes from a transcriptome survey of wild fungal isolates.

PubMed

Ellison, Christopher E; Kowbel, David; Glass, N Louise; Taylor, John W; Brem, Rachel B

2014-04-01

Most fungal genomes are poorly annotated, and many fungal traits of industrial and biomedical relevance are not well suited to classical genetic screens. Assigning genes to phenotypes on a genomic scale thus remains an urgent need in the field. We developed an approach to infer gene function from expression profiles of wild fungal isolates, and we applied our strategy to the filamentous fungus Neurospora crassa. Using transcriptome measurements in 70 strains from two well-defined clades of this microbe, we first identified 2,247 cases in which the expression of an unannotated gene rose and fell across N. crassa strains in parallel with the expression of well-characterized genes. We then used image analysis of hyphal morphologies, quantitative growth assays, and expression profiling to test the functions of four genes predicted from our population analyses. The results revealed two factors that influenced regulation of metabolism of nonpreferred carbon and nitrogen sources, a gene that governed hyphal architecture, and a gene that mediated amino acid starvation resistance. These findings validate the power of our population-transcriptomic approach for inference of novel gene function, and we suggest that this strategy will be of broad utility for genome-scale annotation in many fungal systems. IMPORTANCE Some fungal species cause deadly infections in humans or crop plants, and other fungi are workhorses of industrial chemistry, including the production of biofuels. Advances in medical and industrial mycology require an understanding of the genes that control fungal traits. We developed a method to infer functions of uncharacterized genes by observing correlated expression of their mRNAs with those of known genes across wild fungal isolates. We applied this strategy to a filamentous fungus and predicted functions for thousands of unknown genes. In four cases, we experimentally validated the predictions from our method, discovering novel genes involved in the metabolism of nutrient sources relevant for biofuel production, as well as colony morphology and starvation resistance. Our strategy is straightforward, inexpensive, and applicable for predicting gene function in many fungal species.

Effects of war exposure on Air Force personnel’s mental health, job burnout and other organizational related outcomes

PubMed Central

Vinokur, Amiram D.; Pierce, Penny F.; Lewandowski-Romps, Lisa; Hobfoll, Stevan E.; Galea, Sandro

2011-01-01

Longitudinal data from a stratified representative sample of U.S. Air Force personnel (N = 1009) deployed to the wars in Iraq, Afghanistan, and other locations were analyzed in this study. Using structural equation models, we examined the effects of war exposure on traumatic experiences, Post Traumatic Stress (PTS) symptoms, resource loss, and on subsequent functioning, perceived health, and on job and organizationally relevant outcomes. The job and organizational outcomes included job burnout, job involvement, job strain, job satisfaction, work-family conflict, organizational commitment, deployment readiness, and intention to reenlist. We found that deployment to the theater of the war increased risk of exposure to trauma, which in turn, predicted elevated PTS symptoms and resource loss. PTS symptoms predicted later loss of resources and deterioration in perceived health and functioning. In turn, resource loss predicted negative job and organizational outcomes. Exposure to trauma fully mediated the effects of deployment to the theater of war on PTS symptoms and resource loss and had additional significant indirect effects on several job and organizational relevant outcomes. For returning veterans, deployment to the theater of war, exposure to trauma, PTS symptoms, and resource loss represents a ‘cascading’ chain of events that over time results in a decline of health and functioning as well as in adverse job and organizationally relevant outcomes that may affect organizational effectiveness. PMID:21280941

A 3D quantitative comparison of trapezium and trapezoid relative articular and nonarticular surface areas in modern humans and great apes.

PubMed

Tocheri, M W; Razdan, A; Williams, R C; Marzke, M W

2005-11-01

The structure and functions of the modern human hand are critical components of what distinguishes Homo sapiens from the great apes (Gorilla, Pan, and Pongo). In this study, attention is focused on the trapezium and trapezoid, the two most lateral bones of the distal carpal row, in the four extant hominid genera, representing the first time they have been quantified and analyzed together as a morphological-functional complex. Our objective is to quantify the relative articular and nonarticular surface areas of these two bones and to test whether modern humans exhibit significant shape differences from the great apes, as predicted by previous qualitative analyses and the functional demands of differing manipulative and locomotor strategies. Modern humans were predicted to show larger relative first metacarpal and scaphoid surfaces on the trapezium because of the regular recruitment of the thumb during manipulative behaviors; alternatively, great apes were predicted to show larger relative second metacarpal and scaphoid surfaces on the trapezoid because of the functional demands on the hands during locomotor behaviors. Modern humans were also expected to exhibit larger relative mutual joint surfaces between the trapezoid and adjacent carpals than do the great apes because of assumed transverse loads generated by the functional demands of the modern human power grip. Using 3D bone models acquired through laser digitizing, the relative articular and nonarticular areas on each bone are quantified and compared. Multivariate analyses of these data clearly distinguish modern humans from the great apes. In total, the observed differences between modern humans and the great apes support morphological predictions based on the fact that this region of the human wrist is no longer involved in weight-bearing during locomotor behavior and is instead recruited solely for manipulative behaviors. The results provide the beginnings of a 3D comparative standard against which further extant and fossil primate wrist bones can be compared within the contexts of manipulative and locomotor behaviors.

Cell fate reprogramming by control of intracellular network dynamics

NASA Astrophysics Data System (ADS)

Zanudo, Jorge G. T.; Albert, Reka

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell's fate, such as disease therapeutics and stem cell reprogramming. Although the topic of controlling the dynamics of a system has a long history in control theory, most of this work is not directly applicable to intracellular networks. Here we present a network control method that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our control method takes advantage of certain function-dependent network components and their relation to steady states in order to identify control targets, which are guaranteed to drive any initial state to the target state with 100% effectiveness and need to be applied only transiently for the system to reach and stay in the desired state. We illustrate our method's potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. This work was supported by NSF Grant PHY 1205840.

Isolation and in silico analysis of a novel H+-pyrophosphatase gene orthologue from the halophytic grass Leptochloa fusca

NASA Astrophysics Data System (ADS)

Rauf, Muhammad; Saeed, Nasir A.; Habib, Imran; Ahmed, Moddassir; Shahzad, Khurram; Mansoor, Shahid; Ali, Rashid

2017-02-01

Structure prediction can provide information about function and active sites of protein which helps to design new functional proteins. H+-pyrophosphatase is transmembrane protein involved in establishing proton motive force for active transport of Na+ across membrane by Na+/H+ antiporters. A full length novel H+-pyrophosphatase gene was isolated from halophytic grass Leptochloa fusca using RT-PCR and RACE method. Full length LfVP1 gene sequence of 2292 nucleotides encodes protein of 764 amino acids. DNA and protein sequences were used for characterization using bioinformatics tools. Various important potential sites were predicted by PROSITE webserver. Primary structural analysis showed LfVP1 as stable protein and Grand average hydropathy (GRAVY) indicated that LfVP1 protein has good hydrosolubility. Secondary structure analysis showed that LfVP1 protein sequence contains significant proportion of alpha helix and random coil. Protein membrane topology suggested the presence of 14 transmembrane domains and presence of catalytic domain in TM3. Three dimensional structure from LfVP1 protein sequence also indicated the presence of 14 transmembrane domains and hydrophobicity surface model showed amino acid hydrophobicity. Ramachandran plot showed that 98% amino acid residues were predicted in the favored region.

Computational prediction of protein interactions related to the invasion of erythrocytes by malarial parasites.

PubMed

Liu, Xuewu; Huang, Yuxiao; Liang, Jiao; Zhang, Shuai; Li, Yinghui; Wang, Jun; Shen, Yan; Xu, Zhikai; Zhao, Ya

2014-11-30

The invasion of red blood cells (RBCs) by malarial parasites is an essential step in the life cycle of Plasmodium falciparum. Human-parasite surface protein interactions play a critical role in this process. Although several interactions between human and parasite proteins have been discovered, the mechanism related to invasion remains poorly understood because numerous human-parasite protein interactions have not yet been identified. High-throughput screening experiments are not feasible for malarial parasites due to difficulty in expressing the parasite proteins. Here, we performed computational prediction of the PPIs involved in malaria parasite invasion to elucidate the mechanism by which invasion occurs. In this study, an expectation maximization algorithm was used to estimate the probabilities of domain-domain interactions (DDIs). Estimates of DDI probabilities were then used to infer PPI probabilities. We found that our prediction performance was better than that based on the information of D. melanogaster alone when information related to the six species was used. Prediction performance was assessed using protein interaction data from S. cerevisiae, indicating that the predicted results were reliable. We then used the estimates of DDI probabilities to infer interactions between 490 parasite and 3,787 human membrane proteins. A small-scale dataset was used to illustrate the usability of our method in predicting interactions between human and parasite proteins. The positive predictive value (PPV) was lower than that observed in S. cerevisiae. We integrated gene expression data to improve prediction accuracy and to reduce false positives. We identified 80 membrane proteins highly expressed in the schizont stage by fast Fourier transform method. Approximately 221 erythrocyte membrane proteins were identified using published mass spectral datasets. A network consisting of 205 interactions was predicted. Results of network analysis suggest that SNARE proteins of parasites and APP of humans may function in the invasion of RBCs by parasites. We predicted a small-scale PPI network that may be involved in parasite invasion of RBCs by integrating DDI information and expression profiles. Experimental studies should be conducted to validate the predicted interactions. The predicted PPIs help elucidate the mechanism of parasite invasion and provide directions for future experimental investigations.

Predicting New Materials for Hydrogen Storage Application

PubMed Central

Vajeeston, Ponniah; Ravindran, Ponniah; Fjellvåg, Helmer

2009-01-01

Knowledge about the ground-state crystal structure is a prerequisite for the rational understanding of solid-state properties of new materials. To act as an efficient energy carrier, hydrogen should be absorbed and desorbed in materials easily and in high quantities. Owing to the complexity in structural arrangements and difficulties involved in establishing hydrogen positions by x-ray diffraction methods, the structural information of hydrides are very limited compared to other classes of materials (like oxides, intermetallics, etc.). This can be overcome by conducting computational simulations combined with selected experimental study which can save environment, money, and man power. The predicting capability of first-principles density functional theory (DFT) is already well recognized and in many cases structural and thermodynamic properties of single/multi component system are predicted. This review will focus on possible new classes of materials those have high hydrogen content, demonstrate the ability of DFT to predict crystal structure, and search for potential meta-stable phases. Stabilization of such meta-stable phases is also discussed.

Experimental validation of a predicted feedback loop in the multi-oscillator clock of Arabidopsis thaliana

PubMed Central

Locke, James C W; Kozma-Bognár, László; Gould, Peter D; Fehér, Balázs; Kevei, Éva; Nagy, Ferenc; Turner, Matthew S; Hall, Anthony; Millar, Andrew J

2006-01-01

Our computational model of the circadian clock comprised the feedback loop between LATE ELONGATED HYPOCOTYL (LHY), CIRCADIAN CLOCK ASSOCIATED 1 (CCA1) and TIMING OF CAB EXPRESSION 1 (TOC1), and a predicted, interlocking feedback loop involving TOC1 and a hypothetical component Y. Experiments based on model predictions suggested GIGANTEA (GI) as a candidate for Y. We now extend the model to include a recently demonstrated feedback loop between the TOC1 homologues PSEUDO-RESPONSE REGULATOR 7 (PRR7), PRR9 and LHY and CCA1. This three-loop network explains the rhythmic phenotype of toc1 mutant alleles. Model predictions fit closely to new data on the gi;lhy;cca1 mutant, which confirm that GI is a major contributor to Y function. Analysis of the three-loop network suggests that the plant clock consists of morning and evening oscillators, coupled intracellularly, which may be analogous to coupled, morning and evening clock cells in Drosophila and the mouse. PMID:17102804

Predictive factors for the Nursing Diagnoses in people living with Acquired Immune Deficiency Syndrome 1

PubMed Central

da Silva, Richardson Augusto Rosendo; Costa, Romanniny Hévillyn Silva; Nelson, Ana Raquel Cortês; Duarte, Fernando Hiago da Silva; Prado, Nanete Caroline da Costa; Rodrigues, Eduardo Henrique Fagundes

2016-01-01

Abstract Objective: to identify the predictive factors for the nursing diagnoses in people living with Acquired Immune Deficiency Syndrome. Method: a cross-sectional study, undertaken with 113 people living with AIDS. The data were collected using an interview script and physical examination. Logistic regression was used for the data analysis, considering a level of significance of 10%. Results: the predictive factors identified were: for the nursing diagnosis of knowledge deficit-inadequate following of instructions and verbalization of the problem; for the nursing diagnosis of failure to adhere - years of study, behavior indicative of failure to adhere, participation in the treatment and forgetfulness; for the nursing diagnosis of sexual dysfunction - family income, reduced frequency of sexual practice, perceived deficit in sexual desire, perceived limitations imposed by the disease and altered body function. Conclusion: the predictive factors for these nursing diagnoses involved sociodemographic and clinical characteristics, defining characteristics, and related factors, which must be taken into consideration during the assistance provided by the nurse. PMID:27384466

Prediction of peer-rated adult hostility from autonomy struggles in adolescent–family interactions

PubMed Central

ALLEN, JOSEPH P.; HAUSER, STUART T.; O’CONNOR, THOMAS G.; BELL, KATHY L.

2006-01-01

Observed parent–adolescent autonomy struggles were assessed as potential predictors of the development of peer-rated hostility over a decade later in young adulthood in both normal and previously psychiatrically hospitalized groups of adolescents. Longitudinal, multireporter data were obtained by coding family interactions involving 83 adolescents and their parents at age 16 years and then obtaining ratings by close friends of adolescents’ hostility at age 25 years. Fathers’ behavior undermining adolescents’ autonomy in interactions at age 16 years were predictive of adolescents-as-young-adults’ hostility, as rated by close friends at age 25 years. These predictions contributed additional variance to understanding young adult hostility even after accounting for concurrent levels of adolescent hostility at age 16 years and paternal hostility at this age, each of which also significantly contributed to predicting future hostility. Results are discussed as highlighting a pathway by which difficulties attaining autonomy in adolescence may presage the development of long-term difficulties in social functioning. PMID:11893089

A Validation Summary of the NCC Turbulent Reacting/non-reacting Spray Computations

NASA Technical Reports Server (NTRS)

Raju, M. S.; Liu, N.-S. (Technical Monitor)

2000-01-01

This pper provides a validation summary of the spray computations performed as a part of the NCC (National Combustion Code) development activity. NCC is being developed with the aim of advancing the current prediction tools used in the design of advanced technology combustors based on the multidimensional computational methods. The solution procedure combines the novelty of the application of the scalar Monte Carlo PDF (Probability Density Function) method to the modeling of turbulent spray flames with the ability to perform the computations on unstructured grids with parallel computing. The calculation procedure was applied to predict the flow properties of three different spray cases. One is a nonswirling unconfined reacting spray, the second is a nonswirling unconfined nonreacting spray, and the third is a confined swirl-stabilized spray flame. The comparisons involving both gas-phase and droplet velocities, droplet size distributions, and gas-phase temperatures show reasonable agreement with the available experimental data. The comparisons involve both the results obtained from the use of the Monte Carlo PDF method as well as those obtained from the conventional computational fluid dynamics (CFD) solution. Detailed comparisons in the case of a reacting nonswirling spray clearly highlight the importance of chemistry/turbulence interactions in the modeling of reacting sprays. The results from the PDF and non-PDF methods were found to be markedly different and the PDF solution is closer to the reported experimental data. The PDF computations predict that most of the combustion occurs in a predominantly diffusion-flame environment. However, the non-PDF solution predicts incorrectly that the combustion occurs in a predominantly vaporization-controlled regime. The Monte Carlo temperature distribution shows that the functional form of the PDF for the temperature fluctuations varies substantially from point to point. The results also bring to the fore some of the deficiencies associated with the use of assumed-shape PDF methods in spray computations.

Gas Diffusion in Fluids Containing Bubbles

NASA Technical Reports Server (NTRS)

Zak, M.; Weinberg, M. C.

1982-01-01

Mathematical model describes movement of gases in fluid containing many bubbles. Model makes it possible to predict growth and shrink age of bubbles as function of time. New model overcomes complexities involved in analysis of varying conditions by making two simplifying assumptions. It treats bubbles as point sources, and it employs approximate expression for gas concentration gradient at liquid/bubble interface. In particular, it is expected to help in developing processes for production of high-quality optical glasses in space.

Neural mechanisms underlying spatial realignment during adaptation to optical wedge prisms.

PubMed

Chapman, Heidi L; Eramudugolla, Ranmalee; Gavrilescu, Maria; Strudwick, Mark W; Loftus, Andrea; Cunnington, Ross; Mattingley, Jason B

2010-07-01

Visuomotor adaptation to a shift in visual input produced by prismatic lenses is an example of dynamic sensory-motor plasticity within the brain. Prism adaptation is readily induced in healthy individuals, and is thought to reflect the brain's ability to compensate for drifts in spatial calibration between different sensory systems. The neural correlate of this form of functional plasticity is largely unknown, although current models predict the involvement of parieto-cerebellar circuits. Recent studies that have employed event-related functional magnetic resonance imaging (fMRI) to identify brain regions associated with prism adaptation have discovered patterns of parietal and cerebellar modulation as participants corrected their visuomotor errors during the early part of adaptation. However, the role of these regions in the later stage of adaptation, when 'spatial realignment' or true adaptation is predicted to occur, remains unclear. Here, we used fMRI to quantify the distinctive patterns of parieto-cerebellar activity as visuomotor adaptation develops. We directly contrasted activation patterns during the initial error correction phase of visuomotor adaptation with that during the later spatial realignment phase, and found significant recruitment of the parieto-cerebellar network--with activations in the right inferior parietal lobe and the right posterior cerebellum. These findings provide the first evidence of both cerebellar and parietal involvement during the spatial realignment phase of prism adaptation. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

A Computational Approach From Gene to Structure Analysis of the Human ABCA4 Transporter Involved in Genetic Retinal Diseases.

PubMed

Trezza, Alfonso; Bernini, Andrea; Langella, Andrea; Ascher, David B; Pires, Douglas E V; Sodi, Andrea; Passerini, Ilaria; Pelo, Elisabetta; Rizzo, Stanislao; Niccolai, Neri; Spiga, Ottavia

2017-10-01

The aim of this article is to report the investigation of the structural features of ABCA4, a protein associated with a genetic retinal disease. A new database collecting knowledge of ABCA4 structure may facilitate predictions about the possible functional consequences of gene mutations observed in clinical practice. In order to correlate structural and functional effects of the observed mutations, the structure of mouse P-glycoprotein was used as a template for homology modeling. The obtained structural information and genetic data are the basis of our relational database (ABCA4Database). Sequence variability among all ABCA4-deposited entries was calculated and reported as Shannon entropy score at the residue level. The three-dimensional model of ABCA4 structure was used to locate the spatial distribution of the observed variable regions. Our predictions from structural in silico tools were able to accurately link the functional effects of mutations to phenotype. The development of the ABCA4Database gathers all the available genetic and structural information, yielding a global view of the molecular basis of some retinal diseases. ABCA4 modeled structure provides a molecular basis on which to analyze protein sequence mutations related to genetic retinal disease in order to predict the risk of retinal disease across all possible ABCA4 mutations. Additionally, our ABCA4 predicted structure is a good starting point for the creation of a new data analysis model, appropriate for precision medicine, in order to develop a deeper knowledge network of the disease and to improve the management of patients.

Entertainment-education and recruitment of cornea donors: the role of emotion and issue involvement.

PubMed

Bae, Hyuhn-Suhck

2008-01-01

This study examined the role of emotional responses and viewer's level of issue involvement to an entertainment-education show about cornea donation in order to predict intention to register as cornea donors. Results confirmed that sympathy and empathy responses operated as a catalyst for issue involvement, which emerged as an important intermediary in the persuasion process. Issue involvement also was found to be a common causal antecedent of attitude, subjective norm, and perceived behavioral control, the last two of which predict intentions unlike attitude, which does not. The revised path model confirmed that involvement directly influences intention. The findings of this study suggest that adding emotion and involvement in the Theory of Planned Behavior (TPB) enhances the explanatory power of the theory in predicting intentions, which indicates the possibility of combining the Elaboration Likelihood Model (ELM) and the TPB in the prediction of human behaviors.

Predicting intensity ranks of peptide fragment ions.

PubMed

Frank, Ari M

2009-05-01

Accurate modeling of peptide fragmentation is necessary for the development of robust scoring functions for peptide-spectrum matches, which are the cornerstone of MS/MS-based identification algorithms. Unfortunately, peptide fragmentation is a complex process that can involve several competing chemical pathways, which makes it difficult to develop generative probabilistic models that describe it accurately. However, the vast amounts of MS/MS data being generated now make it possible to use data-driven machine learning methods to develop discriminative ranking-based models that predict the intensity ranks of a peptide's fragment ions. We use simple sequence-based features that get combined by a boosting algorithm into models that make peak rank predictions with high accuracy. In an accompanying manuscript, we demonstrate how these prediction models are used to significantly improve the performance of peptide identification algorithms. The models can also be useful in the design of optimal multiple reaction monitoring (MRM) transitions, in cases where there is insufficient experimental data to guide the peak selection process. The prediction algorithm can also be run independently through PepNovo+, which is available for download from http://bix.ucsd.edu/Software/PepNovo.html.

Predicting Intensity Ranks of Peptide Fragment Ions

PubMed Central

Frank, Ari M.

2009-01-01

Accurate modeling of peptide fragmentation is necessary for the development of robust scoring functions for peptide-spectrum matches, which are the cornerstone of MS/MS-based identification algorithms. Unfortunately, peptide fragmentation is a complex process that can involve several competing chemical pathways, which makes it difficult to develop generative probabilistic models that describe it accurately. However, the vast amounts of MS/MS data being generated now make it possible to use data-driven machine learning methods to develop discriminative ranking-based models that predict the intensity ranks of a peptide's fragment ions. We use simple sequence-based features that get combined by a boosting algorithm in to models that make peak rank predictions with high accuracy. In an accompanying manuscript, we demonstrate how these prediction models are used to significantly improve the performance of peptide identification algorithms. The models can also be useful in the design of optimal MRM transitions, in cases where there is insufficient experimental data to guide the peak selection process. The prediction algorithm can also be run independently through PepNovo+, which is available for download from http://bix.ucsd.edu/Software/PepNovo.html. PMID:19256476

How We Choose One over Another: Predicting Trial-by-Trial Preference Decision

PubMed Central

Bhushan, Vidya; Saha, Goutam; Lindsen, Job; Shimojo, Shinsuke; Bhattacharya, Joydeep

2012-01-01

Preference formation is a complex problem as it is subjective, involves emotion, is led by implicit processes, and changes depending on the context even within the same individual. Thus, scientific attempts to predict preference are challenging, yet quite important for basic understanding of human decision making mechanisms, but prediction in a group-average sense has only a limited significance. In this study, we predicted preferential decisions on a trial by trial basis based on brain responses occurring before the individuals made their decisions explicit. Participants made a binary preference decision of approachability based on faces while their electrophysiological responses were recorded. An artificial neural network based pattern-classifier was used with time-frequency resolved patterns of a functional connectivity measure as features for the classifier. We were able to predict preference decisions with a mean accuracy of 74.3±2.79% at participant-independent level and of 91.4±3.8% at participant-dependent level. Further, we revealed a causal role of the first impression on final decision and demonstrated the temporal trajectory of preference decision formation. PMID:22912859

CMPF: class-switching minimized pathfinding in metabolic networks.

PubMed

Lim, Kevin; Wong, Limsoon

2012-01-01

The metabolic network is an aggregation of enzyme catalyzed reactions that converts one compound to another. Paths in a metabolic network are a sequence of enzymes that describe how a chemical compound of interest can be produced in a biological system. As the number of such paths is quite large, many methods have been developed to score paths so that the k-shortest paths represent the set of paths that are biologically meaningful or efficient. However, these approaches do not consider whether the sequence of enzymes can be manufactured in the same pathway/species/localization. As a result, a predicted sequence might consist of groups of enzymes that operate in distinct pathway/species/localization and may not truly reflect the events occurring within cell. We propose a path weighting method CMPF (Class-switching Minimized Pathfinder) to search for routes in a metabolic network which minimizes pathway switching. In biological terms, a pathway is a series of chemical reactions which define a specific function (e.g. glycolysis). We conjecture that routes that cross many pathways are inefficient since different pathways define different metabolic functions. In addition, native routes are also well characterized within pathways, suggesting that reasonable paths should not involve too many pathway switches. Our method can be generalized when reactions participate in a class set (e.g., pathways, species or cellular localization) so that the paths predicted have minimal class crossings. We show that our method generates k-paths that involve the least number of class switching. In addition, we also show that native paths are recoverable and alternative paths deviates less from native paths compared to other methods. This suggests that paths ranked by our method could be a way to predict paths that are likely to occur in biological systems.

An Analytical Model for Two-Order Asperity Degradation of Rock Joints Under Constant Normal Stiffness Conditions

NASA Astrophysics Data System (ADS)

Li, Yingchun; Wu, Wei; Li, Bo

2018-05-01

Jointed rock masses during underground excavation are commonly located under the constant normal stiffness (CNS) condition. This paper presents an analytical formulation to predict the shear behaviour of rough rock joints under the CNS condition. The dilatancy and deterioration of two-order asperities are quantified by considering the variation of normal stress. We separately consider the dilation angles of waviness and unevenness, which decrease to zero as the normal stress approaches the transitional stress. The sinusoidal function naturally yields the decay of dilation angle as a function of relative normal stress. We assume that the magnitude of transitional stress is proportionate to the square root of asperity geometric area. The comparison between the analytical prediction and experimental data shows the reliability of the analytical model. All the parameters involved in the analytical model possess explicit physical meanings and are measurable from laboratory tests. The proposed model is potentially practicable for assessing the stability of underground structures at various field scales.

The value of identity: olfactory notes on orbitofrontal cortex function.

PubMed

Gottfried, Jay A; Zelano, Christina

2011-12-01

Neuroscientific research has emphatically promoted the idea that the key function of the orbitofrontal cortex (OFC) is to encode value. Associative learning studies indicate that OFC representations of stimulus cues reflect the predictive value of expected outcomes. Neuroeconomic studies suggest that the OFC distills abstract representations of value from discrete commodities to optimize choice. Although value-based models provide good explanatory power for many different findings, these models are typically disconnected from the very stimuli and commodities giving rise to those value representations. Little provision is made, either theoretically or empirically, for the necessary cooperative role of object identity, without which value becomes orphaned from its source. As a step toward remediating the value of identity, this review provides a focused olfactory survey of OFC research, including new work from our lab, to highlight the elemental involvement of this region in stimulus-specific predictive coding of both perceptual outcomes and expected values. © 2011 New York Academy of Sciences.

A bottom-up characterization of transfer functions for synthetic biology designs: lessons from enzymology

PubMed Central

Carbonell-Ballestero, Max; Duran-Nebreda, Salva; Montañez, Raúl; Solé, Ricard; Macía, Javier; Rodríguez-Caso, Carlos

2014-01-01

Within the field of synthetic biology, a rational design of genetic parts should include a causal understanding of their input-output responses—the so-called transfer function—and how to tune them. However, a commonly adopted strategy is to fit data to Hill-shaped curves without considering the underlying molecular mechanisms. Here we provide a novel mathematical formalization that allows prediction of the global behavior of a synthetic device by considering the actual information from the involved biological parts. This is achieved by adopting an enzymology-like framework, where transfer functions are described in terms of their input affinity constant and maximal response. As a proof of concept, we characterize a set of Lux homoserine-lactone-inducible genetic devices with different levels of Lux receptor and signal molecule. Our model fits the experimental results and predicts the impact of the receptor's ribosome-binding site strength, as a tunable parameter that affects gene expression. The evolutionary implications are outlined. PMID:25404136

Exploring protein kinase conformation using swarm-enhanced sampling molecular dynamics.

PubMed

Atzori, Alessio; Bruce, Neil J; Burusco, Kepa K; Wroblowski, Berthold; Bonnet, Pascal; Bryce, Richard A

2014-10-27

Protein plasticity, while often linked to biological function, also provides opportunities for rational design of selective and potent inhibitors of their function. The application of computational methods to the prediction of concealed protein concavities is challenging, as the motions involved can be significant and occur over long time scales. Here we introduce the swarm-enhanced sampling molecular dynamics (sesMD) method as a tool to improve sampling of conformational landscapes. In this approach, a swarm of replica simulations interact cooperatively via a set of pairwise potentials incorporating attractive and repulsive components. We apply the sesMD approach to explore the conformations of the DFG motif in the protein p38α mitogen-activated protein kinase. In contrast to multiple MD simulations, sesMD trajectories sample a range of DFG conformations, some of which map onto existing crystal structures. Simulated structures intermediate between the DFG-in and DFG-out conformations are predicted to have druggable pockets of interest for structure-based ligand design.

Prolonged Financial Distress After the Deepwater Horizon Oil Spill Predicts Behavioral Health.

PubMed

Buckingham-Howes, Stacy; Holmes, Katherine; Glenn Morris, J; Grattan, Lynn M

2018-03-13

The economic impact of disasters is well known; however, the link between financial loss and behavioral health problems is unknown. Participants included 198 adults of ages 21 to 82, living within 10 miles of the Gulf Coast during the Deepwater Horizon Oil Spill and were involved in the fishing, harvesting, seafood processing, or service/tourism industries. The functional impact of financial resource loss at 2.5 years post spill was measured using the 26-item Financial Life Events Checklist (FLEC). Individuals responded to financial distress by reducing social events and utility bills and changing food-shopping habits. The FLEC significantly predicted higher drug use (Drug Abuse Screening Test), alcohol use (Alcohol Use Disorders Identification Test), mood problems (Profile of Mood States), and depressive symptoms (Beck Depression Inventory II) (p values ≤ 0.05) 4.5 years after the spill. This preliminary study supports the notion that the functional impact of financial loss has a long-term impact on behavioral health after an oil spill.

Mesolimbic Dopamine Signals the Value of Work

PubMed Central

Hamid, Arif A.; Pettibone, Jeffrey R.; Mabrouk, Omar S.; Hetrick, Vaughn L.; Schmidt, Robert; Vander Weele, Caitlin M.; Kennedy, Robert T.; Aragona, Brandon J.; Berke, Joshua D.

2015-01-01

Dopamine cell firing can encode errors in reward prediction, providing a learning signal to guide future behavior. Yet dopamine is also a key modulator of motivation, invigorating current behavior. Existing theories propose that fast (“phasic”) dopamine fluctuations support learning, while much slower (“tonic”) dopamine changes are involved in motivation. We examined dopamine release in the nucleus accumbens across multiple time scales, using complementary microdialysis and voltammetric methods during adaptive decision-making. We first show that minute-by-minute dopamine levels covary with reward rate and motivational vigor. We then show that second-by-second dopamine release encodes an estimate of temporally-discounted future reward (a value function). We demonstrate that changing dopamine immediately alters willingness to work, and reinforces preceding action choices by encoding temporal-difference reward prediction errors. Our results indicate that dopamine conveys a single, rapidly-evolving decision variable, the available reward for investment of effort, that is employed for both learning and motivational functions. PMID:26595651

The role of domain-general cognitive resources in children's construction of a vitalist theory of biology.

PubMed

Bascandziev, Igor; Tardiff, Nathan; Zaitchik, Deborah; Carey, Susan

2018-08-01

Some episodes of learning are easier than others. Preschoolers can learn certain facts, such as "my grandmother gave me this purse," only after one or two exposures (easy to learn; fast mapping), but they require several years to learn that plants are alive or that the sun is not alive (hard to learn). One difference between the two kinds of knowledge acquisition is that hard cases often require conceptual construction, such as the construction of the biological concept alive, whereas easy cases merely involve forming new beliefs formulated over concepts the child already has (belief revision, a form of knowledge enrichment). We asked whether different domain-general cognitive resources support these two types of knowledge acquisition (conceptual construction and knowledge enrichment that supports fast mapping) by testing 82 6-year-olds in a pre-training/training/post-training study. We measured children's improvement in an episode involving theory construction (the beginning steps of acquisition of the framework theory of vitalist biology, which requires conceptual change) and in an episode involving knowledge enrichment alone (acquisition of little known facts about animals, such as the location of crickets' ears and the color of octopus blood). In addition, we measured children's executive functions and receptive vocabulary to directly compare the resources drawn upon in the two episodes of learning. We replicated and extended previous findings highlighting the differences between conceptual construction and knowledge enrichment, and we found that Executive Functions predict improvement on the Vitalism battery but not on the Fun Facts battery and that Receptive Vocabulary predicts improvement the Fun Facts battery but not on the Vitalism battery. This double dissociation provides new evidence for the distinction between the two types of knowledge acquisition, and bears on the nature of the learning mechanisms involved in each. Copyright © 2018 Elsevier Inc. All rights reserved.

Simulating the effects of fluctuating dissolved oxygen on growth, reproduction, and survival of fish and shrimp.

PubMed

Miller Neilan, Rachael; Rose, Kenneth

2014-02-21

Individuals are commonly exposed to fluctuating levels of stressors, while most laboratory experiments focus on constant exposures. We develop and test a mathematical model for predicting the effects of low dissolved oxygen (hypoxia) on growth, reproduction, and survival using laboratory experiments on fish and shrimp. The exposure-effects model simulates the hourly reductions in growth and survival, and the reduction in reproduction (fecundity) at times of spawning, of an individual as it is exposed to constant or hourly fluctuating dissolved oxygen (DO) concentrations. The model was applied to seven experiments involving fish and shrimp that included constant and fluctuating DO exposures, with constant exposures used for parameter estimation and the model then used to simulate the growth, reproduction, and survival in the fluctuating treatments. Cumulative effects on growth, reproduction, and survival were predicted well by the model, but the model did not replay the observed episodic low survival days. Further investigation should involve the role of acclimation, possible inclusion of repair effects in reproduction and survival, and the sensitivity of model predictions to the shape of the immediate effects function. Additional testing of the model with other taxa, different patterns of fluctuating exposures, and different stressors is needed to determine the model's generality and robustness. © 2013 Elsevier Ltd. All rights reserved.

Functional neuroanatomy of intuitive physical inference

PubMed Central

Mikhael, John G.; Tenenbaum, Joshua B.; Kanwisher, Nancy

2016-01-01

To engage with the world—to understand the scene in front of us, plan actions, and predict what will happen next—we must have an intuitive grasp of the world’s physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events—a “physics engine” in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general “multiple demand” system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action. PMID:27503892

Functional neuroanatomy of intuitive physical inference.

PubMed

Fischer, Jason; Mikhael, John G; Tenenbaum, Joshua B; Kanwisher, Nancy

2016-08-23

To engage with the world-to understand the scene in front of us, plan actions, and predict what will happen next-we must have an intuitive grasp of the world's physical structure and dynamics. How do the objects in front of us rest on and support each other, how much force would be required to move them, and how will they behave when they fall, roll, or collide? Despite the centrality of physical inferences in daily life, little is known about the brain mechanisms recruited to interpret the physical structure of a scene and predict how physical events will unfold. Here, in a series of fMRI experiments, we identified a set of cortical regions that are selectively engaged when people watch and predict the unfolding of physical events-a "physics engine" in the brain. These brain regions are selective to physical inferences relative to nonphysical but otherwise highly similar scenes and tasks. However, these regions are not exclusively engaged in physical inferences per se or, indeed, even in scene understanding; they overlap with the domain-general "multiple demand" system, especially the parts of that system involved in action planning and tool use, pointing to a close relationship between the cognitive and neural mechanisms involved in parsing the physical content of a scene and preparing an appropriate action.

Ecological transition predictably associated with gene degeneration.

PubMed

Wessinger, Carolyn A; Rausher, Mark D

2015-02-01

Gene degeneration or loss can significantly contribute to phenotypic diversification, but may generate genetic constraints on future evolutionary trajectories, potentially restricting phenotypic reversal. Such constraints may manifest as directional evolutionary trends when parallel phenotypic shifts consistently involve gene degeneration or loss. Here, we demonstrate that widespread parallel evolution in Penstemon from blue to red flowers predictably involves the functional inactivation and degeneration of the enzyme flavonoid 3',5'-hydroxylase (F3'5'H), an anthocyanin pathway enzyme required for the production of blue floral pigments. Other types of genetic mutations do not consistently accompany this phenotypic shift. This pattern may be driven by the relatively large mutational target size of degenerative mutations to this locus and the apparent lack of associated pleiotropic effects. The consistent degeneration of F3'5'H may provide a mechanistic explanation for the observed asymmetry in the direction of flower color evolution in Penstemon: Blue to red transitions are common, but reverse transitions have not been observed. Although phenotypic shifts in this system are likely driven by natural selection, internal constraints may generate predictable genetic outcomes and may restrict future evolutionary trajectories. © The Author 2014. 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.

Assessing the Driver’s Current Level of Working Memory Load with High Density Functional Near-infrared Spectroscopy: A Realistic Driving Simulator Study

PubMed Central

Unni, Anirudh; Ihme, Klas; Jipp, Meike; Rieger, Jochem W.

2017-01-01

Cognitive overload or underload results in a decrease in human performance which may result in fatal incidents while driving. We envision that driver assistive systems which adapt their functionality to the driver’s cognitive state could be a promising approach to reduce road accidents due to human errors. This research attempts to predict variations of cognitive working memory load levels in a natural driving scenario with multiple parallel tasks and to reveal predictive brain areas. We used a modified version of the n-back task to induce five different working memory load levels (from 0-back up to 4-back) forcing the participants to continuously update, memorize, and recall the previous ‘n’ speed sequences and adjust their speed accordingly while they drove for approximately 60 min on a highway with concurrent traffic in a virtual reality driving simulator. We measured brain activation using multichannel whole head, high density functional near-infrared spectroscopy (fNIRS) and predicted working memory load level from the fNIRS data by combining multivariate lasso regression and cross-validation. This allowed us to predict variations in working memory load in a continuous time-resolved manner with mean Pearson correlations between induced and predicted working memory load over 15 participants of 0.61 [standard error (SE) 0.04] and a maximum of 0.8. Restricting the analysis to prefrontal sensors placed over the forehead reduced the mean correlation to 0.38 (SE 0.04), indicating additional information gained through whole head coverage. Moreover, working memory load predictions derived from peripheral heart rate parameters achieved much lower correlations (mean 0.21, SE 0.1). Importantly, whole head fNIRS sampling revealed increasing brain activation in bilateral inferior frontal and bilateral temporo-occipital brain areas with increasing working memory load levels suggesting that these areas are specifically involved in workload-related processing. PMID:28424602

Assessing the Driver's Current Level of Working Memory Load with High Density Functional Near-infrared Spectroscopy: A Realistic Driving Simulator Study.

PubMed

Unni, Anirudh; Ihme, Klas; Jipp, Meike; Rieger, Jochem W

2017-01-01

Cognitive overload or underload results in a decrease in human performance which may result in fatal incidents while driving. We envision that driver assistive systems which adapt their functionality to the driver's cognitive state could be a promising approach to reduce road accidents due to human errors. This research attempts to predict variations of cognitive working memory load levels in a natural driving scenario with multiple parallel tasks and to reveal predictive brain areas. We used a modified version of the n-back task to induce five different working memory load levels (from 0-back up to 4-back) forcing the participants to continuously update, memorize, and recall the previous 'n' speed sequences and adjust their speed accordingly while they drove for approximately 60 min on a highway with concurrent traffic in a virtual reality driving simulator. We measured brain activation using multichannel whole head, high density functional near-infrared spectroscopy (fNIRS) and predicted working memory load level from the fNIRS data by combining multivariate lasso regression and cross-validation. This allowed us to predict variations in working memory load in a continuous time-resolved manner with mean Pearson correlations between induced and predicted working memory load over 15 participants of 0.61 [standard error (SE) 0.04] and a maximum of 0.8. Restricting the analysis to prefrontal sensors placed over the forehead reduced the mean correlation to 0.38 (SE 0.04), indicating additional information gained through whole head coverage. Moreover, working memory load predictions derived from peripheral heart rate parameters achieved much lower correlations (mean 0.21, SE 0.1). Importantly, whole head fNIRS sampling revealed increasing brain activation in bilateral inferior frontal and bilateral temporo-occipital brain areas with increasing working memory load levels suggesting that these areas are specifically involved in workload-related processing.

Cell Fate Reprogramming by Control of Intracellular Network Dynamics

PubMed Central

Zañudo, Jorge G. T.; Albert, Réka

2015-01-01

Identifying control strategies for biological networks is paramount for practical applications that involve reprogramming a cell’s fate, such as disease therapeutics and stem cell reprogramming. Here we develop a novel network control framework that integrates the structural and functional information available for intracellular networks to predict control targets. Formulated in a logical dynamic scheme, our approach drives any initial state to the target state with 100% effectiveness and needs to be applied only transiently for the network to reach and stay in the desired state. We illustrate our method’s potential to find intervention targets for cancer treatment and cell differentiation by applying it to a leukemia signaling network and to the network controlling the differentiation of helper T cells. We find that the predicted control targets are effective in a broad dynamic framework. Moreover, several of the predicted interventions are supported by experiments. PMID:25849586

Anxiety, social skills, friendship quality, and peer victimization: an integrated model.

PubMed

Crawford, A Melissa; Manassis, Katharina

2011-10-01

This cross-sectional study investigated whether anxiety and social functioning interact in their prediction of peer victimization. A structural equation model linking anxiety, social skills, and friendship quality to victimization was tested separately for children with anxiety disorders and normal comparison children to explore whether the processes involved in victimization differ for these groups. Participants were 8-14 year old children: 55 (34 boys, 21 girls) diagnosed with an anxiety disorder and 85 (37 boys, 48 girls) normal comparison children. The final models for both groups yielded two independent pathways to victimization: (a) anxiety independently predicted being victimized; and (b) poor social skills predicted lower friendship quality, which in turn, placed a child at risk for victimization. These findings have important implications for the treatment of childhood anxiety disorders and for school-based anti-bullying interventions, but replication with larger samples is indicated. Copyright © 2011 Elsevier Ltd. All rights reserved.

Cooperative outcome interdependence, task reflexivity, and team effectiveness: a motivated information processing perspective.

PubMed

De Dreu, Carsten K W

2007-05-01

A motivated information processing perspective (C. K. W. De Dreu & P. J. D. Carnevale, 2003; see also V. B. Hinsz, R. S. Tindale, & D. A. Vollrath, 1997) was used to predict that perceived cooperative outcome interdependence interacts with team-level reflexivity to predict information sharing, learning, and team effectiveness. A cross-sectional field study involving management and cross-functional teams (N = 46) performing nonroutine, complex tasks corroborated predictions: The more team members perceived cooperative outcome interdependence, the better they shared information, the more they learned and the more effective they were, especially when task reflexivity was high. When task reflexivity was low, no significant relationship was found between cooperative outcome interdependence and team processes and performance. The author concludes that the motivated information processing perspective is valid outside the confines of the laboratory and can be extended toward teamwork in organizations. 2007 APA, all rights reserved

Rule Mining Techniques to Predict Prokaryotic Metabolic Pathways.

PubMed

Saidi, Rabie; Boudellioua, Imane; Martin, Maria J; Solovyev, Victor

2017-01-01

It is becoming more evident that computational methods are needed for the identification and the mapping of pathways in new genomes. We introduce an automatic annotation system (ARBA4Path Association Rule-Based Annotator for Pathways) that utilizes rule mining techniques to predict metabolic pathways across wide range of prokaryotes. It was demonstrated that specific combinations of protein domains (recorded in our rules) strongly determine pathways in which proteins are involved and thus provide information that let us very accurately assign pathway membership (with precision of 0.999 and recall of 0.966) to proteins of a given prokaryotic taxon. Our system can be used to enhance the quality of automatically generated annotations as well as annotating proteins with unknown function. The prediction models are represented in the form of human-readable rules, and they can be used effectively to add absent pathway information to many proteins in UniProtKB/TrEMBL database.

Household Socioeconomic Status and Parental Investments: Direct and Indirect Relations With School Readiness in Ghana.

PubMed

Wolf, Sharon; McCoy, Dana Charles

2017-07-14

This study examines how parent socioeconomic status (SES) directly and indirectly predicts children's school readiness through pathways of parental investment. Data come from direct assessments with preschool children and surveys with their primary caregivers in Ghana at the start of the 2015-2016 school year (N = 2,137; M age  = 5.2 years). Results revealed SES-related gaps in all parental investment characteristics and child school readiness skills. Preschool involvement served as the primary mediating mechanism in the path from SES to most school readiness skills, though it did not predict executive function. The number of books in the household was marginally positively predictive of early literacy, whereas at-home stimulation was negatively related to motor, literacy, and numeracy skills. © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

Towards agile large-scale predictive modelling in drug discovery with flow-based programming design principles.

PubMed

Lampa, Samuel; Alvarsson, Jonathan; Spjuth, Ola

2016-01-01

Predictive modelling in drug discovery is challenging to automate as it often contains multiple analysis steps and might involve cross-validation and parameter tuning that create complex dependencies between tasks. With large-scale data or when using computationally demanding modelling methods, e-infrastructures such as high-performance or cloud computing are required, adding to the existing challenges of fault-tolerant automation. Workflow management systems can aid in many of these challenges, but the currently available systems are lacking in the functionality needed to enable agile and flexible predictive modelling. We here present an approach inspired by elements of the flow-based programming paradigm, implemented as an extension of the Luigi system which we name SciLuigi. We also discuss the experiences from using the approach when modelling a large set of biochemical interactions using a shared computer cluster.Graphical abstract.

Structure and strategies in children's educational television: the roles of program type and learning strategies in children's learning.

PubMed

Linebarger, Deborah L; Piotrowski, Jessica Taylor

2010-01-01

Educational TV has been consistently linked to children's learning. In this research, educational TV characteristics were identified, coded, and tested for their influence on children's program-specific comprehension and vocabulary outcomes. Study 1 details a content analysis of TV features including a program's macrostructure (i.e., narrative or expository) and learning strategies embedded in the macrostructure that support learning in print-based contexts. In Study 2, regression analyses were used to predict outcomes involving 71 second and third graders (average age=7.63 years). Strategies were categorized as organizing, rehearsing, elaborating, or affective in function. Outcomes were uniformly higher for narrative macrostructures. Strategies used in narratives predicted relatively homogenous relations across outcomes, whereas strategies in expositories predicted quite heterogeneous relations across outcomes. © 2010 The Authors. Child Development © 2010 Society for Research in Child Development, Inc.

Sparse regressions for predicting and interpreting subcellular localization of multi-label proteins.

PubMed

Wan, Shibiao; Mak, Man-Wai; Kung, Sun-Yuan

2016-02-24

Predicting protein subcellular localization is indispensable for inferring protein functions. Recent studies have been focusing on predicting not only single-location proteins, but also multi-location proteins. Almost all of the high performing predictors proposed recently use gene ontology (GO) terms to construct feature vectors for classification. Despite their high performance, their prediction decisions are difficult to interpret because of the large number of GO terms involved. This paper proposes using sparse regressions to exploit GO information for both predicting and interpreting subcellular localization of single- and multi-location proteins. Specifically, we compared two multi-label sparse regression algorithms, namely multi-label LASSO (mLASSO) and multi-label elastic net (mEN), for large-scale predictions of protein subcellular localization. Both algorithms can yield sparse and interpretable solutions. By using the one-vs-rest strategy, mLASSO and mEN identified 87 and 429 out of more than 8,000 GO terms, respectively, which play essential roles in determining subcellular localization. More interestingly, many of the GO terms selected by mEN are from the biological process and molecular function categories, suggesting that the GO terms of these categories also play vital roles in the prediction. With these essential GO terms, not only where a protein locates can be decided, but also why it resides there can be revealed. Experimental results show that the output of both mEN and mLASSO are interpretable and they perform significantly better than existing state-of-the-art predictors. Moreover, mEN selects more features and performs better than mLASSO on a stringent human benchmark dataset. For readers' convenience, an online server called SpaPredictor for both mLASSO and mEN is available at http://bioinfo.eie.polyu.edu.hk/SpaPredictorServer/.

Targetome Analysis Revealed Involvement of MiR-126 in Neurotrophin Signaling Pathway: A Possible Role in Prevention of Glioma Development.

PubMed

Rouigari, Maedeh; Dehbashi, Moein; Ghaedi, Kamran; Pourhossein, Meraj

2018-07-01

For the first time, we used molecular signaling pathway enrichment analysis to determine possible involvement of miR-126 and IRS-1 in neurotrophin pathway. In this prospective study, Validated and predicted targets (targetome) of miR-126 were collected following searching miRtarbase (http://mirtarbase.mbc.nctu.edu.tw/) and miRWalk 2.0 databases, respectively. Then, approximate expression of miR-126 targeting in Glioma tissue was examined using UniGene database (http://www.ncbi. nlm.nih.gov/unigene). In silico molecular pathway enrichment analysis was carried out by DAVID 6.7 database (http://david. abcc.ncifcrf.gov/) to explore which signaling pathway is related to miR-126 targeting and how miR-126 attributes to glioma development. MiR-126 exerts a variety of functions in cancer pathogenesis via suppression of expression of target gene including PI3K, KRAS, EGFL7, IRS-1 and VEGF. Our bioinformatic studies implementing DAVID database, showed the involvement of miR-126 target genes in several signaling pathways including cancer pathogenesis, neurotrophin functions, Glioma formation, insulin function, focal adhesion production, chemokine synthesis and secretion and regulation of the actin cytoskeleton. Taken together, we concluded that miR-126 enhances the formation of glioma cancer stem cell probably via down regulation of IRS-1 in neurotrophin signaling pathway. Copyright© by Royan Institute. All rights reserved.

Transcriptome sequence analysis of an ornamental plant, Ananas comosus var. bracteatus, revealed the potential unigenes involved in terpenoid and phenylpropanoid biosynthesis.

PubMed

Ma, Jun; Kanakala, S; He, Yehua; Zhang, Junli; Zhong, Xiaolan

2015-01-01

Ananas comosus var. bracteatus (Red Pineapple) is an important ornamental plant for its colorful leaves and decorative red fruits. Because of its complex genome, it is difficult to understand the molecular mechanisms involved in the growth and development. Thus high-throughput transcriptome sequencing of Ananas comosus var. bracteatus is necessary to generate large quantities of transcript sequences for the purpose of gene discovery and functional genomic studies. The Ananas comosus var. bracteatus transcriptome was sequenced by the Illumina paired-end sequencing technology. We obtained a total of 23.5 million high quality sequencing reads, 1,555,808 contigs and 41,052 unigenes. In total 41,052 unigenes of Ananas comosus var. bracteatus, 23,275 unigenes were annotated in the NCBI non-redundant protein database and 23,134 unigenes were annotated in the Swiss-Port database. Out of these, 17,748 and 8,505 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. Functional annotation against Kyoto Encyclopedia of Genes and Genomes Pathway database identified 5,825 unigenes which were mapped to 117 pathways. The assembly predicted many unigenes that were previously unknown. The annotated unigenes were compared against pineapple, rice, maize, Arabidopsis, and sorghum. Unigenes that did not match any of those five sequence datasets are considered to be Ananas comosus var. bracteatus unique. We predicted unigenes encoding enzymes involved in terpenoid and phenylpropanoid biosynthesis. The sequence data provide the most comprehensive transcriptomic resource currently available for Ananas comosus var. bracteatus. To our knowledge; this is the first report on the de novo transcriptome sequencing of the Ananas comosus var. bracteatus. Unigenes obtained in this study, may help improve future gene expression, genetic and genomics studies in Ananas comosus var. bracteatus.

Transcriptome Sequence Analysis of an Ornamental Plant, Ananas comosus var. bracteatus, Revealed the Potential Unigenes Involved in Terpenoid and Phenylpropanoid Biosynthesis

PubMed Central

Ma, Jun; Kanakala, S.; He, Yehua; Zhang, Junli; Zhong, Xiaolan

2015-01-01

Background Ananas comosus var. bracteatus (Red Pineapple) is an important ornamental plant for its colorful leaves and decorative red fruits. Because of its complex genome, it is difficult to understand the molecular mechanisms involved in the growth and development. Thus high-throughput transcriptome sequencing of Ananas comosus var. bracteatus is necessary to generate large quantities of transcript sequences for the purpose of gene discovery and functional genomic studies. Results The Ananas comosus var. bracteatus transcriptome was sequenced by the Illumina paired-end sequencing technology. We obtained a total of 23.5 million high quality sequencing reads, 1,555,808 contigs and 41,052 unigenes. In total 41,052 unigenes of Ananas comosus var. bracteatus, 23,275 unigenes were annotated in the NCBI non-redundant protein database and 23,134 unigenes were annotated in the Swiss-Port database. Out of these, 17,748 and 8,505 unigenes were assigned to gene ontology categories and clusters of orthologous groups, respectively. Functional annotation against Kyoto Encyclopedia of Genes and Genomes Pathway database identified 5,825 unigenes which were mapped to 117 pathways. The assembly predicted many unigenes that were previously unknown. The annotated unigenes were compared against pineapple, rice, maize, Arabidopsis, and sorghum. Unigenes that did not match any of those five sequence datasets are considered to be Ananas comosus var. bracteatus unique. We predicted unigenes encoding enzymes involved in terpenoid and phenylpropanoid biosynthesis. Conclusion The sequence data provide the most comprehensive transcriptomic resource currently available for Ananas comosus var. bracteatus. To our knowledge; this is the first report on the de novo transcriptome sequencing of the Ananas comosus var. bracteatus. Unigenes obtained in this study, may help improve future gene expression, genetic and genomics studies in Ananas comosus var. bracteatus. PMID:25769053

Beyond an AFLP genome scan towards the identification of immune genes involved in plague resistance in Rattus rattus from Madagascar.

PubMed

Tollenaere, C; Jacquet, S; Ivanova, S; Loiseau, A; Duplantier, J-M; Streiff, R; Brouat, C

2013-01-01

Genome scans using amplified fragment length polymorphism (AFLP) markers became popular in nonmodel species within the last 10 years, but few studies have tried to characterize the anonymous outliers identified. This study follows on from an AFLP genome scan in the black rat (Rattus rattus), the reservoir of plague (Yersinia pestis infection) in Madagascar. We successfully sequenced 17 of the 22 markers previously shown to be potentially affected by plague-mediated selection and associated with a plague resistance phenotype. Searching these sequences in the genome of the closely related species Rattus norvegicus assigned them to 14 genomic regions, revealing a random distribution of outliers in the genome (no clustering). We compared these results with those of an in silico AFLP study of the R. norvegicus genome, which showed that outlier sequences could not have been inferred by this method in R. rattus (only four of the 15 sequences were predicted). However, in silico analysis allowed the prediction of AFLP markers distribution and the estimation of homoplasy rates, confirming its potential utility for designing AFLP studies in nonmodel species. The 14 genomic regions surrounding AFLP outliers (less than 300 kb from the marker) contained 75 genes encoding proteins of known function, including nine involved in immune function and pathogen defence. We identified the two interleukin 1 genes (Il1a and Il1b) that share homology with an antigen of Y. pestis, as the best candidates for genes subject to plague-mediated natural selection. At least six other genes known to be involved in proinflammatory pathways may also be affected by plague-mediated selection. © 2012 Blackwell Publishing Ltd.

Development and internal validation of a side-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer.

PubMed

Martini, Alberto; Gupta, Akriti; Lewis, Sara C; Cumarasamy, Shivaram; Haines, Kenneth G; Briganti, Alberto; Montorsi, Francesco; Tewari, Ashutosh K

2018-04-19

To develop a nomogram for predicting side-specific extracapsular extension (ECE) for planning nerve-sparing radical prostatectomy. We retrospectively analysed data from 561 patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015. To develop a side-specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate-specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side-specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using 'leave-one-out' cross-validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit. The study population consisted of 829 side-specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram-derived probability, using a 20% threshold for performing nerve-sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold. We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Knowledge-based prediction of protein backbone conformation using a structural alphabet.

PubMed

Vetrivel, Iyanar; Mahajan, Swapnil; Tyagi, Manoj; Hoffmann, Lionel; Sanejouand, Yves-Henri; Srinivasan, Narayanaswamy; de Brevern, Alexandre G; Cadet, Frédéric; Offmann, Bernard

2017-01-01

Libraries of structural prototypes that abstract protein local structures are known as structural alphabets and have proven to be very useful in various aspects of protein structure analyses and predictions. One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, PB-kPRED is proposed towards this aim. It involves (i) organizing the structural knowledge in the form of a database of pentapeptide fragments extracted from all protein structures in the PDB and (ii) applying a knowledge-based algorithm that does not rely on any secondary structure predictions and/or sequence alignment profiles, to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses the structural information from homologues in preference, if available. The predictions were evaluated rigorously on 15,544 query proteins representing a non-redundant subset of the PDB filtered at 30% sequence identity cut-off. We have shown that the kPRED method was able to achieve mean accuracies ranging from 40.8% to 66.3% depending on the availability of homologues. The impact of the different strategies for scanning the database on the prediction was evaluated and is discussed. Our results highlight the usefulness of the method in the context of proteins without any known structural homologues. A scoring function that gives a good estimate of the accuracy of prediction was further developed. This score estimates very well the accuracy of the algorithm (R2 of 0.82). An online version of the tool is provided freely for non-commercial usage at http://www.bo-protscience.fr/kpred/.

Analysis of the microRNA signature in left atrium from patients with valvular heart disease reveals their implications in atrial fibrillation.

PubMed

Doñate Puertas, Rosa; Jalabert, Audrey; Meugnier, Emmanuelle; Euthine, Vanessa; Chevalier, Philippe; Rome, Sophie

2018-01-01

Among the potential factors which may contribute to the development and perpetuation of atrial fibrillation, dysregulation of miRNAs has been suggested. Thus in this study, we have quantified the basal expressions of 662 mature human miRNAs in left atrium (LA) from patients undergoing cardiac surgery for valve repair, suffering or not from atrial fibrillation (AF) by using TaqMan® Low Density arrays (v2.0). Among the 299 miRNAs expressed in all patients, 42 miRNAs had altered basal expressions in patients with AF. Binding-site predictions with Targetscan (conserved sites among species) indicated that the up- and down-regulated miRNAs controlled respectively 3,310 and 5,868 genes. To identify the most relevant cellular functions under the control of the altered miRNAs, we focused on the 100 most targeted genes of each list and identified 5 functional protein-protein networks among these genes. Up-regulated networks were involved in synchronisation of circadian rythmicity and in the control of the AKT/PKC signaling pathway (i.e., proliferation/adhesion). Down-regulated networks were the IGF-1 pathway and TGF-beta signaling pathway and a network involved in RNA-mediated gene silencing, suggesting for the first time that alteration of miRNAs in AF would also perturbate the whole miRNA machinery. Then we crossed the list of miRNA predicted genes, and the list of mRNAs altered in similar patients suffering from AF and we found that respectively 44.5% and 55% of the up- and down-regulated mRNA are predicted to be conserved targets of the altered miRNAs (at least one binding site in 3'-UTR). As they were involved in the same biological processes mentioned above, these data demonstrated that a great part of the transcriptional defects previously published in LA from AF patients are likely due to defects at the post-transcriptional level and involved the miRNAs. Our stringent analysis permitted us to identify highly targeted protein-protein networks under the control of miRNAs in LA and, among them, to highlight those specifically affected in AF patients with altered miRNA signature. Further studies are now required to determine whether alterations of miRNA levels in AF pathology are causal or represent an adaptation to prevent cardiac electrical and structural remodeling.

Learning about learning: Mining human brain sub-network biomarkers from fMRI data

PubMed Central

Dereli, Nazli; Dang, Xuan-Hong; Bassett, Danielle S.; Wymbs, Nicholas F.; Grafton, Scott T.; Singh, Ambuj K.

2017-01-01

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in “resting state” employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions. PMID:29016686

Learning about learning: Mining human brain sub-network biomarkers from fMRI data.

PubMed

Bogdanov, Petko; Dereli, Nazli; Dang, Xuan-Hong; Bassett, Danielle S; Wymbs, Nicholas F; Grafton, Scott T; Singh, Ambuj K

2017-01-01

Modeling the brain as a functional network can reveal the relationship between distributed neurophysiological processes and functional interactions between brain structures. Existing literature on functional brain networks focuses mainly on a battery of network properties in "resting state" employing, for example, modularity, clustering, or path length among regions. In contrast, we seek to uncover functionally connected subnetworks that predict or correlate with cohort differences and are conserved within the subjects within a cohort. We focus on differences in both the rate of learning as well as overall performance in a sensorimotor task across subjects and develop a principled approach for the discovery of discriminative subgraphs of functional connectivity based on imaging acquired during practice. We discover two statistically significant subgraph regions: one involving multiple regions in the visual cortex and another involving the parietal operculum and planum temporale. High functional coherence in the former characterizes sessions in which subjects take longer to perform the task, while high coherence in the latter is associated with high learning rate (performance improvement across trials). Our proposed methodology is general, in that it can be applied to other cognitive tasks, to study learning or to differentiate between healthy patients and patients with neurological disorders, by revealing the salient interactions among brain regions associated with the observed global state. The discovery of such significant discriminative subgraphs promises a better data-driven understanding of the dynamic brain processes associated with high-level cognitive functions.

Acute Hepatopancreatic Necrosis Disease (AHPND) related microRNAs in Litopenaeus vannamei infected with AHPND-causing strain of Vibrio parahemolyticus.

PubMed

Zheng, Zhihong; Aweya, Jude Juventus; Wang, Fan; Yao, Defu; Lun, Jingsheng; Li, Shengkang; Ma, Hongyu; Zhang, Yueling

2018-05-08

Acute hepatopancreatic necrosis disease (AHPND) has emerged as a major debilitating disease that causes massive shrimp death resulting in substantial economic losses in shrimp aquaculture. Given that several diseases and infections have been associated with microRNAs (miRNAs), we conducted a comparative transcriptomic analysis using the AHPND (VA) and non-AHPND (VN) strains of Vibrio parahemolyticus to identify miRNAs potentially involved in AHPND pathogenesis in Litopenaeus vannamei. A total of 83 miRNAs (47 upregulated and 36 downregulated) were significantly differentially expressed between the VA and VN challenged groups, while 222 target genes of these miRNAs were predicted. Functional enrichment analysis revealed that the miRNAs target genes were involved in multiple biological processes including metabolic pathways, amoebiasis, Vibrio cholerae infection etc. Finally, interaction network and qPCR (Real-time Quantitative PCR) analysis of 12 potential key AHPND-related miRNAs and their predicted target genes, revealed their possible involvement in modulating several immune-related processes in the pathogenesis of AHPND. We have shown using comparative transcriptomic analysis, miRNAs and their target genes that are responsive to AHPND V. parahemolyticus infection in shrimp, therefore suggesting their possible role in defense response to AHPND V. parahemolyticus infection.

Shedding Some Light over the Floral Metabolism by Arum Lily (Zantedeschia aethiopica) Spathe De Novo Transcriptome Assembly

PubMed Central

Cândido, Elizabete de Souza; Fernandes, Gabriel da Rocha; de Alencar, Sérgio Amorim; Cardoso, Marlon Henrique e Silva; Lima, Stella Maris de Freitas; Miranda, Vívian de Jesus; Porto, William Farias; Nolasco, Diego Oliveira; de Oliveira-Júnior, Nelson Gomes; Barbosa, Aulus Estevão Anjos de Deus; Pogue, Robert Edward; Rezende, Taia Maria Berto; Dias, Simoni Campos; Franco, Octávio Luiz

2014-01-01

Zantedeschia aethiopica is an evergreen perennial plant cultivated worldwide and commonly used for ornamental and medicinal purposes including the treatment of bacterial infections. However, the current understanding of molecular and physiological mechanisms in this plant is limited, in comparison to other non-model plants. In order to improve understanding of the biology of this botanical species, RNA-Seq technology was used for transcriptome assembly and characterization. Following Z. aethiopica spathe tissue RNA extraction, high-throughput RNA sequencing was performed with the aim of obtaining both abundant and rare transcript data. Functional profiling based on KEGG Orthology (KO) analysis highlighted contigs that were involved predominantly in genetic information (37%) and metabolism (34%) processes. Predicted proteins involved in the plant circadian system, hormone signal transduction, secondary metabolism and basal immunity are described here. In silico screening of the transcriptome data set for antimicrobial peptide (AMP) –encoding sequences was also carried out and three lipid transfer proteins (LTP) were identified as potential AMPs involved in plant defense. Spathe predicted protein maps were drawn, and suggested that major plant efforts are expended in guaranteeing the maintenance of cell homeostasis, characterized by high investment in carbohydrate, amino acid and energy metabolism as well as in genetic information. PMID:24614014

The pgaABCD Locus of Escherichia coli Promotes the Synthesis of a Polysaccharide Adhesin Required for Biofilm Formation

PubMed Central

Wang, Xin; Preston, James F.; Romeo, Tony

2004-01-01

Production of a polysaccharide matrix is a hallmark of bacterial biofilms, but the composition of matrix polysaccharides and their functions are not widely understood. Previous studies of the regulation of Escherichia coli biofilm formation suggested the involvement of an unknown adhesin. We now establish that the pgaABCD (formerly ycdSRQP) locus affects biofilm development by promoting abiotic surface binding and intercellular adhesion. All of the pga genes are required for optimal biofilm formation under a variety of growth conditions. A pga-dependent cell-bound polysaccharide was isolated and determined by nuclear magnetic resonance analyses to consist of unbranched β-1,6-N-acetyl-d-glucosamine, a polymer previously unknown from the gram-negative bacteria but involved in adhesion by staphylococci. The pga genes are predicted to encode envelope proteins involved in synthesis, translocation, and possibly surface docking of this polysaccharide. As predicted, if poly-β-1,6-GlcNAc (PGA) mediates cohesion, metaperiodate caused biofilm dispersal and the release of intact cells, whereas treatment with protease or other lytic enzymes had no effect. The pgaABCD operon exhibits features of a horizontally transferred locus and is present in a variety of eubacteria. Therefore, we propose that PGA serves as an adhesin that stabilizes biofilms of E. coli and other bacteria. PMID:15090514

FDNS code to predict wall heat fluxes or wall temperatures in rocket nozzles

NASA Technical Reports Server (NTRS)

Karr, Gerald R.

1993-01-01

This report summarizes the findings on the NASA contract NAG8-212, Task No. 3. The overall project consists of three tasks, all of which have been successfully completed. In addition, some supporting supplemental work, not required by the contract, has been performed and is documented herein. Task 1 involved the modification of the wall functions in the code FDNS to use a Reynolds Analogy-based method. Task 2 involved the verification of the code against experimentally available data. The data chosen for comparison was from an experiment involving the injection of helium from a wall jet. Results obtained in completing this task also show the sensitivity of the FDNS code to unknown conditions at the injection slot. Task 3 required computation of the flow of hot exhaust gases through the P&W 40K subscale nozzle. Computations were performed both with and without film coolant injection. The FDNS program tends to overpredict heat fluxes, but, with suitable modeling of backside cooling, may give reasonable wall temperature predictions. For film cooling in the P&W 40K calorimeter subscale nozzle, the average wall temperature is reduced from 1750 R to about 1050 R by the film cooling. The average wall heat flux is reduced by a factor of three.

A CheR/CheB fusion protein is involved in cyst cell development and chemotaxis in Azospirillum brasilense Sp7.

PubMed

Wu, Lixian; Cui, Yanhua; Hong, Yuanyuan; Chen, Sanfeng

2011-12-20

We here report the sequence and functional analysis of cstB of Azospirillum brasilense Sp7. The predicted cstB contains C-terminal two PAS domains and N-terminal part which has similarity with CheB-CheR fusion protein. cstB mutants had reduced swarming ability compared to that of A. brasilense wild-type strain, implying that cstB was involved in chemotaxis in A. brasilense. A microscopic analysis revealed that cstB mutants developed mature cyst cells more quickly than wild type, indicating that cstB is involved in cyst formation. cstB mutants were affected in colony morphology and the production of exopolysaccharides (EPS) which are essential for A. brasilense cells to differentiate into cyst-like forms. These observations suggested that cstB was a multi-effector involved in cyst development and chemotaxis in A. brasilense. Copyright © 2010 Elsevier GmbH. All rights reserved.

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

PubMed

Gao, Qingsong; Liang, Wen-Wei; Foltz, Steven M; Mutharasu, Gnanavel; Jayasinghe, Reyka G; Cao, Song; Liao, Wen-Wei; Reynolds, Sheila M; Wyczalkowski, Matthew A; Yao, Lijun; Yu, Lihua; Sun, Sam Q; Chen, Ken; Lazar, Alexander J; Fields, Ryan C; Wendl, Michael C; Van Tine, Brian A; Vij, Ravi; Chen, Feng; Nykter, Matti; Shmulevich, Ilya; Ding, Li

2018-04-03

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of multiobjective evolutionary algorithms: empirical results.

PubMed

Zitzler, E; Deb, K; Thiele, L

2000-01-01

In this paper, we provide a systematic comparison of various evolutionary approaches to multiobjective optimization using six carefully chosen test functions. Each test function involves a particular feature that is known to cause difficulty in the evolutionary optimization process, mainly in converging to the Pareto-optimal front (e.g., multimodality and deception). By investigating these different problem features separately, it is possible to predict the kind of problems to which a certain technique is or is not well suited. However, in contrast to what was suspected beforehand, the experimental results indicate a hierarchy of the algorithms under consideration. Furthermore, the emerging effects are evidence that the suggested test functions provide sufficient complexity to compare multiobjective optimizers. Finally, elitism is shown to be an important factor for improving evolutionary multiobjective search.

Sodium sulfate - Deposition and dissolution of silica

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.

1989-01-01

The hot-corrosion process for SiO2-protected materials involves deposition of Na2SO4 and dissolution of the protective SiO2 scale. Dew points for Na2SO4 deposition are calculated as a function of pressure, sodium content, and sulfur content. Expected dissolution regimes for SiO2 are calculated as a function of Na2SO4 basicity. Controlled-condition burner-rig tests on quartz verify some of these predicted dissolution regimes. The basicity of Na2SO4 is not always a simple function of P(SO3). Electrochemical measurements of an (Na2O) show that carbon creates basic conditions in Na2SO4, which explains the extensive corrosion of SiO2-protected materials containing carbon, such as SiC.

Adsorption energies of benzene on close packed transition metal surfaces using the random phase approximation

NASA Astrophysics Data System (ADS)

Garrido Torres, José A.; Ramberger, Benjamin; Früchtl, Herbert A.; Schaub, Renald; Kresse, Georg

2017-11-01

The adsorption energy of benzene on various metal substrates is predicted using the random phase approximation (RPA) for the correlation energy. Agreement with available experimental data is systematically better than 10% for both coinage and reactive metals. The results are also compared with more approximate methods, including van der Waals density functional theory (DFT), as well as dispersion-corrected DFT functionals. Although dispersion-corrected DFT can yield accurate results, for instance, on coinage metals, the adsorption energies are clearly overestimated on more reactive transition metals. Furthermore, coverage dependent adsorption energies are well described by the RPA. This shows that for the description of aromatic molecules on metal surfaces further improvements in density functionals are necessary, or more involved many-body methods such as the RPA are required.

Mutation of the RDR1 gene caused genome-wide changes in gene expression, regional variation in small RNA clusters and localized alteration in DNA methylation in rice.

PubMed

Wang, Ningning; Zhang, Di; Wang, Zhenhui; Xun, Hongwei; Ma, Jian; Wang, Hui; Huang, Wei; Liu, Ying; Lin, Xiuyun; Li, Ning; Ou, Xiufang; Zhang, Chunyu; Wang, Ming-Bo; Liu, Bao

2014-06-30

Endogenous small (sm) RNAs (primarily si- and miRNAs) are important trans/cis-acting regulators involved in diverse cellular functions. In plants, the RNA-dependent RNA polymerases (RDRs) are essential for smRNA biogenesis. It has been established that RDR2 is involved in the 24 nt siRNA-dependent RNA-directed DNA methylation (RdDM) pathway. Recent studies have suggested that RDR1 is involved in a second RdDM pathway that relies mostly on 21 nt smRNAs and functions to silence a subset of genomic loci that are usually refractory to the normal RdDM pathway in Arabidopsis. Whether and to what extent the homologs of RDR1 may have similar functions in other plants remained unknown. We characterized a loss-of-function mutant (Osrdr1) of the OsRDR1 gene in rice (Oryza sativa L.) derived from a retrotransposon Tos17 insertion. Microarray analysis identified 1,175 differentially expressed genes (5.2% of all expressed genes in the shoot-tip tissue of rice) between Osrdr1 and WT, of which 896 and 279 genes were up- and down-regulated, respectively, in Osrdr1. smRNA sequencing revealed regional alterations in smRNA clusters across the rice genome. Some of the regions with altered smRNA clusters were associated with changes in DNA methylation. In addition, altered expression of several miRNAs was detected in Osrdr1, and at least some of which were associated with altered expression of predicted miRNA target genes. Despite these changes, no phenotypic difference was identified in Osrdr1 relative to WT under normal condition; however, ephemeral phenotypic fluctuations occurred under some abiotic stress conditions. Our results showed that OsRDR1 plays a role in regulating a substantial number of endogenous genes with diverse functions in rice through smRNA-mediated pathways involving DNA methylation, and which participates in abiotic stress response.

Dorsolateral prefrontal lesions do not impair tests of scene learning and decision-making that require frontal–temporal interaction

PubMed Central

Baxter, Mark G; Gaffan, David; Kyriazis, Diana A; Mitchell, Anna S

2008-01-01

Theories of dorsolateral prefrontal cortex (DLPFC) involvement in cognitive function variously emphasize its involvement in rule implementation, cognitive control, or working and/or spatial memory. These theories predict broad effects of DLPFC lesions on tests of visual learning and memory. We evaluated the effects of DLPFC lesions (including both banks of the principal sulcus) in rhesus monkeys on tests of scene learning and strategy implementation that are severely impaired following crossed unilateral lesions of frontal cortex and inferotemporal cortex. Dorsolateral lesions had no effect on learning of new scene problems postoperatively, or on the implementation of preoperatively acquired strategies. They were also without effect on the ability to adjust choice behaviour in response to a change in reinforcer value, a capacity that requires interaction between the amygdala and frontal lobe. These intact abilities following DLPFC damage support specialization of function within the prefrontal cortex, and suggest that many aspects of memory and strategic and goal-directed behaviour can survive ablation of this structure. PMID:18702721

Monitoring and control of amygdala neurofeedback involves distributed information processing in the human brain.

PubMed

Paret, Christian; Zähringer, Jenny; Ruf, Matthias; Gerchen, Martin Fungisai; Mall, Stephanie; Hendler, Talma; Schmahl, Christian; Ende, Gabriele

2018-03-30

Brain-computer interfaces provide conscious access to neural activity by means of brain-derived feedback ("neurofeedback"). An individual's abilities to monitor and control feedback are two necessary processes for effective neurofeedback therapy, yet their underlying functional neuroanatomy is still being debated. In this study, healthy subjects received visual feedback from their amygdala response to negative pictures. Activation and functional connectivity were analyzed to disentangle the role of brain regions in different processes. Feedback monitoring was mapped to the thalamus, ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and rostral PFC. The VS responded to feedback corresponding to instructions while rPFC activity differentiated between conditions and predicted amygdala regulation. Control involved the lateral PFC, anterior cingulate, and insula. Monitoring and control activity overlapped in the VS and thalamus. Extending current neural models of neurofeedback, this study introduces monitoring and control of feedback as anatomically dissociated processes, and suggests their important role in voluntary neuromodulation. © 2018 Wiley Periodicals, Inc.

Genomic and Coexpression Analyses Predict Multiple Genes Involved in Triterpene Saponin Biosynthesis in Medicago truncatula[C][W

PubMed Central

Naoumkina, Marina A.; Modolo, Luzia V.; Huhman, David V.; Urbanczyk-Wochniak, Ewa; Tang, Yuhong; Sumner, Lloyd W.; Dixon, Richard A.

2010-01-01

Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones (sapogenins). Saponins possess many biological activities, including conferring potential health benefits for humans. However, most of the steps specific for the biosynthesis of triterpene saponins remain uncharacterized at the molecular level. Here, we use comprehensive gene expression clustering analysis to identify candidate genes involved in the elaboration, hydroxylation, and glycosylation of the triterpene skeleton in the model legume Medicago truncatula. Four candidate uridine diphosphate glycosyltransferases were expressed in Escherichia coli, one of which (UGT73F3) showed specificity for multiple sapogenins and was confirmed to glucosylate hederagenin at the C28 position. Genetic loss-of-function studies in M. truncatula confirmed the in vivo function of UGT73F3 in saponin biosynthesis. This report provides a basis for future studies to define genetically the roles of multiple cytochromes P450 and glycosyltransferases in triterpene saponin biosynthesis in Medicago. PMID:20348429

[3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].

PubMed

Khalili, S; Rasaee, M J; Bamdad, T

2017-01-01

Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII).

Hindered rotor models with variable kinetic functions for accurate thermodynamic and kinetic predictions

NASA Astrophysics Data System (ADS)

Reinisch, Guillaume; Leyssale, Jean-Marc; Vignoles, Gérard L.

2010-10-01

We present an extension of some popular hindered rotor (HR) models, namely, the one-dimensional HR (1DHR) and the degenerated two-dimensional HR (d2DHR) models, allowing for a simple and accurate treatment of internal rotations. This extension, based on the use of a variable kinetic function in the Hamiltonian instead of a constant reduced moment of inertia, is extremely suitable in the case of rocking/wagging motions involved in dissociation or atom transfer reactions. The variable kinetic function is first introduced in the framework of a classical 1DHR model. Then, an effective temperature and potential dependent constant is proposed in the cases of quantum 1DHR and classical d2DHR models. These methods are finally applied to the atom transfer reaction SiCl3+BCl3→SiCl4+BCl2. We show, for this particular case, that a proper accounting of internal rotations greatly improves the accuracy of thermodynamic and kinetic predictions. Moreover, our results confirm (i) that using a suitably defined kinetic function appears to be very adapted to such problems; (ii) that the separability assumption of independent rotations seems justified; and (iii) that a quantum mechanical treatment is not a substantial improvement with respect to a classical one.

Resting-state functional connectivity and motor imagery brain activation

PubMed Central

Saiote, Catarina; Tacchino, Andrea; Brichetto, Giampaolo; Roccatagliata, Luca; Bommarito, Giulia; Cordano, Christian; Battaglia, Mario; Mancardi, Giovanni Luigi; Inglese, Matilde

2016-01-01

Motor imagery (MI) relies on the mental simulation of an action without any overt motor execution (ME), and can facilitate motor learning and enhance the effect of rehabilitation in patients with neurological conditions. While functional magnetic resonance imaging (fMRI) during MI and ME reveals shared cortical representations, the role and functional relevance of the resting-state functional connectivity (RSFC) of brain regions involved in MI is yet unknown. Here, we performed resting-state fMRI followed by fMRI during ME and MI with the dominant hand. We used a behavioral chronometry test to measure ME and MI movement duration and compute an index of performance (IP). Then, we analyzed the voxel-matched correlation between the individual MI parameter estimates and seed-based RSFC maps in the MI network to measure the correspondence between RSFC and MI fMRI activation. We found that inter-individual differences in intrinsic connectivity in the MI network predicted several clusters of activation. Taken together, present findings provide first evidence that RSFC within the MI network is predictive of the activation of MI brain regions, including those associated with behavioral performance, thus suggesting a role for RSFC in obtaining a deeper understanding of neural substrates of MI and of MI ability. PMID:27273577

Bioinformatic analysis of Msx1 and Msx2 involved in craniofacial development.

PubMed

Dai, Jiewen; Mou, Zhifang; Shen, Shunyao; Dong, Yuefu; Yang, Tong; Shen, Steve Guofang

2014-01-01

Msx1 and Msx2 were revealed to be candidate genes for some craniofacial deformities, such as cleft lip with/without cleft palate (CL/P) and craniosynostosis. Many other genes were demonstrated to have a cross-talk with MSX genes in causing these defects. However, there is no systematic evaluation for these MSX gene-related factors. In this study, we performed systematic bioinformatic analysis for MSX genes by combining using GeneDecks, DAVID, and STRING database, and the results showed that there were numerous genes related to MSX genes, such as Irf6, TP63, Dlx2, Dlx5, Pax3, Pax9, Bmp4, Tgf-beta2, and Tgf-beta3 that have been demonstrated to be involved in CL/P, and Fgfr2, Fgfr1, Fgfr3, and Twist1 that were involved in craniosynostosis. Many of these genes could be enriched into different gene groups involved in different signaling ways, different craniofacial deformities, and different biological process. These findings could make us analyze the function of MSX gens in a gene network. In addition, our findings showed that Sumo, a novel gene whose polymorphisms were demonstrated to be associated with nonsyndromic CL/P by genome-wide association study, has protein-protein interaction with MSX1, which may offer us an alternative method to perform bioinformatic analysis for genes found by genome-wide association study and can make us predict the disrupted protein function due to the mutation in a gene DNA sequence. These findings may guide us to perform further functional studies in the future.

Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations

NASA Astrophysics Data System (ADS)

Selwa, Edithe; Elisée, Eddy; Zavala, Agustin; Iorga, Bogdan I.

2018-01-01

Our participation to the D3R Grand Challenge 2 involved a protocol in two steps, with an initial analysis of the available structural data from the PDB allowing the selection of the most appropriate combination of docking software and scoring function. Subsequent docking calculations showed that the pose prediction can be carried out with a certain precision, but this is dependent on the specific nature of the ligands. The correct ranking of docking poses is still a problem and cannot be successful in the absence of good pose predictions. Our free energy calculations on two different subsets provided contrasted results, which might have the origin in non-optimal force field parameters associated with the sulfonamide chemical moiety.

Dynamic transition of neuronal firing induced by abnormal astrocytic glutamate oscillation

NASA Astrophysics Data System (ADS)

Li, Jiajia; Tang, Jun; Ma, Jun; Du, Mengmeng; Wang, Rong; Wu, Ying

2016-08-01

The gliotransmitter glutamate released from astrocytes can modulate neuronal firing by activating neuronal N-methyl-D-aspartic acid (NMDA) receptors. This enables astrocytic glutamate(AG) to be involved in neuronal physiological and pathological functions. Based on empirical results and classical neuron-glial “tripartite synapse” model, we propose a practical model to describe extracellular AG oscillation, in which the fluctuation of AG depends on the threshold of calcium concentration, and the effect of AG degradation is considered as well. We predict the seizure-like discharges under the dysfunction of AG degradation duration. Consistent with our prediction, the suppression of AG uptake by astrocytic transporters, which operates by modulating the AG degradation process, can account for the emergence of epilepsy.

Blind Pose Prediction, Scoring, and Affinity Ranking of the CSAR 2014 Dataset.

PubMed

Martiny, Virginie Y; Martz, François; Selwa, Edithe; Iorga, Bogdan I

2016-06-27

The 2014 CSAR Benchmark Exercise was focused on three protein targets: coagulation factor Xa, spleen tyrosine kinase, and bacterial tRNA methyltransferase. Our protocol involved a preliminary analysis of the structural information available in the Protein Data Bank for the protein targets, which allowed the identification of the most appropriate docking software and scoring functions to be used for the rescoring of several docking conformations datasets, as well as for pose prediction and affinity ranking. The two key points of this study were (i) the prior evaluation of molecular modeling tools that are most adapted for each target and (ii) the increased search efficiency during the docking process to better explore the conformational space of big and flexible ligands.

Application of real-time machine learning to myoelectric prosthesis control: A case series in adaptive switching.

PubMed

Edwards, Ann L; Dawson, Michael R; Hebert, Jacqueline S; Sherstan, Craig; Sutton, Richard S; Chan, K Ming; Pilarski, Patrick M

2016-10-01

Myoelectric prostheses currently used by amputees can be difficult to control. Machine learning, and in particular learned predictions about user intent, could help to reduce the time and cognitive load required by amputees while operating their prosthetic device. The goal of this study was to compare two switching-based methods of controlling a myoelectric arm: non-adaptive (or conventional) control and adaptive control (involving real-time prediction learning). Case series study. We compared non-adaptive and adaptive control in two different experiments. In the first, one amputee and one non-amputee subject controlled a robotic arm to perform a simple task; in the second, three able-bodied subjects controlled a robotic arm to perform a more complex task. For both tasks, we calculated the mean time and total number of switches between robotic arm functions over three trials. Adaptive control significantly decreased the number of switches and total switching time for both tasks compared with the conventional control method. Real-time prediction learning was successfully used to improve the control interface of a myoelectric robotic arm during uninterrupted use by an amputee subject and able-bodied subjects. Adaptive control using real-time prediction learning has the potential to help decrease both the time and the cognitive load required by amputees in real-world functional situations when using myoelectric prostheses. © The International Society for Prosthetics and Orthotics 2015.

Trivariate Modeling of Interparental Conflict and Adolescent Emotional Security: An Examination of Mother-Father-Child Dynamics.

PubMed

Cheung, Rebecca Y M; Cummings, E Mark; Zhang, Zhiyong; Davies, Patrick T

2016-11-01

Recognizing the significance of interacting family subsystems, the present study addresses how interparental conflict is linked to adolescent emotional security as a function of parental gender. A total of 272 families with a child at 12.60 years of age (133 boys, 139 girls) were invited to participate each year for three consecutive years. A multi-informant method was used, along with trivariate models to test the associations among mothers, fathers, and their adolescent children's behaviors. The findings from separate models of destructive and constructive interparental conflict revealed intricate linkages among family members. In the model of destructive interparental conflict, mothers and fathers predicted each other's conflict behaviors over time. Moreover, adolescents' exposure to negativity expressed by either parent dampened their emotional security. Consistent with child effects models, adolescent emotional insecurity predicted fathers' destructive conflict behaviors. As for the model of constructive interparental conflict, fathers predicted mothers' conflict behaviors over time. Adolescents' exposure to fathers' constructive conflict behaviors also enhanced their sense of emotional security. Consistent with child effects models, adolescent emotional security predicted mothers' and fathers' constructive conflict behaviors. These findings extended the family and the adolescent literature by indicating that family processes are multiidirectional, involving multiple dyads in the study of parents' and adolescents' functioning. Contributions of these findings to the understanding of interparental conflict and emotional security in adolescence are discussed.

The PYRIN domain: A member of the death domain-fold superfamily

PubMed Central

Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

2001-01-01

PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

Novel cis-acting element within the capsid-coding region enhances flavivirus viral-RNA replication by regulating genome cyclization.

PubMed

Liu, Zhong-Yu; Li, Xiao-Feng; Jiang, Tao; Deng, Yong-Qiang; Zhao, Hui; Wang, Hong-Jiang; Ye, Qing; Zhu, Shun-Ya; Qiu, Yang; Zhou, Xi; Qin, E-De; Qin, Cheng-Feng

2013-06-01

cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5' cyclization sequence (5'CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5'CS, and the presence of DCS-PK facilitates the formation of 5'-3' RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution.

Novel cis-Acting Element within the Capsid-Coding Region Enhances Flavivirus Viral-RNA Replication by Regulating Genome Cyclization

PubMed Central

Liu, Zhong-Yu; Li, Xiao-Feng; Jiang, Tao; Deng, Yong-Qiang; Zhao, Hui; Wang, Hong-Jiang; Ye, Qing; Zhu, Shun-Ya; Qiu, Yang; Zhou, Xi; Qin, E-De

2013-01-01

cis-Acting elements in the viral genome RNA (vRNA) are essential for the translation, replication, and/or encapsidation of RNA viruses. In this study, a novel conserved cis-acting element was identified in the capsid-coding region of mosquito-borne flavivirus. The downstream of 5′ cyclization sequence (5′CS) pseudoknot (DCS-PK) element has a three-stem pseudoknot structure, as demonstrated by structure prediction and biochemical analysis. Using dengue virus as a model, we show that DCS-PK enhances vRNA replication and that its function depends on its secondary structure and specific primary sequence. Mutagenesis revealed that the highly conserved stem 1 and loop 2, which are involved in potential loop-helix interactions, are crucial for DCS-PK function. A predicted loop 1-stem 3 base triple interaction is important for the structural stability and function of DCS-PK. Moreover, the function of DCS-PK depends on its position relative to the 5′CS, and the presence of DCS-PK facilitates the formation of 5′-3′ RNA complexes. Taken together, our results reveal that the cis-acting element DCS-PK enhances vRNA replication by regulating genome cyclization, and DCS-PK might interplay with other cis-acting elements to form a functional vRNA cyclization domain, thus playing critical roles during the flavivirus life cycle and evolution. PMID:23576500

UNC-18 Promotes Both the Anterograde Trafficking and Synaptic Function of Syntaxin

PubMed Central

McEwen, Jason M.

2008-01-01

The SM protein UNC-18 has been proposed to regulate several aspects of secretion, including synaptic vesicle docking, priming, and fusion. Here, we show that UNC-18 has a chaperone function in neurons, promoting anterograde transport of the plasma membrane soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein Syntaxin-1. In unc-18 mutants, UNC-64 (Caenorhabditis elegans Syntaxin-1) accumulates in neuronal cell bodies. Colocalization studies and analysis of carbohydrate modifications both suggest that this accumulation occurs in the endoplasmic reticulum. This trafficking defect is specific for UNC-64 Syntaxin-1, because 14 other SNARE proteins and two active zone markers were unaffected. UNC-18 binds to Syntaxin through at least two mechanisms: binding to closed Syntaxin, or to the N terminus of Syntaxin. It is unclear which of these binding modes mediates UNC-18 function in neurons. The chaperone function of UNC-18 was eliminated in double mutants predicted to disrupt both modes of Syntaxin binding, but it was unaffected in single mutants. By contrast, mutations predicted to disrupt UNC-18 binding to the N terminus of Syntaxin caused significant defects in locomotion behavior and responsiveness to cholinesterase inhibitors. Collectively, these results demonstrate the UNC-18 acts as a molecular chaperone for Syntaxin transport in neurons and that the two modes of UNC-18 binding to Syntaxin are involved in different aspects of UNC-18 function. PMID:18596236

Variation in White Matter Connectivity Predicts the Ability to Remember Faces and Discriminate Their Emotions

PubMed Central

Unger, Ashley; Alm, Kylie H.; Collins, Jessica A.; O’Leary, Jacqueline M.; Olson, Ingrid R.

2017-01-01

Objective The extended face network contains clusters of neurons that perform distinct functions on facial stimuli. Regions in the posterior ventral visual stream appear to perform basic perceptual functions on faces, while more anterior regions, such as the ventral anterior temporal lobe and amygdala, function to link mnemonic and affective information to faces. Anterior and posterior regions are interconnected by a long-range white matter tracts however it is not known if variation in connectivity of these pathways explains cognitive performance. Methods Here, we used diffusion imaging and deterministic tractography in a cohort of 28 neurologically normal adults ages 18–28 to examine microstructural properties of visual fiber pathways and their relationship to certain mnemonic and affective functions involved in face processing. We investigated how inter-individual variability in two tracts, the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), related to performance on tests of facial emotion recognition and face memory. Results Results revealed that microstructure of both tracts predicted variability in behavioral performance indexed by both tasks, suggesting that the ILF and IFOF play a role in facilitating our ability to discriminate emotional expressions in faces, as well as to remember unique faces. Variation in a control tract, the uncinate fasciculus, did not predict performance on these tasks. Conclusions These results corroborate and extend the findings of previous neuropsychology studies investigating the effects of damage to the ILF and IFOF, and demonstrate that differences in face processing abilities are related to white matter microstructure, even in healthy individuals. PMID:26888615

DFT Virtual Screening Identifies Rhodium–Amidinate Complexes As Potential Homogeneous Catalysts for Methane-to-Methanol Oxidation

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

Fu, Ross; Nielsen, Robert J.; Goddard, William A.

2014-11-11

In the search for new organometallic catalysts for low-temperature selective conversion of CH4 to CH3OH, we apply quantum mechanical virtual screening to select the optimum combination of ligand and solvent on rhodium to achieve low barriers for CH4 activation and functionalization to recommend for experimental validation. Here, we considered Rh because its lower electronegativity compared with Pt and Pd may allow it to avoid poisoning by coordinating media. We report quantum mechanical predictions (including implicit and explicit solvation) of the mechanisms for RhIII(NN) and RhIII(NNF) complexes [where (NN) = bis(N-phenyl)benzylamidinate and (NNF) = bis(N-pentafluorophenyl)pentafluorobenzylamidinate] to catalytically activate and functionalize methanemore » using trifluoroacetic acid (TFAH) or water as a solvent. In particular, we designed the (NNF) ligand as a more electrophilic analogue to the (NN) ligand, and our results predict the lowest transition state barrier (ΔG‡ = 27.6 kcal/mol) for methane activation in TFAH from a pool of four different classes of ligands. To close the catalytic cycle, the functionalization of methylrhodium intermediates was also investigated, involving carbon–oxygen bond formation via SN2 attack by solvent, or SR2 attack by a vanadium oxo. Activation barriers for the functionalization of methylrhodium intermediates via nucleophilic attack are lower when the solvent is water, but CH4 activation barriers are higher. In addition, we have found a correlation between CH4 activation barriers and rhodium–methyl bond energies that allow us to predict the activation transition state energies for future ligands, as well.« less

Preoperative PROMIS Scores Predict Postoperative Success in Foot and Ankle Patients.

PubMed

Ho, Bryant; Houck, Jeff R; Flemister, Adolph S; Ketz, John; Oh, Irvin; DiGiovanni, Benedict F; Baumhauer, Judith F

2016-09-01

The use of patient-reported outcomes continues to expand beyond the scope of clinical research to involve standard of care assessments across orthopedic practices. It is currently unclear how to interpret and apply this information in the daily care of patients in a foot and ankle clinic. We prospectively examined the relationship between preoperative patient-reported outcomes (PROMIS Physical Function, Pain Interference and Depression scores), determined minimal clinical important differences for these values, and assessed if these preoperative values were predictors of improvement after operative intervention. Prospective collection of all consecutive patient visits to a multisurgeon tertiary foot and ankle clinic was obtained between February 2015 and April 2016. This consisted of 16 023 unique visits across 7996 patients, with 3611 new patients. Patients undergoing elective operative intervention were identified by ICD-9 and CPT code. PROMIS physical function, pain interference, and depression scores were assessed at initial and follow-up visits. Minimum clinically important differences (MCIDs) were calculated using a distribution-based method. Receiver operating characteristic (ROC) curves were calculated to determine whether preoperative PROMIS scores were predictive of achieving MCID. Cutoff values for PROMIS scores that would predict achieving MCID and not achieving MCID with 95% specificity were determined. Prognostic pre- and posttest probabilities based off these cutoffs were calculated. Patients with a minimum of 7-month follow-up (mean 9.9) who completed all PROMIS domains were included, resulting in 61 patients. ROC curves demonstrated that preoperative physical function scores were predictive of postoperative improvement in physical function (area under the curve [AUC] 0.83). Similarly, preoperative pain interference scores were predictive of postoperative pain improvement (AUC 0.73) and preoperative depression scores were also predictive of postoperative depression improvement (AUC 0.74). Patients with preoperative physical function T score below 29.7 had an 83% probability of achieving a clinically meaningful improvement in function as defined by MCID. Patients with preoperative physical function T score above 42 had a 94% probability of failing to achieve MCID. Patients with preoperative pain above 67.2 had a 66% probability of achieving MCID, whereas patients with preoperative pain below 55 had a 95% probability of failing to achieve MCID. Patients with preoperative depression below 41.5 had a 90% probability of failing to achieve MCID. Patient-reported outcomes (PROMIS) scores obtained preoperatively predicted improvement in foot and ankle surgery. Threshold levels in physical function, pain interference, and depression can be shared with patients as they decide whether surgery is a good option and helps place a numerical value on patient expectations. Physical function scores below 29.7 were likely to improve with surgery, whereas those patients with scores above 42 were unlikely to make gains in function. Patients with pain scores less than 55 were similarly unlikely to improve, whereas those with scores above 67 had clinically significant pain reduction postoperatively. Reported prognostic cutoff values help to provide guidance to both the surgeon and the patient and can aid in shared decision making for treatment. Level II, prognostic study. © The Author(s) 2016.

Role of the superior colliculus in choosing mixed-strategy saccades.

PubMed

Thevarajah, Dhushan; Mikulić, Areh; Dorris, Michael C

2009-02-18

Game theory outlines optimal response strategies during mixed-strategy competitions. The neural processes involved in choosing individual strategic actions, however, remain poorly understood. Here, we tested whether the superior colliculus (SC), a brain region critical for generating sensory-guided saccades, is also involved in choosing saccades under strategic conditions. Monkeys were free to choose either of two saccade targets as they competed against a computer opponent during the mixed-strategy game "matching pennies." The accuracy with which presaccadic SC activity predicted upcoming choice gradually increased in the time leading up to the saccade. Probing the SC with suprathreshold stimulation demonstrated that these evolving signals were functionally involved in preparing strategic saccades. Finally, subthreshold stimulation of the SC increased the likelihood that contralateral saccades were selected. Together, our results suggest that motor regions of the brain play an active role in choosing strategic actions rather than passively executing those prespecified by upstream executive regions.

WE-AB-202-02: Incorporating Regional Ventilation Function in Predicting Radiation Fibrosis After Concurrent Chemoradiotherapy for Lung Cancer

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

Lan, F; Jeudy, J; Tseng, H

Purpose: To investigate the incorporation of pre-therapy regional ventilation function in predicting radiation fibrosis (RF) in stage III non-small-cell lung cancer (NSCLC) patients treated with concurrent thoracic chemoradiotherapy. Methods: 37 stage III NSCLC patients were retrospectively studied. Patients received one cycle of cisplatin-gemcitabine, followed by two to three cycles of cisplatin-etoposide concurrently with involved-field thoracic radiotherapy between 46 and 66 Gy (2 Gy per fraction). Pre-therapy regional ventilation images of the lung were derived from 4DCT via a density-change-based image registration algorithm with mass correction. RF was evaluated at 6-months post-treatment using radiographic scoring based on airway dilation and volumemore » loss. Three types of ipsilateral lung metrics were studied: (1) conventional dose-volume metrics (V20, V30, V40, and mean-lung-dose (MLD)), (2) dose-function metrics (fV20, fV30, fV40, and functional mean-lung-dose (fMLD) generated by combining regional ventilation and dose), and (3) dose-subvolume metrics (sV20, sV30, sV40, and subvolume mean-lung-dose (sMLD) defined as the dose-volume metrics computed on the sub-volume of the lung with at least 60% of the quantified maximum ventilation status). Receiver operating characteristic (ROC) curve analysis and logistic regression analysis were used to evaluate the predictability of these metrics for RF. Results: In predicting airway dilation, the area under the ROC curve (AUC) values for (V20, MLD), (fV20, fMLD), and (sV20, and sMLD) were (0.76, 0.70), (0.80, 0.74) and (0.82, 0.80), respectively. The logistic regression p-values were (0.09, 0.18), (0.02, 0.05) and (0.004, 0.006), respectively. With regard to volume loss, the corresponding AUC values for these metrics were (0.66, 0.57), (0.67, 0.61) and (0.71, 0.69), and p-values were (0.95, 0.90), (0.43, 0.64) and (0.08, 0.12), respectively. Conclusion: The inclusion of regional ventilation function improved predictability of radiation fibrosis. Dose-subvolume metrics provided a promising method for incorporating functional information into the conventional dose-volume parameters for outcome assessment.« less

Circular RNA expression profile of articular chondrocytes in an IL-1β-induced mouse model of osteoarthritis.

PubMed

Zhou, Zhibin; Du, Di; Chen, Aimin; Zhu, Lei

2018-02-20

Osteoarthritis (OA) is a widely prevalent degenerative joint disease characterized by articular cartilage degradation and joint inflammation. The pathogenesis of OA remains unclear, leading to a lack of effective treatment. Previous studies have reported that circular RNAs (circRNAs) are involved in the development of various diseases. However, the function of circRNAs and their roles in OA is largely unknown. Therefore, we aimed to investigate changes in circRNA expression and predict their functions in OA by using bioinformatics analysis. An OA model was established in mouse articular chondrocytes (MACs) treated by interleukin-1β (IL-1β), and then the circRNA profile was screened by Next Generation Sequencing. By comparing circRNA expression in IL-1β- treated MACs and normal controls, differentially expressed circRNAs were identified during OA pathogenesis, and differential expression levels of selected circRNAs were validated by qRT-PCR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were employed to predict the functions of these circRNAs. Because circRNAs can act as "miRNA sponges", we also constructed a circRNA-miRNA network to predict their functions. A total of 255 circRNAs were found to be differentially expressed in IL-1β-treated MACs (p≤0.05; fold-change≥2) from the expression of the normal controls. Among them, 119 circRNAs were significantly up-regulated, and the other 136 were down-regulated. Seven circRNAs were randomly selected to verify the reliability of these profiles by quantitative qRT-PCR. After obtaining the parental genes of differentially expressed circRNA, the top 30 enrichment GO entries and KEGG pathways were annotated. Then, two significantly differentially expressed circRNAs (mmu-circRNA-30365 and mmu-circRNA-36866) were identified and selected for further analysis, meanwhile a circRNA-miRNA regulation network was created and the top five most likely functional-related target miRNAs of the circRNAs were collected. Although the exact mechanisms and biological functions of these circRNAs in the development of OA need further exploration, our findings do suggest that the differentially expressed circRNAs were involved in the pathogenesis of OA. Thus, our study brings us closer to understanding the pathogenic mechanisms and finding new molecular targets for the clinical treatment of osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

The timing of associative memory formation: frontal lobe and anterior medial temporal lobe activity at associative binding predicts memory

PubMed Central

Hales, J. B.

2011-01-01

The process of associating items encountered over time and across variable time delays is fundamental for creating memories in daily life, such as for stories and episodes. Forming associative memory for temporally discontiguous items involves medial temporal lobe structures and additional neocortical processing regions, including prefrontal cortex, parietal lobe, and lateral occipital regions. However, most prior memory studies, using concurrently presented stimuli, have failed to examine the temporal aspect of successful associative memory formation to identify when activity in these brain regions is predictive of associative memory formation. In the current study, functional MRI data were acquired while subjects were shown pairs of sequentially presented visual images with a fixed interitem delay within pairs. This design allowed the entire time course of the trial to be analyzed, starting from onset of the first item, across the 5.5-s delay period, and through offset of the second item. Subjects then completed a postscan recognition test for the items and associations they encoded during the scan and their confidence for each. After controlling for item-memory strength, we isolated brain regions selectively involved in associative encoding. Consistent with prior findings, increased regional activity predicting subsequent associative memory success was found in anterior medial temporal lobe regions of left perirhinal and entorhinal cortices and in left prefrontal cortex and lateral occipital regions. The temporal separation within each pair, however, allowed extension of these findings by isolating the timing of regional involvement, showing that increased response in these regions occurs during binding but not during maintenance. PMID:21248058

Functional Imaging Biomarkers: Potential to Guide an Individualised Approach to Radiotherapy.

PubMed

Prestwich, R J D; Vaidyanathan, S; Scarsbrook, A F

2015-10-01

The identification of robust prognostic and predictive biomarkers would transform the ability to implement an individualised approach to radiotherapy. In this regard, there has been a surge of interest in the use of functional imaging to assess key underlying biological processes within tumours and their response to therapy. Importantly, functional imaging biomarkers hold the potential to evaluate tumour heterogeneity/biology both spatially and temporally. An ever-increasing range of functional imaging techniques is now available primarily involving positron emission tomography and magnetic resonance imaging. Small-scale studies across multiple tumour types have consistently been able to correlate changes in functional imaging parameters during radiotherapy with disease outcomes. Considerable challenges remain before the implementation of functional imaging biomarkers into routine clinical practice, including the inherent temporal variability of biological processes within tumours, reproducibility of imaging, determination of optimal imaging technique/combinations, timing during treatment and design of appropriate validation studies. Copyright © 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Recursive feature elimination for biomarker discovery in resting-state functional connectivity.

PubMed

Ravishankar, Hariharan; Madhavan, Radhika; Mullick, Rakesh; Shetty, Teena; Marinelli, Luca; Joel, Suresh E

2016-08-01

Biomarker discovery involves finding correlations between features and clinical symptoms to aid clinical decision. This task is especially difficult in resting state functional magnetic resonance imaging (rs-fMRI) data due to low SNR, high-dimensionality of images, inter-subject and intra-subject variability and small numbers of subjects compared to the number of derived features. Traditional univariate analysis suffers from the problem of multiple comparisons. Here, we adopt an alternative data-driven method for identifying population differences in functional connectivity. We propose a machine-learning approach to down-select functional connectivity features associated with symptom severity in mild traumatic brain injury (mTBI). Using this approach, we identified functional regions with altered connectivity in mTBI. including the executive control, visual and precuneus networks. We compared functional connections at multiple resolutions to determine which scale would be more sensitive to changes related to patient recovery. These modular network-level features can be used as diagnostic tools for predicting disease severity and recovery profiles.

Thalamo-Sensorimotor Functional Connectivity Correlates with World Ranking of Olympic, Elite, and High Performance Athletes.

PubMed

Huang, Zirui; Davis, Henry Hap; Wolff, Annemarie; Northoff, Georg

2017-01-01

Brain plasticity studies have shown functional reorganization in participants with outstanding motor expertise. Little is known about neural plasticity associated with exceptionally long motor training or of its predictive value for motor performance excellence. The present study utilised resting-state functional magnetic resonance imaging (rs-fMRI) in a unique sample of world-class athletes: Olympic, elite, and internationally ranked swimmers ( n = 30). Their world ranking ranged from 1st to 250th: each had prepared for participation in the Olympic Games. Combining rs-fMRI graph-theoretical and seed-based functional connectivity analyses, it was discovered that the thalamus has its strongest connections with the sensorimotor network in elite swimmers with the highest world rankings (career best rank: 1-35). Strikingly, thalamo-sensorimotor functional connections were highly correlated with the swimmers' motor performance excellence, that is, accounting for 41% of the individual variance in best world ranking. Our findings shed light on neural correlates of long-term athletic performance involving thalamo-sensorimotor functional circuits.

Functional neuroimaging of emotional learning and autonomic reactions.

PubMed

Peper, Martin; Herpers, Martin; Spreer, Joachim; Hennig, Jürgen; Zentner, Josef

2006-06-01

This article provides a selective overview of the functional neuroimaging literature with an emphasis on emotional activation processes. Emotions are fast and flexible response systems that provide basic tendencies for adaptive action. From the range of involved component functions, we first discuss selected automatic mechanisms that control basic adaptational changes. Second, we illustrate how neuroimaging work has contributed to the mapping of the network components associated with basic emotion families (fear, anger, disgust, happiness), and secondary dimensional concepts that organise the meaning space for subjective experience and verbal labels (emotional valence, activity/intensity, approach/withdrawal, etc.). Third, results and methodological difficulties are discussed in view of own neuroimaging experiments that investigated the component functions involved in emotional learning. The amygdala, prefrontal cortex, and striatum form a network of reciprocal connections that show topographically distinct patterns of activity as a correlate of up and down regulation processes during an emotional episode. Emotional modulations of other brain systems have attracted recent research interests. Emotional neuroimaging calls for more representative designs that highlight the modulatory influences of regulation strategies and socio-cultural factors responsible for inhibitory control and extinction. We conclude by emphasising the relevance of the temporal process dynamics of emotional activations that may provide improved prediction of individual differences in emotionality.

Profiling of proteins secreted in the bovine oviduct reveals diverse functions of this luminal microenvironment.

PubMed

Pillai, Viju Vijayan; Weber, Darren M; Phinney, Brett S; Selvaraj, Vimal

2017-01-01

The oviductal microenvironment is a site for key events that involve gamete maturation, fertilization and early embryo development. Secretions into the oviductal lumen by either the lining epithelium or by transudation of plasma constituents are known to contain elements conducive for reproductive success. Although previous studies have identified some of these factors involved in reproduction, knowledge of secreted proteins in the oviductal fluid remains rudimentary with limited definition of function even in extensively studied species like cattle. In this study, we used a shotgun proteomics approach followed by bioinformatics sequence prediction to identify secreted proteins present in the bovine oviductal fluid (ex vivo) and secretions from the bovine oviductal epithelial cells (in vitro). From a total of 2087 proteins identified, 266 proteins could be classified as secreted, 109 (41%) of which were common for both in vivo and in vitro conditions. Pathway analysis indicated different classes of proteins that included growth factors, metabolic regulators, immune modulators, enzymes, and extracellular matrix components. Functional analysis revealed mechanisms in the oviductal lumen linked to immune homeostasis, gamete maturation, fertilization and early embryo development. These results point to several novel components that work together with known elements mediating functional homeostasis, and highlight the diversity of machinery associated with oviductal physiology and early events in cattle fertility.

The Functional Landscape of Hsp27 Reveals New Cellular Processes such as DNA Repair and Alternative Splicing and Proposes Novel Anticancer Targets*

PubMed Central

Katsogiannou, Maria; Andrieu, Claudia; Baylot, Virginie; Baudot, Anaïs; Dusetti, Nelson J.; Gayet, Odile; Finetti, Pascal; Garrido, Carmen; Birnbaum, Daniel; Bertucci, François; Brun, Christine; Rocchi, Palma

2014-01-01

Previously, we identified the stress-induced chaperone, Hsp27, as highly overexpressed in castration-resistant prostate cancer and developed an Hsp27 inhibitor (OGX-427) currently tested in phase I/II clinical trials as a chemosensitizing agent in different cancers. To better understand the Hsp27 poorly-defined cytoprotective functions in cancers and increase the OGX-427 pharmacological safety, we established the Hsp27-protein interaction network using a yeast two-hybrid approach and identified 226 interaction partners. As an example, we showed that targeting Hsp27 interaction with TCTP, a partner protein identified in our screen increases therapy sensitivity, opening a new promising field of research for therapeutic approaches that could decrease or abolish toxicity for normal cells. Results of an in-depth bioinformatics network analysis allying the Hsp27 interaction map into the human interactome underlined the multifunctional character of this protein. We identified interactions of Hsp27 with proteins involved in eight well known functions previously related to Hsp27 and uncovered 17 potential new ones, such as DNA repair and RNA splicing. Validation of Hsp27 involvement in both processes in human prostate cancer cells supports our system biology-predicted functions and provides new insights into Hsp27 roles in cancer cells. PMID:25277244

Determining the folding and binding free energy of DNA-based nanodevices and nanoswitches using urea titration curves

PubMed Central

Idili, Andrea

2017-01-01

Abstract DNA nanotechnology takes advantage of the predictability of DNA interactions to build complex DNA-based functional nanoscale structures. However, when DNA functional and responsive units that are based on non-canonical DNA interactions are employed it becomes quite challenging to predict, understand and control their thermodynamics. In response to this limitation, here we demonstrate the use of isothermal urea titration experiments to estimate the free energy involved in a set of DNA-based systems ranging from unimolecular DNA-based nanoswitches to more complex DNA folds (e.g. aptamers) and nanodevices. We propose here a set of fitting equations that allow to analyze the urea titration curves of these DNA responsive units based on Watson–Crick and non-canonical interactions (stem-loop, G-quadruplex, triplex structures) and to correctly estimate their relative folding and binding free energy values under different experimental conditions. The results described herein will pave the way toward the use of urea titration experiments in the field of DNA nanotechnology to achieve easier and more reliable thermodynamic characterization of DNA-based functional responsive units. More generally, our results will be of general utility to characterize other complex supramolecular systems based on different biopolymers. PMID:28605461

Computational approaches for de novo design and redesign of metal-binding sites on proteins.

PubMed

Akcapinar, Gunseli Bayram; Sezerman, Osman Ugur

2017-04-28

Metal ions play pivotal roles in protein structure, function and stability. The functional and structural diversity of proteins in nature expanded with the incorporation of metal ions or clusters in proteins. Approximately one-third of these proteins in the databases contain metal ions. Many biological and chemical processes in nature involve metal ion-binding proteins, aka metalloproteins. Many cellular reactions that underpin life require metalloproteins. Most of the remarkable, complex chemical transformations are catalysed by metalloenzymes. Realization of the importance of metal-binding sites in a variety of cellular events led to the advancement of various computational methods for their prediction and characterization. Furthermore, as structural and functional knowledgebase about metalloproteins is expanding with advances in computational and experimental fields, the focus of the research is now shifting towards de novo design and redesign of metalloproteins to extend nature's own diversity beyond its limits. In this review, we will focus on the computational toolbox for prediction of metal ion-binding sites, de novo metalloprotein design and redesign. We will also give examples of tailor-made artificial metalloproteins designed with the computational toolbox. © 2017 The Author(s).

Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults.

PubMed

Spreng, R Nathan; Cassidy, Benjamin N; Darboh, Bri S; DuPre, Elizabeth; Lockrow, Amber W; Setton, Roni; Turner, Gary R

2017-10-01

Age-related brain changes leading to altered socioemotional functioning may increase vulnerability to financial exploitation. If confirmed, this would suggest a novel mechanism leading to heightened financial exploitation risk in older adults. Development of predictive neural markers could facilitate increased vigilance and prevention. In this preliminary study, we sought to identify structural and functional brain differences associated with financial exploitation in older adults. Financially exploited older adults (n = 13, 7 female) and a matched cohort of older adults who had been exposed to, but avoided, a potentially exploitative situation (n = 13, 7 female) were evaluated. Using magnetic resonance imaging, we examined cortical thickness and resting state functional connectivity. Behavioral data were collected using standardized cognitive assessments, self-report measures of mood and social functioning. The exploited group showed cortical thinning in anterior insula and posterior superior temporal cortices, regions associated with processing affective and social information, respectively. Functional connectivity encompassing these regions, within default and salience networks, was reduced, while between network connectivity was increased. Self-reported anger and hostility was higher for the exploited group. We observed financial exploitation associated with brain differences in regions involved in socioemotional functioning. These exploratory and preliminary findings suggest that alterations in brain regions implicated in socioemotional functioning may be a marker of financial exploitation risk. Large-scale, prospective studies are necessary to validate this neural mechanism, and develop predictive markers for use in clinical practice. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

Planning for robust reserve networks using uncertainty analysis

USGS Publications Warehouse

Moilanen, A.; Runge, M.C.; Elith, Jane; Tyre, A.; Carmel, Y.; Fegraus, E.; Wintle, B.A.; Burgman, M.; Ben-Haim, Y.

2006-01-01

Planning land-use for biodiversity conservation frequently involves computer-assisted reserve selection algorithms. Typically such algorithms operate on matrices of species presence?absence in sites, or on species-specific distributions of model predicted probabilities of occurrence in grid cells. There are practically always errors in input data?erroneous species presence?absence data, structural and parametric uncertainty in predictive habitat models, and lack of correspondence between temporal presence and long-run persistence. Despite these uncertainties, typical reserve selection methods proceed as if there is no uncertainty in the data or models. Having two conservation options of apparently equal biological value, one would prefer the option whose value is relatively insensitive to errors in planning inputs. In this work we show how uncertainty analysis for reserve planning can be implemented within a framework of information-gap decision theory, generating reserve designs that are robust to uncertainty. Consideration of uncertainty involves modifications to the typical objective functions used in reserve selection. Search for robust-optimal reserve structures can still be implemented via typical reserve selection optimization techniques, including stepwise heuristics, integer-programming and stochastic global search.

Understanding the link between exposure to violence and aggression in justice-involved adolescents.

PubMed

Wall Myers, Tina D; Salcedo, Abigail; Frick, Paul J; Ray, James V; Thornton, Laura C; Steinberg, Laurence; Cauffman, Elizabeth

2018-05-01

The current study advanced research on the link between community violence exposure and aggression by comparing the effects of violence exposure on different functions of aggression and by testing four potential (i.e., callous-unemotional traits, consideration of others, impulse control, and anxiety) mediators of this relationship. Analyses were conducted in an ethnically/racially diverse sample of 1,216 male first-time juvenile offenders (M = 15.30 years, SD = 1.29). Our results indicated that violence exposure had direct effects on both proactive and reactive aggression 18 months later. The predictive link of violence exposure to proactive aggression was no longer significant after controlling for proactive aggression at baseline and the overlap with reactive aggression. In contrast, violence exposure predicted later reactive aggression even after controlling for baseline reactive aggression and the overlap with proactive aggression. Mediation analyses of the association between violence exposure and reactive aggression indicated indirect effects through all potential mediators, but the strongest indirect effect was through impulse control. The findings help to advance knowledge on the consequences of community violence exposure on justice-involved youth.

Characterization of Enzymatic Activity of MlrB and MlrC Proteins Involved in Bacterial Degradation of Cyanotoxins Microcystins.

PubMed

Dziga, Dariusz; Zielinska, Gabriela; Wladyka, Benedykt; Bochenska, Oliwia; Maksylewicz, Anna; Strzalka, Wojciech; Meriluoto, Jussi

2016-03-16

Bacterial degradation of toxic microcystins produced by cyanobacteria is a common phenomenon. However, our understanding of the mechanisms of these processes is rudimentary. In this paper several novel discoveries regarding the action of the enzymes of the mlr cluster responsible for microcystin biodegradation are presented using recombinant proteins. In particular, the predicted active sites of the recombinant MlrB and MlrC were analyzed using functional enzymes and their inactive muteins. A new degradation intermediate, a hexapeptide derived from linearized microcystins by MlrC, was discovered. Furthermore, the involvement of MlrA and MlrB in further degradation of the hexapeptides was confirmed and a corrected biochemical pathway of microcystin biodegradation has been proposed.

De novo pathogenic variants in CHAMP1 are associated with global developmental delay, intellectual disability, and dysmorphic facial features.

PubMed

Tanaka, Akemi J; Cho, Megan T; Retterer, Kyle; Jones, Julie R; Nowak, Catherine; Douglas, Jessica; Jiang, Yong-Hui; McConkie-Rosell, Allyn; Schaefer, G Bradley; Kaylor, Julie; Rahman, Omar A; Telegrafi, Aida; Friedman, Bethany; Douglas, Ganka; Monaghan, Kristin G; Chung, Wendy K

2016-01-01

We identified five unrelated individuals with significant global developmental delay and intellectual disability (ID), dysmorphic facial features and frequent microcephaly, and de novo predicted loss-of-function variants in chromosome alignment maintaining phosphoprotein 1 (CHAMP1). Our findings are consistent with recently reported de novo mutations in CHAMP1 in five other individuals with similar features. CHAMP1 is a zinc finger protein involved in kinetochore-microtubule attachment and is required for regulating the proper alignment of chromosomes during metaphase in mitosis. Mutations in CHAMP1 may affect cell division and hence brain development and function, resulting in developmental delay and ID.

Mirror neuron system as the joint from action to language.

PubMed

Chen, Wei; Yuan, Ti-Fei

2008-08-01

Mirror neuron system (MNS) represents one of the most important discoveries of cognitive neuroscience in the past decade, and it has been found to involve in multiple aspects of brain functions including action understanding, imitation, language understanding, empathy, action prediction and speech evolution. This manuscript reviewed the function of MNS in action understanding as well as language evolution, and specifically assessed its roles as the bridge from body language to fluent speeches. Then we discussed the speech defects of autism patients due to the disruption of MNS. Finally, given that MNS is plastic in adult brain, we proposed MNS targeted therapy provides an efficient rehabilitation approach for brain damages conditions as well as autism patients.