How Do Families Help or Hinder the Emergence of Early Executive Function?

ERIC Educational Resources Information Center

Hughes, Claire H.; Ensor, Rosie A.

2009-01-01

This chapter describes longitudinal findings from a socially diverse sample of 125 British children seen at ages two and four. Four models of social influence on executive function are tested, using multiple measures of family life as well as comprehensive assessments of children's executive functions. Our results confirm the importance of…

Functional competency and cognitive ability in mild Alzheimer's disease: relationship between ADL assessed by a relative/ carer-rated scale and neuropsychological performance.

PubMed

Matsuda, Osamu; Saito, Masahiko

2005-06-01

Alzheimer's disease (AD) is characterized by multiple cognitive deficits and affects functional competency to perform daily activities (ADL). As this may contribute to the patient's overall disability, it is important to identify factors that compromise competency. The relationship between different cognitive domains and functional activities in AD was studied. The functional competency of 73 Japanese AD patients, most with mild dementia, was assessed using a 27-item relative/carer-rating scale covering 7 ADL: managing finances, using transportation, taking precautions, self-care, housekeeping, communication and taking medicine. Cognitive assessment used 16 neuropsychological tests from the Japanese version of the WAIS-R and COGNISTAT, covering 9 cognitive domains: orientation, attention, episodic memory, semantic memory, language, visuoperceptual and construction abilities, computational ability, abstract thinking, and psychomotor speed. Multiple regression analysis by the stepwise method indicated that functional competency could, for the most part, be predicted from test scores for orientation, abstract thinking and psychomotor speed. The results of this study suggest that impairment of these three cognitive domains plays an important role in the functional deterioration of AD.

Rethinking the Discovery Function of Proof within the Context of Proofs and Refutations

ERIC Educational Resources Information Center

Komatsu, Kotaro; Tsujiyama, Yosuke; Sakamaki, Aruta

2014-01-01

Proof and proving are important components of school mathematics and have multiple functions in mathematical practice. Among these functions of proof, this paper focuses on the discovery function that refers to invention of a new statement or conjecture by reflecting on or utilizing a constructed proof. Based on two cases in which eighth and ninth…

Factors predicting work outcome in Japanese patients with schizophrenia: role of multiple functioning levels.

PubMed

Sumiyoshi, Chika; Harvey, Philip D; Takaki, Manabu; Okahisa, Yuko; Sato, Taku; Sora, Ichiro; Nuechterlein, Keith H; Subotnik, Kenneth L; Sumiyoshi, Tomiki

2015-09-01

Functional outcomes in individuals with schizophrenia suggest recovery of cognitive, everyday, and social functioning. Specifically improvement of work status is considered to be most important for their independent living and self-efficacy. The main purposes of the present study were 1) to identify which outcome factors predict occupational functioning, quantified as work hours, and 2) to provide cut-offs on the scales for those factors to attain better work status. Forty-five Japanese patients with schizophrenia and 111 healthy controls entered the study. Cognition, capacity for everyday activities, and social functioning were assessed by the Japanese versions of the MATRICS Cognitive Consensus Battery (MCCB), the UCSD Performance-based Skills Assessment-Brief (UPSA-B), and the Social Functioning Scale Individuals' version modified for the MATRICS-PASS (Modified SFS for PASS), respectively. Potential factors for work outcome were estimated by multiple linear regression analyses (predicting work hours directly) and a multiple logistic regression analyses (predicting dichotomized work status based on work hours). ROC curve analyses were performed to determine cut-off points for differentiating between the better- and poor work status. The results showed that a cognitive component, comprising visual/verbal learning and emotional management, and a social functioning component, comprising independent living and vocational functioning, were potential factors for predicting work hours/status. Cut-off points obtained in ROC analyses indicated that 60-70% achievements on the measures of those factors were expected to maintain the better work status. Our findings suggest that improvement on specific aspects of cognitive and social functioning are important for work outcome in patients with schizophrenia.

A Case History and Comparative Study of a Multiple Personality.

ERIC Educational Resources Information Center

Boor, Myron

The study of multiple personality is important because this disorder is severely disruptive to the individual and because further insights into other behavior disorders and the development of normal personality and behavioral functioning may emerge. A 26-year-old female experienced a conscious personality which determined the extent to which both…

OrthoVenn: a web server for genome wide comparison and annotation of orthologous clusters across multiple species

USDA-ARS?s Scientific Manuscript database

Genome wide analysis of orthologous clusters is an important component of comparative genomics studies. Identifying the overlap among orthologous clusters can enable us to elucidate the function and evolution of proteins across multiple species. Here, we report a web platform named OrthoVenn that i...

Multiple Novel Functions of Henipavirus O-glycans: The First O-glycan Functions Identified in the Paramyxovirus Family.

PubMed

Stone, Jacquelyn A; Nicola, Anthony V; Baum, Linda G; Aguilar, Hector C

2016-02-01

O-linked glycosylation is a ubiquitous protein modification in organisms belonging to several kingdoms. Both microbial and host protein glycans are used by many pathogens for host invasion and immune evasion, yet little is known about the roles of O-glycans in viral pathogenesis. Reportedly, there is no single function attributed to O-glycans for the significant paramyxovirus family. The paramyxovirus family includes many important pathogens, such as measles, mumps, parainfluenza, metapneumo- and the deadly Henipaviruses Nipah (NiV) and Hendra (HeV) viruses. Paramyxoviral cell entry requires the coordinated actions of two viral membrane glycoproteins: the attachment (HN/H/G) and fusion (F) glycoproteins. O-glycan sites in HeV G were recently identified, facilitating use of the attachment protein of this deadly paramyxovirus as a model to study O-glycan functions. We mutated the identified HeV G O-glycosylation sites and found mutants with altered cell-cell fusion, G conformation, G/F association, viral entry in a pseudotyped viral system, and, quite unexpectedly, pseudotyped viral F protein incorporation and processing phenotypes. These are all important functions of viral glycoproteins. These phenotypes were broadly conserved for equivalent NiV mutants. Thus our results identify multiple novel and pathologically important functions of paramyxoviral O-glycans, paving the way to study O-glycan functions in other paramyxoviruses and enveloped viruses.

Changes in the location of biodiversity-ecosystem function hot spots across the seafloor landscape with increasing sediment nutrient loading.

PubMed

Thrush, Simon F; Hewitt, Judi E; Kraan, Casper; Lohrer, A M; Pilditch, Conrad A; Douglas, Emily

2017-04-12

Declining biodiversity and loss of ecosystem function threatens the ability of habitats to contribute ecosystem services. However, the form of the relationship between biodiversity and ecosystem function (BEF) and how relationships change with environmental change is poorly understood. This limits our ability to predict the consequences of biodiversity loss on ecosystem function, particularly in real-world marine ecosystems that are species rich, and where multiple ecosystem functions are represented by multiple indicators. We investigated spatial variation in BEF relationships across a 300 000 m 2 intertidal sandflat by nesting experimental manipulations of sediment pore water nitrogen concentration into sites with contrasting macrobenthic community composition. Our results highlight the significance of many different elements of biodiversity associated with environmental characteristics, community structure, functional diversity, ecological traits or particular species (ecosystem engineers) to important functions of coastal marine sediments (benthic oxygen consumption, ammonium pore water concentrations and flux across the sediment-water interface). Using the BEF relationships developed from our experiment, we demonstrate patchiness across a landscape in functional performance and the potential for changes in the location of functional hot and cold spots with increasing nutrient loading that have important implications for mapping and predicating change in functionality and the concomitant delivery of ecosystem services. © 2017 The Author(s).

Multifarious Roles of Intrinsic Disorder in Proteins Illustrate Its Broad Impact on Plant Biology

PubMed Central

Sun, Xiaolin; Rikkerink, Erik H.A.; Jones, William T.; Uversky, Vladimir N.

2013-01-01

Intrinsically disordered proteins (IDPs) are highly abundant in eukaryotic proteomes. Plant IDPs play critical roles in plant biology and often act as integrators of signals from multiple plant regulatory and environmental inputs. Binding promiscuity and plasticity allow IDPs to interact with multiple partners in protein interaction networks and provide important functional advantages in molecular recognition through transient protein–protein interactions. Short interaction-prone segments within IDPs, termed molecular recognition features, represent potential binding sites that can undergo disorder-to-order transition upon binding to their partners. In this review, we summarize the evidence for the importance of IDPs in plant biology and evaluate the functions associated with intrinsic disorder in five different types of plant protein families experimentally confirmed as IDPs. Functional studies of these proteins illustrate the broad impact of disorder on many areas of plant biology, including abiotic stress, transcriptional regulation, light perception, and development. Based on the roles of disorder in the protein–protein interactions, we propose various modes of action for plant IDPs that may provide insight for future experimental approaches aimed at understanding the molecular basis of protein function within important plant pathways. PMID:23362206

Species richness effects on ecosystem multifunctionality depend on evenness, composition and spatial pattern

USGS Publications Warehouse

Maestre, F.T.; Castillo-Monroy, A. P.; Bowker, M.A.; Ochoa-Hueso, R.

2012-01-01

1. Recent studies have suggested that the simultaneous maintenance of multiple ecosystem functions (multifunctionality) is positively supported by species richness. However, little is known regarding the relative importance of other community attributes (e.g. spatial pattern, species evenness) as drivers of multifunctionality. 2. We conducted two microcosm experiments using model biological soil crust communities dominated by lichens to: (i) evaluate the joint effects and relative importance of changes in species composition, spatial pattern (clumped and random distribution of lichens), evenness (maximal and low evenness) and richness (from two to eight species) on soil functions related to nutrient cycling (β-glucosidase, urease and acid phosphatase enzymes, in situ N availability, total N, organic C, and N fixation), and (ii) assess how these community attributes affect multifunctionality. 3. Species richness, composition and spatial pattern affected multiple ecosystem functions (e.g. organic C, total N, N availability, β-glucosidase activity), albeit the magnitude and direction of their effects varied with the particular function, experiment and soil depth considered. Changes in species composition had effects on organic C, total N and the activity of β-glucosidase. Significant species richness × evenness and spatial pattern × evenness interactions were found when analysing functions such as organic C, total N and the activity of phosphatase. 4. The probability of sustaining multiple ecosystem functions increased with species richness, but this effect was largely modulated by attributes such as species evenness, composition and spatial pattern. Overall, we found that model communities with high species richness, random spatial pattern and low evenness increased multifunctionality. 5. Synthesis. Our results illustrate how different community attributes have a diverse impact on ecosystem functions related to nutrient cycling, and provide new experimental evidence illustrating the importance of the spatial pattern of organisms on ecosystem functioning. They also indicate that species richness is not the only biotic driver of multifunctionality, and that particular combinations of community attributes may be required to maximize it.

A Conserved Deubiquitinating Enzyme Uses Intrinsically Disordered Regions to Scaffold Multiple Protein Interaction Sites*

PubMed Central

Reed, Benjamin J.; Locke, Melissa N.; Gardner, Richard G.

2015-01-01

In the canonical view of protein function, it is generally accepted that the three-dimensional structure of a protein determines its function. However, the past decade has seen a dramatic growth in the identification of proteins with extensive intrinsically disordered regions (IDRs), which are conformationally plastic and do not appear to adopt single three-dimensional structures. One current paradigm for IDR function is that disorder enables IDRs to adopt multiple conformations, expanding the ability of a protein to interact with a wide variety of disparate proteins. The capacity for many interactions is an important feature of proteins that occupy the hubs of protein networks, in particular protein-modifying enzymes that usually have a broad spectrum of substrates. One such protein modification is ubiquitination, where ubiquitin is attached to proteins through ubiquitin ligases (E3s) and removed through deubiquitinating enzymes. Numerous proteomic studies have found that thousands of proteins are dynamically regulated by cycles of ubiquitination and deubiquitination. Thus, how these enzymes target their wide array of substrates is of considerable importance for understanding the function of the cell's diverse ubiquitination networks. Here, we characterize a yeast deubiquitinating enzyme, Ubp10, that possesses IDRs flanking its catalytic protease domain. We show that Ubp10 possesses multiple, distinct binding modules within its IDRs that are necessary and sufficient for directing protein interactions important for Ubp10's known roles in gene silencing and ribosome biogenesis. The human homolog of Ubp10, USP36, also has IDRs flanking its catalytic domain, and these IDRs similarly contain binding modules important for protein interactions. This work highlights the significant protein interaction scaffolding abilities of IDRs in the regulation of dynamic protein ubiquitination. PMID:26149687

Forest restoration, biodiversity and ecosystem functioning.

PubMed

Aerts, Raf; Honnay, Olivier

2011-11-24

Globally, forests cover nearly one third of the land area and they contain over 80% of terrestrial biodiversity. Both the extent and quality of forest habitat continue to decrease and the associated loss of biodiversity jeopardizes forest ecosystem functioning and the ability of forests to provide ecosystem services. In the light of the increasing population pressure, it is of major importance not only to conserve, but also to restore forest ecosystems. Ecological restoration has recently started to adopt insights from the biodiversity-ecosystem functioning (BEF) perspective. Central is the focus on restoring the relation between biodiversity and ecosystem functioning. Here we provide an overview of important considerations related to forest restoration that can be inferred from this BEF-perspective. Restoring multiple forest functions requires multiple species. It is highly unlikely that species-poor plantations, which may be optimal for above-ground biomass production, will outperform species diverse assemblages for a combination of functions, including overall carbon storage and control over water and nutrient flows. Restoring stable forest functions also requires multiple species. In particular in the light of global climatic change scenarios, which predict more frequent extreme disturbances and climatic events, it is important to incorporate insights from the relation between biodiversity and stability of ecosystem functioning into forest restoration projects. Rather than focussing on species per se, focussing on functional diversity of tree species assemblages seems appropriate when selecting tree species for restoration. Finally, also plant genetic diversity and above - below-ground linkages should be considered during the restoration process, as these likely have prominent but until now poorly understood effects at the level of the ecosystem. The BEF-approach provides a useful framework to evaluate forest restoration in an ecosystem functioning context, but it also highlights that much remains to be understood, especially regarding the relation between forest functioning on the one side and genetic diversity and above-ground-below-ground species associations on the other. The strong emphasis of the BEF-approach on functional rather than taxonomic diversity may also be the beginning of a paradigm shift in restoration ecology, increasing the tolerance towards allochthonous species.

Identifying multiple influential spreaders based on generalized closeness centrality

NASA Astrophysics Data System (ADS)

Liu, Huan-Li; Ma, Chuang; Xiang, Bing-Bing; Tang, Ming; Zhang, Hai-Feng

2018-02-01

To maximize the spreading influence of multiple spreaders in complex networks, one important fact cannot be ignored: the multiple spreaders should be dispersively distributed in networks, which can effectively reduce the redundance of information spreading. For this purpose, we define a generalized closeness centrality (GCC) index by generalizing the closeness centrality index to a set of nodes. The problem converts to how to identify multiple spreaders such that an objective function has the minimal value. By comparing with the K-means clustering algorithm, we find that the optimization problem is very similar to the problem of minimizing the objective function in the K-means method. Therefore, how to find multiple nodes with the highest GCC value can be approximately solved by the K-means method. Two typical transmission dynamics-epidemic spreading process and rumor spreading process are implemented in real networks to verify the good performance of our proposed method.

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function

PubMed Central

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D.

2009-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings. PMID:19834575

A Parallel Independent Component Analysis Approach to Investigate Genomic Influence on Brain Function.

PubMed

Liu, Jingyu; Demirci, Oguz; Calhoun, Vince D

2008-01-01

Relationships between genomic data and functional brain images are of great interest but require new analysis approaches to integrate the high-dimensional data types. This letter presents an extension of a technique called parallel independent component analysis (paraICA), which enables the joint analysis of multiple modalities including interconnections between them. We extend our earlier work by allowing for multiple interconnections and by providing important overfitting controls. Performance was assessed by simulations under different conditions, and indicated reliable results can be extracted by properly balancing overfitting and underfitting. An application to functional magnetic resonance images and single nucleotide polymorphism array produced interesting findings.

[Epidemiology of infections after liver transplantation in children].

PubMed

Pawłowska, J

2001-01-01

One of the most important problems after solid organ transplantation including liver, remains infections. Multiple risk factors play a role among which the most important are: general patients health before transplantation, prolong operative time, graft function and type of immunosuppression. The most important problems with bacterial, fungal and viral infections was described as well as treatment and profilaxis.

Identifying reprioritization response shift in a stroke caregiver population: a comparison of missing data methods.

PubMed

Sajobi, Tolulope T; Lix, Lisa M; Singh, Gurbakhshash; Lowerison, Mark; Engbers, Jordan; Mayo, Nancy E

2015-03-01

Response shift (RS) is an important phenomenon that influences the assessment of longitudinal changes in health-related quality of life (HRQOL) studies. Given that RS effects are often small, missing data due to attrition or item non-response can contribute to failure to detect RS effects. Since missing data are often encountered in longitudinal HRQOL data, effective strategies to deal with missing data are important to consider. This study aims to compare different imputation methods on the detection of reprioritization RS in the HRQOL of caregivers of stroke survivors. Data were from a Canadian multi-center longitudinal study of caregivers of stroke survivors over a one-year period. The Stroke Impact Scale physical function score at baseline, with a cutoff of 75, was used to measure patient stroke severity for the reprioritization RS analysis. Mean imputation, likelihood-based expectation-maximization imputation, and multiple imputation methods were compared in test procedures based on changes in relative importance weights to detect RS in SF-36 domains over a 6-month period. Monte Carlo simulation methods were used to compare the statistical powers of relative importance test procedures for detecting RS in incomplete longitudinal data under different missing data mechanisms and imputation methods. Of the 409 caregivers, 15.9 and 31.3 % of them had missing data at baseline and 6 months, respectively. There were no statistically significant changes in relative importance weights on any of the domains when complete-case analysis was adopted. But statistical significant changes were detected on physical functioning and/or vitality domains when mean imputation or EM imputation was adopted. There were also statistically significant changes in relative importance weights for physical functioning, mental health, and vitality domains when multiple imputation method was adopted. Our simulations revealed that relative importance test procedures were least powerful under complete-case analysis method and most powerful when a mean imputation or multiple imputation method was adopted for missing data, regardless of the missing data mechanism and proportion of missing data. Test procedures based on relative importance measures are sensitive to the type and amount of missing data and imputation method. Relative importance test procedures based on mean imputation and multiple imputation are recommended for detecting RS in incomplete data.

Reactive Attachment Disorder: Implications for School Readiness and School Functioning

ERIC Educational Resources Information Center

Schwartz, Eric; Davis, Andrew S.

2006-01-01

School readiness and functioning in children diagnosed with Reactive Attachment Disorder (RAD) are important issues due to the dramatic impact RAD has on multiple areas of development. The negative impact of impaired or disrupted early relationships, characterized by extreme neglect, abuse, parental mental illness, domestic violence, and repeated…

Sulfakinin is an important regulator of digestive processes in the migratory locust, Locusta migratoria

USDA-ARS?s Scientific Manuscript database

Sulfakinin (SK) is a sulfated insect neuropeptide that is best known for its function as a satiety factor. It displays structural and functional similarities with the vertebrate peptides gastrin and cholecystokinin. Peptidomic studies in multiple insects, crustaceans and arachnids have revealed th...

PPAR-γ in innate and adaptive lung immunity.

PubMed

Nobs, Samuel Philip; Kopf, Manfred

2018-05-16

The transcription factor PPAR-γ (peroxisome proliferator-activated receptor-γ) is a key regulator of lung immunity exhibiting multiple cell type specific roles in controlling development and function of the lung immune system. It is strictly required for the generation of alveolar macrophages by controlling differentiation of fetal lung monocyte precursors. Furthermore, it plays an important role in lung allergic inflammation by licensing lung dendritic cell t helper 2 (Th2) priming capacity as well as acting as a master transcription factor for pathogenic Th2 cells. Due to this plethora of functions and its involvement in multiple pulmonary diseases including asthma and pulmonary alveolar proteinosis, understanding the role of PPAR-γ in lung immunity is an important subject of ongoing research. ©2018 Society for Leukocyte Biology.

Abnormality in catalase import into peroxisomes leads to severe neurological disorder

PubMed Central

Sheikh, Faruk G.; Pahan, Kalipada; Khan, Mushfiquddin; Barbosa, Ernest; Singh, Inderjit

1998-01-01

Peroxisomal disorders are lethal inherited diseases caused by either defects in peroxisome assembly or dysfunction of single or multiple enzymatic function(s). The peroxisomal matrix proteins are targeted to peroxisomes via the interaction of peroxisomal targeting signal sequences 1 and 2 (PTS1 or PTS2) with their respective cytosolic receptors. We have studied human skin fibroblast cell lines that have multiple peroxisomal dysfunctions with normal packaging of PTS1 and PTS2 signal-containing proteins but lack catalase in peroxisomes. To understand the defect in targeting of catalase to peroxisomes and the loss of multiple enzyme activities, we transfected the mutant cells with normal catalase modified to contain either PTS1 or PTS2 signal sequence. We demonstrate the integrity of these pathways by targeting catalase into peroxisomes via PTS1 or PTS2 pathways. Furthermore, restoration of peroxisomal functions by targeting catalase-SKL protein (a catalase fused to the PTS1 sequence) to peroxisomes indicates that loss of multiple functions may be due to their inactivation by H2O2 or other oxygen species in these catalase-negative peroxisomes. In addition to enzyme activities, targeting of catalase-SKL chimera to peroxisomes also corrected the in situ levels of fatty acids and plasmalogens in these mutant cell lines. In normal fibroblasts treated with aminotriazole to inhibit catalase, we found that peroxisomal functions were inhibited to the level found in mutant cells, an observation that supports the conclusion that multiple peroxisomal enzyme defects in these patients are caused by H2O2 toxicity in catalase-negative peroxisomes. Moreover, targeting of catalase to peroxisomes via PTS1 and PTS2 pathways in these mutant cell lines suggests that there is another pathway for catalase import into peroxisomes and that an abnormality in this pathway manifests as a peroxisomal disease. PMID:9501198

A survey. Financial accounting and internal control functions pursued by hospital boards.

PubMed

Gavin, T A

1984-09-01

Justification for a board committee's existence is its ability to devote time to issues judged to be important by the full board. This seems to have happened. Multiple committees pursue more functions than the other committee structures. Boards lacking an FA/IC committee pursue significantly fewer functions than their counterparts with committees. Substantial respondent agreement exists on those functions most and least frequently pursued, those perceived to be most and least important, and those perceived to be most and least effectively undertaken. Distinctions between committee structures and the full board, noted in the previous paragraph, hold true with respect to the importance of functions. All board structures identified reviewing the budget and comparing it to actual results as important. Committee structures are generally more inclined to address functions related to the work of the independent auditor and the effectiveness of the hospital's system and controls than are full board structures. Functions related to the internal auditor are pursued least frequently by all FA/IC board structures. The following suggestions are made to help boards pay adequate attention to and obtain objective information about the financial affairs of their hospitals. Those boards that do not have some form of an FA/IC committee should consider starting one. Evidence shows chief financial officers have been a moving force in establishing and strengthening such committees. Boards having a joint or single committee structure should consider upgrading their structure to either a single committee or multiple committees respectively. The complexity of the healthcare environment requires that more FA/IC functions be addressed by the board. The board or its FA/IC committee(s) should meet with their independent CPA's, fiscal intermediary auditors, and internal auditors. Where the hospital lacks an internal audit function a study should be undertaken to determine the feasibility of initiating such a function. In most cases, the benefits derived from an independent, properly staffed internal audit function far exceed the cost of such a function.

Multiple Interactive Pollutants in Water Quality Trading

NASA Astrophysics Data System (ADS)

Sarang, Amin; Lence, Barbara J.; Shamsai, Abolfazl

2008-10-01

Efficient environmental management calls for the consideration of multiple pollutants, for which two main types of transferable discharge permit (TDP) program have been described: separate permits that manage each pollutant individually in separate markets, with each permit based on the quantity of the pollutant or its environmental effects, and weighted-sum permits that aggregate several pollutants as a single commodity to be traded in a single market. In this paper, we perform a mathematical analysis of TDP programs for multiple pollutants that jointly affect the environment (i.e., interactive pollutants) and demonstrate the practicality of this approach for cost-efficient maintenance of river water quality. For interactive pollutants, the relative weighting factors are functions of the water quality impacts, marginal damage function, and marginal treatment costs at optimality. We derive the optimal set of weighting factors required by this approach for important scenarios for multiple interactive pollutants and propose using an analytical elasticity of substitution function to estimate damage functions for these scenarios. We evaluate the applicability of this approach using a hypothetical example that considers two interactive pollutants. We compare the weighted-sum permit approach for interactive pollutants with individual permit systems and TDP programs for multiple additive pollutants. We conclude by discussing practical considerations and implementation issues that result from the application of weighted-sum permit programs.

Quadratures with multiple nodes, power orthogonality, and moment-preserving spline approximation

NASA Astrophysics Data System (ADS)

Milovanovic, Gradimir V.

2001-01-01

Quadrature formulas with multiple nodes, power orthogonality, and some applications of such quadratures to moment-preserving approximation by defective splines are considered. An account on power orthogonality (s- and [sigma]-orthogonal polynomials) and generalized Gaussian quadratures with multiple nodes, including stable algorithms for numerical construction of the corresponding polynomials and Cotes numbers, are given. In particular, the important case of Chebyshev weight is analyzed. Finally, some applications in moment-preserving approximation of functions by defective splines are discussed.

Multiplexed mRNA Sensing and Combinatorial-Targeted Drug Delivery Using DNA-Gold Nanoparticle Dimers.

PubMed

Kyriazi, Maria-Eleni; Giust, Davide; El-Sagheer, Afaf H; Lackie, Peter M; Muskens, Otto L; Brown, Tom; Kanaras, Antonios G

2018-04-24

The design of nanoparticulate systems which can perform multiple synergistic functions in cells with high specificity and selectivity is of great importance in applications. Here we combine recent advances in DNA-gold nanoparticle self-assembly and sensing to develop gold nanoparticle dimers that are able to perform multiplexed synergistic functions within a cellular environment. These dimers can sense two mRNA targets and simultaneously or independently deliver one or two DNA-intercalating anticancer drugs (doxorubicin and mitoxantrone) in live cells. Our study focuses on the design of sophisticated nanoparticle assemblies with multiple and synergistic functions that have the potential to advance sensing and drug delivery in cells.

Connecting Structure-Property and Structure-Function Relationships across the Disciplines of Chemistry and Biology: Exploring Student Perceptions

ERIC Educational Resources Information Center

Kohn, Kathryn P.; Underwood, Sonia M.; Cooper, Melanie M.

2018-01-01

While many university students take science courses in multiple disciplines, little is known about how they perceive common concepts from different disciplinary perspectives. Structure-property and structure-function relationships have long been considered important explanatory concepts in the disciplines of chemistry and biology, respectively.…

Image Processing, Coding, and Compression with Multiple-Point Impulse Response Functions.

NASA Astrophysics Data System (ADS)

Stossel, Bryan Joseph

1995-01-01

Aspects of image processing, coding, and compression with multiple-point impulse response functions are investigated. Topics considered include characterization of the corresponding random-walk transfer function, image recovery for images degraded by the multiple-point impulse response, and the application of the blur function to image coding and compression. It is found that although the zeros of the real and imaginary parts of the random-walk transfer function occur in continuous, closed contours, the zeros of the transfer function occur at isolated spatial frequencies. Theoretical calculations of the average number of zeros per area are in excellent agreement with experimental results obtained from computer counts of the zeros. The average number of zeros per area is proportional to the standard deviations of the real part of the transfer function as well as the first partial derivatives. Statistical parameters of the transfer function are calculated including the mean, variance, and correlation functions for the real and imaginary parts of the transfer function and their corresponding first partial derivatives. These calculations verify the assumptions required in the derivation of the expression for the average number of zeros. Interesting results are found for the correlations of the real and imaginary parts of the transfer function and their first partial derivatives. The isolated nature of the zeros in the transfer function and its characteristics at high spatial frequencies result in largely reduced reconstruction artifacts and excellent reconstructions are obtained for distributions of impulses consisting of 25 to 150 impulses. The multiple-point impulse response obscures original scenes beyond recognition. This property is important for secure transmission of data on many communication systems. The multiple-point impulse response enables the decoding and restoration of the original scene with very little distortion. Images prefiltered by the random-walk transfer function yield greater compression ratios than are obtained for the original scene. The multiple-point impulse response decreases the bit rate approximately 40-70% and affords near distortion-free reconstructions. Due to the lossy nature of transform-based compression algorithms, noise reduction measures must be incorporated to yield acceptable reconstructions after decompression.

RNA Splicing: Regulation and Dysregulation in the Heart.

PubMed

van den Hoogenhof, Maarten M G; Pinto, Yigal M; Creemers, Esther E

2016-02-05

RNA splicing represents a post-transcriptional mechanism to generate multiple functional RNAs or proteins from a single transcript. The evolution of RNA splicing is a prime example of the Darwinian function follows form concept. A mutation that leads to a new mRNA (form) that encodes for a new functional protein (function) is likely to be retained, and this way, the genome has gradually evolved to encode for genes with multiple isoforms, thereby creating an enormously diverse transcriptome. Advances in technologies to characterize RNA populations have led to a better understanding of RNA processing in health and disease. In the heart, alternative splicing is increasingly being recognized as an important layer of post-transcriptional gene regulation. Moreover, the recent identification of several cardiac splice factors, such as RNA-binding motif protein 20 and SF3B1, not only provided important insight into the mechanisms underlying alternative splicing but also revealed how these splicing factors impact functional properties of the heart. Here, we review our current knowledge of alternative splicing in the heart, with a particular focus on the major and minor spliceosome, the factors controlling RNA splicing, and the role of alternative splicing in cardiac development and disease. © 2016 American Heart Association, Inc.

Fgfr1 regulates development through the combinatorial use of signaling proteins.

PubMed

Brewer, J Richard; Molotkov, Andrei; Mazot, Pierre; Hoch, Renée V; Soriano, Philippe

2015-09-01

Fibroblast growth factor (Fgf) signaling governs multiple processes important in development and disease. Many lines of evidence have implicated Erk1/2 signaling induced through Frs2 as the predominant effector pathway downstream from Fgf receptors (Fgfrs), but these receptors can also signal through other mechanisms. To explore the functional significance of the full range of signaling downstream from Fgfrs in mice, we engineered an allelic series of knock-in point mutations designed to disrupt Fgfr1 signaling functions individually and in combination. Analysis of each mutant indicates that Frs2 binding to Fgfr1 has the most pleiotropic functions in development but also that the receptor uses multiple proteins additively in vivo. In addition to Frs2, Crk proteins and Plcγ also contribute to Erk1/2 activation, affecting axis elongation and craniofacial and limb development and providing a biochemical mechanism for additive signaling requirements. Disruption of all known signaling functions diminished Erk1/2 and Plcγ activation but did not recapitulate the peri-implantation Fgfr1-null phenotype. This suggests that Erk1/2-independent signaling pathways are functionally important for Fgf signaling in vivo. © 2015 Brewer et al.; Published by Cold Spring Harbor Laboratory Press.

Rotor noise due to blade-turbulence interaction

NASA Astrophysics Data System (ADS)

Ishimaru, K.

1983-01-01

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)-(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function.

Concussions and Risk Within Cultural Contexts of Play.

PubMed

Torres Colón, Gabriel Alejandro; Smith, Sharia; Fucillo, Jenny

2017-06-01

Concussions are a type of traumatic injury caused by a jolting of the brain that disrupts normal brain function, and multiple concussions can lead to serious long-term health consequences. In this article, we examine the relationship between college students' understanding of concussions and their willingness to continue playing despite the possibility of sustaining multiple head injuries. We use a mixed-methods approach that includes participant observation, cultural domain analysis, and structured interviews. Our research finds that students hold a robust cognitive understanding of concussion yet discursively frame concussions as skeletomuscular injuries. More importantly, students affirm the importance of playing sports for themselves and others, so their decisions to risk multiple concussions must be understood within cultural and biocultural contexts of meaningful social play. We suggest that peoples' decision to risk multiple head injuries should be understood as a desire for meaningful social play rather than an uninformed health risk.

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2014-10-01

Unclassified b. ABSTRACT Unclassified c. THIS PAGE Unclassified Unclassified 19b. TELEPHONE NUMBER (include area code ) Standard Form 298 (Rev. 8-98...Research titled: “Passive fMRI mapping of language function for pediatric epilepsy surgery : validation using Wada, ECS, and FMAER” 2. Invited talk to...The mapping of language is important in pediatric patients who will undergo resection surgery near cortical regions essential for language function

Bottom-up synthetic biology: modular design for making artificial platelets

NASA Astrophysics Data System (ADS)

Majumder, Sagardip; Liu, Allen P.

2018-01-01

Engineering artificial cells to mimic one or multiple fundamental cell biological functions is an emerging area of synthetic biology. Reconstituting functional modules from biological components in vitro is a challenging yet an important essence of bottom-up synthetic biology. Here we describe the concept of building artificial platelets using bottom-up synthetic biology and the four functional modules that together could enable such an ambitious effort.

Self-assessment in schizophrenia: Accuracy of evaluation of cognition and everyday functioning.

PubMed

Gould, Felicia; McGuire, Laura Stone; Durand, Dante; Sabbag, Samir; Larrauri, Carlos; Patterson, Thomas L; Twamley, Elizabeth W; Harvey, Philip D

2015-09-01

Self-assessment deficits, often referred to as impaired insight or unawareness of illness, are well established in people with schizophrenia. There are multiple levels of awareness, including awareness of symptoms, functional deficits, cognitive impairments, and the ability to monitor cognitive and functional performance in an ongoing manner. The present study aimed to evaluate the comparative predictive value of each aspect of awareness on the levels of everyday functioning in people with schizophrenia. We examined multiple aspects of self-assessment of functioning in 214 people with schizophrenia. We also collected information on everyday functioning rated by high contact clinicians and examined the importance of self-assessment for the prediction of real-world functional outcomes. The relative impact of performance-based measures of cognition, functional capacity, and metacognitive performance on everyday functioning was also examined. Misestimation of ability emerged as the strongest predictor of real-world functioning and exceeded the influences of cognitive performance, functional capacity performance, and performance-based assessment of metacognitive monitoring. The relative contribution of the factors other than self-assessment varied according to which domain of everyday functioning was being examined, but, in all cases, accounted for less predictive variance. These results underscore the functional impact of misestimating one's current functioning and relative level of ability. These findings are consistent with the use of insight-focused treatments and compensatory strategies designed to increase self-awareness in multiple functional domains. (c) 2015 APA, all rights reserved).

Self Assessment in Schizophrenia: Accuracy of Evaluation of Cognition and Everyday Functioning

PubMed Central

Gould, Felicia; McGuire, Laura Stone; Durand, Dante; Sabbag, Samir; Larrauri, Carlos; Patterson, Thomas L.; Twamley, Elizabeth W.; Harvey, Philip D.

2015-01-01

Objective Self-assessment deficits, often referred to as impaired insight or unawareness of illness, are well established in people with schizophrenia. There are multiple levels of awareness, including awareness of symptoms, functional deficits, cognitive impairments, and the ability to monitor cognitive and functional performance in an ongoing manner. The present study aimed to evaluate the comparative predictive value of each aspect of awareness on the levels of everyday functioning in people with schizophrenia. Method We examined multiple aspects of self-assessment of functioning in 214 people with schizophrenia. We also collected information on everyday functioning rated by high contact clinicians and examined the importance of self-assessment for the prediction of real world functional outcomes. The relative impact of performance based measures of cognition, functional capacity, and metacognitive performance on everyday functioning was also examined. Results Misestimation of ability emerged as the strongest predictor of real world functioning and exceeded the influences of cognitive performance, functional capacity performance, and performance-based assessment of metacognitive monitoring. The relative contribution of the factors other than self-assessment varied according to which domain of everyday functioning was being examined, but in all cases, accounted for less predictive variance. Conclusions These results underscore the functional impact of misestimating one’s current functioning and relative level of ability. These findings are consistent with the use of insight-focused treatments and compensatory strategies designed to increase self-awareness in multiple functional domains. PMID:25643212

Functional sub-division of the Drosophila genome via chromatin looping: the emerging importance of CP190.

PubMed

Ahanger, Sajad H; Shouche, Yogesh S; Mishra, Rakesh K

2013-01-01

Insulators help in organizing the eukaryotic genomes into physically and functionally autonomous regions through the formation of chromatin loops. Recent findings in Drosophila and vertebrates suggest that insulators anchor multiple loci through long-distance interactions which may be mechanistically linked to insulator function. Important to such processes in Drosophila is CP190, a common co-factor of insulator complexes. CP190 is also known to associate with the nuclear matrix, components of the RNAi machinery, active promoters and borders of the repressive chromatin domains. Although CP190 plays a pivotal role in insulator function in Drosophila, vertebrates lack a probable functional equivalent of CP190 and employ CTCF as the major factor to carry out insulator function/chromatin looping. In this review, we discuss the emerging role of CP190 in tethering genome, specifically in the perspective of insulator function in Drosophila. Future studies aiming genome-wide role of CP190 in chromatin looping is likely to give important insights into the mechanism of genome organization.

Local and global bifurcations in an economic growth model with endogenous labour supply and multiplicative external habits

NASA Astrophysics Data System (ADS)

Gori, Luca; Sodini, Mauro

2014-03-01

This paper analyses the mathematical properties of an economic growth model with overlapping generations, endogenous labour supply, and multiplicative external habits. The dynamics of the economy is characterised by a two-dimensional map describing the time evolution of capital and labour supply. We show that if the relative importance of external habits in the utility function is sufficiently high, multiple (determinate or indeterminate) fixed points and poverty traps can exist. In addition, periodic or quasiperiodic behaviour and/or coexistence of attractors may occur.

Optimizing health system response to patient's needs: an argument for the importance of functioning information.

PubMed

Hopfe, Maren; Prodinger, Birgit; Bickenbach, Jerome E; Stucki, Gerold

2017-06-06

Current health systems are increasingly challenged to meet the needs of a growing number of patients living with chronic and often multiple health conditions. The primary outcome of care, it is argued, is not merely curing disease but also optimizing functioning over a person's life span. According to the World Health Organization, functioning can serve as foundation for a comprehensive picture of health and augment the biomedical perspective with a broader and more comprehensive picture of health as it plays out in people's lives. The crucial importance of information about patient's functioning for a well-performing health system, however, has yet to be sufficiently appreciated. This paper argues that functioning information is fundamental in all components of health systems and enhances the capacity of health systems to optimize patients' health and health-related needs. Beyond making sense of biomedical disease patterns, health systems can profit from using functioning information to improve interprofessional collaboration and achieve cross-cutting disease treatment outcomes. Implications for rehabilitation Functioning is a key health outcome for rehabilitation within health systems. Information on restoring, maintaining, and optimizing human functioning can strengthen health system response to patients' health and rehabilitative needs. Functioning information guides health systems to achieve cross-cutting health outcomes that respond to the needs of the growing number of individuals living with chronic and multiple health conditions. Accounting for individuals functioning helps to overcome fragmentation of care and to improve interprofessional collaboration across settings.

Role of executive functions in prospective memory in multiple sclerosis: Impact of the strength of cue-action association.

PubMed

Dagenais, Emmanuelle; Rouleau, Isabelle; Tremblay, Alexandra; Demers, Mélanie; Roger, Élaine; Jobin, Céline; Duquette, Pierre

2016-01-01

Patients diagnosed with multiple sclerosis (MS) often report prospective memory (PM) deficits. Although PM is important for daily functioning, it is not formally assessed in clinical practice. The aim of this study was to examine the role of executive functions in MS patients' PM revealed by the effect of strength of cue-action association on PM performance. Thirty-nine MS patients were compared to 18 healthy controls matched for age, gender, and education on a PM task modulating the strength of association between the cue and the intended action. Deficits in MS patients affecting both prospective and retrospective components of PM were confirmed using 2 × 2 × 2 mixed analyses of variance (ANOVAs). Among patients, multiple regression analyses revealed that the impairment was modulated by the efficiency of executive functions, whereas retrospective memory seemed to have little impact on PM performance, contrary to expectation. More specifically, results of 2 × 2 × 2 mixed-model analyses of covariance (ANCOVAs) showed that low-executive patients had more difficulty detecting and, especially, retrieving the appropriate action when the cue and the action were unrelated, whereas high-executive patients' performance seemed to be virtually unaffected by the cue-action association. Using an objective measure, these findings confirm the presence of PM deficits in MS. They also suggest that such deficits depend on executive functioning and can be reduced when automatic PM processes are engaged through semantic cue-action association. They underscore the importance of assessing PM in clinical settings through a cognitive evaluation and offer an interesting avenue for rehabilitation.

Epigenomics and the concept of degeneracy in biological systems

PubMed Central

Mason, Paul H.; Barron, Andrew B.

2014-01-01

Researchers in the field of epigenomics are developing more nuanced understandings of biological complexity, and exploring the multiple pathways that lead to phenotypic expression. The concept of degeneracy—referring to the multiple pathways that a system recruits to achieve functional plasticity—is an important conceptual accompaniment to the growing body of knowledge in epigenomics. Distinct from degradation, redundancy and dilapidation; degeneracy refers to the plasticity of traits whose function overlaps in some environments, but diverges in others. While a redundant system is composed of repeated identical elements performing the same function, a degenerate system is composed of different elements performing similar or overlapping functions. Here, we describe the degenerate structure of gene regulatory systems from the basic genetic code to flexible epigenomic modifications, and discuss how these structural features have contributed to organism complexity, robustness, plasticity and evolvability. PMID:24335757

A model for making project funding decisions at the National Cancer Institute.

PubMed

Hall, N G; Hershey, J C; Kessler, L G; Stotts, R C

1992-01-01

This paper describes the development of a model for making project funding decisions at The National Cancer Institute (NCI). The American Stop Smoking Intervention Study (ASSIST) is a multiple-year, multiple-site demonstration project, aimed at reducing smoking prevalence. The initial request for ASSIST proposals was answered by about twice as many states as could be funded. Scientific peer review of the proposals was the primary criterion used for funding decisions. However, a modified Delphi process made explicit several criteria of secondary importance. A structured questionnaire identified the relative importance of these secondary criteria, some of which we incorporated into a composite preference function. We modeled the proposal funding decision as a zero-one program, and adjusted the preference function and available budget parametrically to generate many suitable outcomes. The actual funding decision, identified by our model, offers significant advantages over manually generated solutions found by experts at NCI.

Multiple Applications of Alamar Blue as an Indicator of Metabolic Function and Cellular Health in Cell Viability Bioassays

PubMed Central

Rampersad, Sephra N.

2012-01-01

Accurate prediction of the adverse effects of test compounds on living systems, detection of toxic thresholds, and expansion of experimental data sets to include multiple toxicity end-point analysis are required for any robust screening regime. Alamar Blue is an important redox indicator that is used to evaluate metabolic function and cellular health. The Alamar Blue bioassay has been utilized over the past 50 years to assess cell viability and cytotoxicity in a range of biological and environmental systems and in a number of cell types including bacteria, yeast, fungi, protozoa and cultured mammalian and piscine cells. It offers several advantages over other metabolic indicators and other cytotoxicity assays. However, as with any bioassay, suitability must be determined for each application and cell model. This review seeks to highlight many of the important considerations involved in assay use and design in addition to the potential pitfalls. PMID:23112716

Comparison Between Polynomial, Euler Beta-Function and Expo-Rational B-Spline Bases

NASA Astrophysics Data System (ADS)

Kristoffersen, Arnt R.; Dechevsky, Lubomir T.; Laksa˚, Arne; Bang, Børre

2011-12-01

Euler Beta-function B-splines (BFBS) are the practically most important instance of generalized expo-rational B-splines (GERBS) which are not true expo-rational B-splines (ERBS). BFBS do not enjoy the full range of the superproperties of ERBS but, while ERBS are special functions computable by a very rapidly converging yet approximate numerical quadrature algorithms, BFBS are explicitly computable piecewise polynomial (for integer multiplicities), similar to classical Schoenberg B-splines. In the present communication we define, compute and visualize for the first time all possible BFBS of degree up to 3 which provide Hermite interpolation in three consecutive knots of multiplicity up to 3, i.e., the function is being interpolated together with its derivatives of order up to 2. We compare the BFBS obtained for different degrees and multiplicities among themselves and versus the classical Schoenberg polynomial B-splines and the true ERBS for the considered knots. The results of the graphical comparison are discussed from analytical point of view. For the numerical computation and visualization of the new B-splines we have used Maple 12.

Multiple heteroatom substitution to graphene nanoribbon

PubMed Central

Meyer, Ernst

2018-01-01

Substituting heteroatoms into nanostructured graphene elements, such as graphene nanoribbons, offers the possibility for atomic engineering of electronic properties. To characterize these substitutions, functionalized atomic force microscopy (AFM)—a tool to directly resolve chemical structures—is one of the most promising tools, yet the chemical analysis of heteroatoms has been rarely performed. We synthesized multiple heteroatom-substituted graphene nanoribbons and showed that AFM can directly resolve elemental differences and can be correlated to the van der Waals radii, as well as the modulated local electron density caused by the substitution. This elemental-sensitive measurement takes an important step in the analysis of functionalized two-dimensional carbon materials. PMID:29662955

Detecting multiple outliers in linear functional relationship model for circular variables using clustering technique

NASA Astrophysics Data System (ADS)

Mokhtar, Nurkhairany Amyra; Zubairi, Yong Zulina; Hussin, Abdul Ghapor

2017-05-01

Outlier detection has been used extensively in data analysis to detect anomalous observation in data and has important application in fraud detection and robust analysis. In this paper, we propose a method in detecting multiple outliers for circular variables in linear functional relationship model. Using the residual values of the Caires and Wyatt model, we applied the hierarchical clustering procedure. With the use of tree diagram, we illustrate the graphical approach of the detection of outlier. A simulation study is done to verify the accuracy of the proposed method. Also, an illustration to a real data set is given to show its practical applicability.

Biodiversity in the City: Fundamental Questions for Understanding the Ecology of Urban Green Spaces for Biodiversity Conservation

Treesearch

Christopher A. Lepczyk; Myla F. J. Aronson; Karl L. Evans; Mark A. Goddard; Susannah B. Lerman; J. Scott MacIvor

2017-01-01

As urban areas expand, understanding how ecological processes function in cities has become increasingly important for conserving biodiversity. Urban green spaces are critical habitats to support biodiversity, but we still have a limited understanding of their ecology and how they function to conserve biodiversity at local and landscape scales across multiple taxa....

Further studies of crania from ancient northern Africa: an analysis of crania from first dynasty Egyptian tombs, using discriminant functions.

PubMed

Keita, S O

1992-03-01

An analysis of First Dynasty crania from Abydos was undertaken using multiple discriminant functions. The results demonstrate greater affinity with Upper Nile Valley patterns, but also suggest change from earlier craniometric trends. Gene flow and movement of northern officials to the important southern city may explain the findings.

XAFS Debye-Waller Factors Temperature-Dependent Expressions for Fe+2-Porphyrin Complexes

NASA Astrophysics Data System (ADS)

Dimakis, Nicholas; Bunker, Grant

2007-02-01

We present an efficient and accurate method for directly calculating single and multiple scattering X-ray absorption fine structure (XAFS) thermal Debye-Waller factors for Fe+2 -porphiryn complexes. The number of multiple scattering Debye-Waller factors on metal porphyrin centers exceeds the number of available parameters that XAFS experimental data can support during fitting with simulated spectra. Using the Density Functional Theory (DFT) under the hybrid functional of X3LYP, phonon normal mode spectrum properties are used to express the mean square variation of the half-scattering path length for a Fe+2 -porphiryn complex as a function of temperature for the most important single and multiple scattering paths of the complex thus virtually eliminating them from the fitting procedure. Modeled calculations are compared with corresponding values obtained from DFT-built and optimized Fe+2 -porphyrin bis-histidine structure as well as from experimental XAFS spectra previously reported. An excellent agreement between calculated and reference Debye-Waller factors for Fe+2-porphyrins is obtained.

Resilience and stability of a pelagic marine ecosystem

PubMed Central

Lindegren, Martin; Checkley, David M.; Ohman, Mark D.; Koslow, J. Anthony; Goericke, Ralf

2016-01-01

The accelerating loss of biodiversity and ecosystem services worldwide has accentuated a long-standing debate on the role of diversity in stabilizing ecological communities and has given rise to a field of research on biodiversity and ecosystem functioning (BEF). Although broad consensus has been reached regarding the positive BEF relationship, a number of important challenges remain unanswered. These primarily concern the underlying mechanisms by which diversity increases resilience and community stability, particularly the relative importance of statistical averaging and functional complementarity. Our understanding of these mechanisms relies heavily on theoretical and experimental studies, yet the degree to which theory adequately explains the dynamics and stability of natural ecosystems is largely unknown, especially in marine ecosystems. Using modelling and a unique 60-year dataset covering multiple trophic levels, we show that the pronounced multi-decadal variability of the Southern California Current System (SCCS) does not represent fundamental changes in ecosystem functioning, but a linear response to key environmental drivers channelled through bottom-up and physical control. Furthermore, we show strong temporal asynchrony between key species or functional groups within multiple trophic levels caused by opposite responses to these drivers. We argue that functional complementarity is the primary mechanism reducing community variability and promoting resilience and stability in the SCCS. PMID:26763697

The importance of biodiversity and dominance for multiple ecosystem functions in a human-modified tropical landscape.

PubMed

Lohbeck, Madelon; Bongers, Frans; Martinez-Ramos, Miguel; Poorter, Lourens

2016-10-01

Many studies suggest that biodiversity may be particularly important for ecosystem multifunctionality, because different species with different traits can contribute to different functions. Support, however, comes mostly from experimental studies conducted at small spatial scales in low-diversity systems. Here, we test whether different species contribute to different ecosystem functions that are important for carbon cycling in a high-diversity human-modified tropical forest landscape in Southern Mexico. We quantified aboveground standing biomass, primary productivity, litter production, and wood decomposition at the landscape level, and evaluated the extent to which tree species contribute to these ecosystem functions. We used simulations to tease apart the effects of species richness, species dominance and species functional traits on ecosystem functions. We found that dominance was more important than species traits in determining a species' contribution to ecosystem functions. As a consequence of the high dominance in human-modified landscapes, the same small subset of species mattered across different functions. In human-modified landscapes in the tropics, biodiversity may play a limited role for ecosystem multifunctionality due to the potentially large effect of species dominance on biogeochemical functions. However, given the spatial and temporal turnover in species dominance, biodiversity may be critically important for the maintenance and resilience of ecosystem functions. © 2016 The Authors. Ecology, published by Wiley Periodicals, Inc., on behalf of the Ecological Society of America.

Lifestyle and Mental Health

ERIC Educational Resources Information Center

Walsh, Roger

2011-01-01

Mental health professionals have significantly underestimated the importance of lifestyle factors (a) as contributors to and treatments for multiple psychopathologies, (b) for fostering individual and social well-being, and (c) for preserving and optimizing cognitive function. Consequently, therapeutic lifestyle changes (TLCs) are underutilized…

[The possibility of using music therapy in neurology on the example of multiple sclerosis].

PubMed

Boiko, E A; Ivanchuk, E V; Gunchenko, M M; Batysheva, T T

2016-01-01

Currently music therapy plays an important role in the drug-free treatment and rehabilitation of children and adults with acute and chronic neurological and somatic diseases including demyelinating diseases. Existing studies show the effectiveness of music therapy in the improvement of social skills, cognitive function and sleep as well as in the reduction in the severity of depression, anxiety and pain in patients with multiple sclerosis.

Does Distress Tolerance Moderate the Impact of Major Life Events on Psychosocial Variables and Behaviors Important in the Management of HIV?

ERIC Educational Resources Information Center

O'Cleirigh, Conall; Ironson, Gail; Smits, Jasper A. J.

2007-01-01

Living with HIV involves management of multiple stressful disease-related and other life events. Distress tolerance may provide a functional, individual-based context for qualifying the established relationships between major life events and psychosocial variables important in the management of HIV. The present study provided a preliminary test of…

Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

PubMed Central

Xu, Jianfeng; Lan, Yueheng

2015-01-01

Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

The role of bile acids in metabolic regulation.

PubMed

Vítek, Libor; Haluzík, Martin

2016-03-01

Bile acids (BA), long believed to only have lipid-digestive functions, have emerged as novel metabolic modulators. They have important endocrine effects through multiple cytoplasmic as well as nuclear receptors in various organs and tissues. BA affect multiple functions to control energy homeostasis, as well as glucose and lipid metabolism, predominantly by activating the nuclear farnesoid X receptor and the cytoplasmic G protein-coupled BA receptor TGR5 in a variety of tissues. However, BA also are aimed at many other cellular targets in a wide array of organs and cell compartments. Their role in the pathogenesis of diabetes, obesity and other 'diseases of civilization' becomes even more clear. They also interact with the gut microbiome, with important clinical implications, further extending the complexity of their biological functions. Therefore, it is not surprising that BA metabolism is substantially modulated by bariatric surgery, a phenomenon contributing favorably to the therapeutic effects of these surgical procedures. Based on these data, several therapeutic approaches to ameliorate obesity and diabetes have been proposed to affect the cellular targets of BA. © 2016 Society for Endocrinology.

The Popeye domain containing protein family--A novel class of cAMP effectors with important functions in multiple tissues.

PubMed

Schindler, Roland F R; Brand, Thomas

2016-01-01

Popeye domain containing (Popdc) proteins are a unique family, which combine several different properties and functions in a surprisingly complex fashion. They are expressed in multiple tissues and cell types, present in several subcellular compartments, interact with different classes of proteins, and are associated with a variety of physiological and pathophysiological processes. Moreover, Popdc proteins bind the second messenger cAMP with high affinity and it is thought that they act as a novel class of cAMP effector proteins. Here, we will review the most important findings about the Popdc family, which accumulated since its discovery about 15 years ago. We will be focussing on Popdc protein interaction and function in striated muscle tissue. However, as a full picture only emerges if all aspects are taken into account, we will also describe what is currently known about the role of Popdc proteins in epithelial cells and in various types of cancer, and discuss these findings with regard to their relevance for cardiac and skeletal muscle. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Structure and functioning of dryland ecosystems in a changing world.

PubMed

Maestre, Fernando T; Eldridge, David J; Soliveres, Santiago; Kéfi, Sonia; Delgado-Baquerizo, Manuel; Bowker, Matthew A; García-Palacios, Pablo; Gaitán, Juan; Gallardo, Antonio; Lázaro, Roberto; Berdugo, Miguel

2016-11-01

Understanding how drylands respond to ongoing environmental change is extremely important for global sustainability. Here we review how biotic attributes, climate, grazing pressure, land cover change and nitrogen deposition affect the functioning of drylands at multiple spatial scales. Our synthesis highlights the importance of biotic attributes (e.g. species richness) in maintaining fundamental ecosystem processes such as primary productivity, illustrate how N deposition and grazing pressure are impacting ecosystem functioning in drylands worldwide, and highlight the importance of the traits of woody species as drivers of their expansion in former grasslands. We also emphasize the role of attributes such as species richness and abundance in controlling the responses of ecosystem functioning to climate change. This knowledge is essential to guide conservation and restoration efforts in drylands, as biotic attributes can be actively managed at the local scale to increase ecosystem resilience to global change.

Structure and functioning of dryland ecosystems in a changing world

PubMed Central

Maestre, Fernando T.; Eldridge, David J.; Soliveres, Santiago; Kéfi, Sonia; Delgado-Baquerizo, Manuel; Bowker, Matthew A.; García-Palacios, Pablo; Gaitán, Juan; Gallardo, Antonio; Lázaro, Roberto; Berdugo, Miguel

2017-01-01

Understanding how drylands respond to ongoing environmental change is extremely important for global sustainability. Here we review how biotic attributes, climate, grazing pressure, land cover change and nitrogen deposition affect the functioning of drylands at multiple spatial scales. Our synthesis highlights the importance of biotic attributes (e.g. species richness) in maintaining fundamental ecosystem processes such as primary productivity, illustrate how N deposition and grazing pressure are impacting ecosystem functioning in drylands worldwide, and highlight the importance of the traits of woody species as drivers of their expansion in former grasslands. We also emphasize the role of attributes such as species richness and abundance in controlling the responses of ecosystem functioning to climate change. This knowledge is essential to guide conservation and restoration efforts in drylands, as biotic attributes can be actively managed at the local scale to increase ecosystem resilience to global change. PMID:28239303

Rising tides, cumulative impacts and cascading changes to estuarine ecosystem functions.

PubMed

O'Meara, Theresa A; Hillman, Jenny R; Thrush, Simon F

2017-08-31

In coastal ecosystems, climate change affects multiple environmental factors, yet most predictive models are based on simple cause-and-effect relationships. Multiple stressor scenarios are difficult to predict because they can create a ripple effect through networked ecosystem functions. Estuarine ecosystem function relies on an interconnected network of physical and biological processes. Estuarine habitats play critical roles in service provision and represent global hotspots for organic matter processing, nutrient cycling and primary production. Within these systems, we predicted functional changes in the impacts of land-based stressors, mediated by changing light climate and sediment permeability. Our in-situ field experiment manipulated sea level, nutrient supply, and mud content. We used these stressors to determine how interacting environmental stressors influence ecosystem function and compared results with data collected along elevation gradients to substitute space for time. We show non-linear, multi-stressor effects deconstruct networks governing ecosystem function. Sea level rise altered nutrient processing and impacted broader estuarine services ameliorating nutrient and sediment pollution. Our experiment demonstrates how the relationships between nutrient processing and biological/physical controls degrade with environmental stress. Our results emphasise the importance of moving beyond simple physically-forced relationships to assess consequences of climate change in the context of ecosystem interactions and multiple stressors.

Ligand-guided optimization of CXCR4 homology models for virtual screening using a multiple chemotype approach

NASA Astrophysics Data System (ADS)

Neves, Marco A. C.; Simões, Sérgio; Sá e Melo, M. Luisa

2010-12-01

CXCR4 is a G-protein coupled receptor for CXCL12 that plays an important role in human immunodeficiency virus infection, cancer growth and metastasization, immune cell trafficking and WHIM syndrome. In the absence of an X-ray crystal structure, theoretical modeling of the CXCR4 receptor remains an important tool for structure-function analysis and to guide the discovery of new antagonists with potential clinical use. In this study, the combination of experimental data and molecular modeling approaches allowed the development of optimized ligand-receptor models useful for elucidation of the molecular determinants of small molecule binding and functional antagonism. The ligand-guided homology modeling approach used in this study explicitly re-shaped the CXCR4 binding pocket in order to improve discrimination between known CXCR4 antagonists and random decoys. Refinement based on multiple test-sets with small compounds from single chemotypes provided the best early enrichment performance. These results provide an important tool for structure-based drug design and virtual ligand screening of new CXCR4 antagonists.

Alteration of Multiple Cell Membrane Functions in L-6 Myoblasts by T-2 Toxin: An Important Mechanism of Action.

DTIC Science & Technology

1986-06-04

menbrane functions. All are in a range that would in turn be expected to alter other cell functions. Intracellular LEH was reduced 10 min after T-2... Plasma amino F-id changes in guinea pigs injected with T-2 rnycotoxin. Fed. Proc. 42, 625. 20 1111" ll p J IIIý f%𔃻 11 IC IA 114 WEAVER, G.A., MW1•Z, H.J

Vision and vision-related outcome measures in multiple sclerosis

PubMed Central

Balcer, Laura J.; Miller, David H.; Reingold, Stephen C.

2015-01-01

Visual impairment is a key manifestation of multiple sclerosis. Acute optic neuritis is a common, often presenting manifestation, but visual deficits and structural loss of retinal axonal and neuronal integrity can occur even without a history of optic neuritis. Interest in vision in multiple sclerosis is growing, partially in response to the development of sensitive visual function tests, structural markers such as optical coherence tomography and magnetic resonance imaging, and quality of life measures that give clinical meaning to the structure-function correlations that are unique to the afferent visual pathway. Abnormal eye movements also are common in multiple sclerosis, but quantitative assessment methods that can be applied in practice and clinical trials are not readily available. We summarize here a comprehensive literature search and the discussion at a recent international meeting of investigators involved in the development and study of visual outcomes in multiple sclerosis, which had, as its overriding goals, to review the state of the field and identify areas for future research. We review data and principles to help us understand the importance of vision as a model for outcomes assessment in clinical practice and therapeutic trials in multiple sclerosis. PMID:25433914

Characterizing Individual Differences in Functional Connectivity Using Dual-Regression and Seed-Based Approaches

PubMed Central

Smith, David V.; Utevsky, Amanda V.; Bland, Amy R.; Clement, Nathan; Clithero, John A.; Harsch, Anne E. W.; Carter, R. McKell; Huettel, Scott A.

2014-01-01

A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent components analysis (ICA). We estimated voxelwise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust—yet frequently ignored—neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. PMID:24662574

The relation between circadian asynchrony, functional redundancy, and trophic performance in tropical ant communities.

PubMed

Houadria, Mickal; Blüthgen, Nico; Salas-Lopez, Alex; Schmitt, Mona-Isabel; Arndt, Johanna; Schneider, Eric; Orivel, Jérôme; Menzel, Florian

2016-01-01

The diversity-stability relationship has been under intense scrutiny for the past decades, and temporal asynchrony is recognized as an important aspect of ecosystem stability. In contrast to relatively well-studied interannual and seasonal asynchrony, few studies investigate the role of circadian cycles for ecosystem stability. Here, we studied multifunctional redundancy of diurnal and nocturnal ant communities in four tropical rain forest sites. We analyzed how it was influenced by species richness, functional performance, and circadian asynchrony. In two neotropical sites, species richness and functional redundancy were lower at night. In contrast, these parameters did not differ in the two paleotropical sites we studied. Circadian asynchrony between species was pronounced in the neotropical sites, and increased circadian functional redundancy. In general, species richness positively affected functional redundancy, but the effect size depended on the temporal and spatial breadth of the species with highest functional performance. Our analysis shows that high levels of trophic performance were only reached through the presence of such high-performing species, but not by even contributions of multiple, less-efficient species. Thus, these species can increase current functional performance, but reduce overall functional redundancy. Our study highlights that diurnal and nocturnal ecosystem properties of the very same habitat can markedly differ in terms of species richness and functional redundancy. Consequently, like the need to study multiple ecosystem functions, multiple periods of the circadian cycle need to be assessed in order to fully understand the diversity-stability relationship in an ecosystem.

[Advances in the study of neuroendocrinological regulation of kisspeptin in fish reproduction].

PubMed

Zhuo, Qi

2013-10-01

Kisspeptin, a key factor in the neuroendocrinological regulation of animal reproduction, is a peptide product encoded by kiss genes, which act as the natural ligand of GPR54. Over the last decade, multiple functional molecular forms of kisspeptin have been found in vertebrate species. In fish, the major molecular structural form is kisspeptin-10. The kisspeptin/GPR54 system has multiple important functions in reproduction. This review provides an overview of our current knowledge on kisspeptin and its role in regulating fish reproductive, including the distribution and location of kisspeptin neurons in the brain, the molecular polymorphism of fish kisspeptin, functional diversity, the molecular mechanism of fish reproductive regulation, and the molecular evolution of kisspeptin as well as the co-regulation of fish reproduction by kisspeptin and other functional molecules. Perspectives on the future of kisspeptin regulation in fish reproduction are also highlighted.

Teaching individuals with intellectual disability to email across multiple device platforms.

PubMed

Cihak, David F; McMahon, Donald; Smith, Cate C; Wright, Rachel; Gibbons, Melinda M

2014-11-20

The purpose of this study was to examine the use of email by people with intellectual disability across multiple technological devices or platforms. Four individuals with intellectual disability participated in this study. Participants were taught how to access and send an email on a Windows desktop computer, laptop, and an iPad tablet device. Results indicated a functional relation. All participants acquired and generalized sending and receiving an email from multiple platforms. Conclusions are discussed about the importance of empowering people with intellectual disability by providing multiple means of expression, including the ability to communicate effectively using a variety of devices. Copyright © 2014 Elsevier Ltd. All rights reserved.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication

PubMed Central

Herod, Morgan R.; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C.; Verdaguer, Nuria; Rowlands, David J.

2016-01-01

ABSTRACT The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. IMPORTANCE Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. PMID:27194768

Intraguild predation reduces redundancy of predator species in multiple predator assemblage.

PubMed

Griffen, Blaine D; Byers, James E

2006-07-01

1. Interference between predator species frequently decreases predation rates, lowering the risk of predation for shared prey. However, such interference can also occur between conspecific predators. 2. Therefore, to understand the importance of predator biodiversity and the degree that predator species can be considered functionally interchangeable, we determined the degree of additivity and redundancy of predators in multiple- and single-species combinations. 3. We show that interference between two invasive species of predatory crabs, Carcinus maenas and Hemigrapsus sanguineus, reduced the risk of predation for shared amphipod prey, and had redundant per capita effects in most multiple- and single-species predator combinations. 4. However, when predator combinations with the potential for intraguild predation were examined, predator interference increased and predator redundancy decreased. 5. Our study indicates that trophic structure is important in determining how the effects of predator species combine and demonstrates the utility of determining the redundancy, as well as the additivity, of multiple predator species.

Sparse representation of whole-brain fMRI signals for identification of functional networks.

PubMed

Lv, Jinglei; Jiang, Xi; Li, Xiang; Zhu, Dajiang; Chen, Hanbo; Zhang, Tuo; Zhang, Shu; Hu, Xintao; Han, Junwei; Huang, Heng; Zhang, Jing; Guo, Lei; Liu, Tianming

2015-02-01

There have been several recent studies that used sparse representation for fMRI signal analysis and activation detection based on the assumption that each voxel's fMRI signal is linearly composed of sparse components. Previous studies have employed sparse coding to model functional networks in various modalities and scales. These prior contributions inspired the exploration of whether/how sparse representation can be used to identify functional networks in a voxel-wise way and on the whole brain scale. This paper presents a novel, alternative methodology of identifying multiple functional networks via sparse representation of whole-brain task-based fMRI signals. Our basic idea is that all fMRI signals within the whole brain of one subject are aggregated into a big data matrix, which is then factorized into an over-complete dictionary basis matrix and a reference weight matrix via an effective online dictionary learning algorithm. Our extensive experimental results have shown that this novel methodology can uncover multiple functional networks that can be well characterized and interpreted in spatial, temporal and frequency domains based on current brain science knowledge. Importantly, these well-characterized functional network components are quite reproducible in different brains. In general, our methods offer a novel, effective and unified solution to multiple fMRI data analysis tasks including activation detection, de-activation detection, and functional network identification. Copyright © 2014 Elsevier B.V. All rights reserved.

Rotor Noise due to Blade-Turbulence Interaction.

NASA Astrophysics Data System (ADS)

Ishimaru, Kiyoto

The time-averaged intensity density function of the acoustic radiation from rotating blades is derived by replacing blades with rotating dipoles. This derivation is done under the following turbulent inflow conditions: turbulent ingestion with no inlet strut wakes, inflow turbulence elongation and contraction with no inlet strut wakes, and inlet strut wakes. Dimensional analysis reveals two non-dimensional parameters which play important roles in generating the blade-passing frequency tone and its multiples. The elongation and contraction of inflow turbulence has a strong effect on the generation of the blade-passing frequency tone and its multiples. Increasing the number of rotor blades widens the peak at the blade-passing frequency and its multiples. Increasing the rotational speed widens the peak under the condition that the non-dimensional parameter involving the rotational speed is fixed. The number of struts and blades should be chosen so that (the least common multiple of them)(.)(rotational speed) is in the cutoff range of Sears' function, in order to minimize the effect of the mean flow deficit on the time averaged intensity density function. The acoustic intensity density function is not necessarily stationary even if the inflow turbulence is homogeneous and isotropic. The time variation of the propagation path due to the rotation should be considered in the computation of the intensity density function; for instance, in the present rotor specification, the rotor radius is about 0.3 m and the rotational speed Mach number is about 0.2.

Episodic memory in former professional football players with a history of concussion: an event-related functional neuroimaging study.

PubMed

Ford, Jaclyn H; Giovanello, Kelly S; Guskiewicz, Kevin M

2013-10-15

Previous research has demonstrated that sport-related concussions can have short-term effects on cognitive processes, but the long-term consequences are less understood and warrant more research. This study was the first to use event-related functional magnetic resonance imaging (fMRI) to examine long-term differences in neural activity during memory tasks in former athletes who have sustained multiple sport-related concussions. In an event-related fMRI study, former football players reporting multiple sport-related concussions (i.e., three or more) were compared with players who reported fewer than three concussions during a memory paradigm examining item memory (i.e., memory for the particular elements of an event) and relational memory (i.e., memory for the relationships between elements). Behaviorally, we observed that concussion history did not significantly affect behavioral performance, because persons in the low and high concussion groups had equivalent performance on both memory tasks, and in addition, that concussion history was not associated with any behavioral memory measures. Despite demonstrating equivalent behavioral performance, the two groups of former players demonstrated different neural recruitment patterns during relational memory retrieval, suggesting that multiple concussions may be associated with functional inefficiencies in the relational memory network. In addition, the number of previous concussions significantly correlated with functional activity in a number of brain regions, including the medial temporal lobe and inferior parietal lobe. Our results provide important insights in understanding the long-term functional consequences of sustaining multiple sports-related concussions.

Eigenvector decomposition of full-spectrum x-ray computed tomography.

PubMed

Gonzales, Brian J; Lalush, David S

2012-03-07

Energy-discriminated x-ray computed tomography (CT) data were projected onto a set of basis functions to suppress the noise in filtered back-projection (FBP) reconstructions. The x-ray CT data were acquired using a novel x-ray system which incorporated a single-pixel photon-counting x-ray detector to measure the x-ray spectrum for each projection ray. A matrix of the spectral response of different materials was decomposed using eigenvalue decomposition to form the basis functions. Projection of FBP onto basis functions created a de facto image segmentation of multiple contrast agents. Final reconstructions showed significant noise suppression while preserving important energy-axis data. The noise suppression was demonstrated by a marked improvement in the signal-to-noise ratio (SNR) along the energy axis for multiple regions of interest in the reconstructed images. Basis functions used on a more coarsely sampled energy axis still showed an improved SNR. We conclude that the noise-resolution trade off along the energy axis was significantly improved using the eigenvalue decomposition basis functions.

Consistent effects of biodiversity loss on multifunctionality across contrasting ecosystems.

PubMed

Fanin, Nicolas; Gundale, Michael J; Farrell, Mark; Ciobanu, Marcel; Baldock, Jeff A; Nilsson, Marie-Charlotte; Kardol, Paul; Wardle, David A

2018-02-01

Understanding how loss of biodiversity affects ecosystem functioning, and thus the delivery of ecosystem goods and services, has become increasingly necessary in a changing world. Considerable recent attention has focused on predicting how biodiversity loss simultaneously impacts multiple ecosystem functions (that is, ecosystem multifunctionality), but the ways in which these effects vary across ecosystems remain unclear. Here, we report the results of two 19-year plant diversity manipulation experiments, each established across a strong environmental gradient. Although the effects of plant and associated fungal diversity loss on individual functions frequently differed among ecosystems, the consequences of biodiversity loss for multifunctionality were relatively invariant. However, the context-dependency of biodiversity effects also worked in opposing directions for different individual functions, meaning that similar multifunctionality values across contrasting ecosystems could potentially mask important differences in the effects of biodiversity on functioning among ecosystems. Our findings highlight that an understanding of the relative contribution of species or functional groups to individual ecosystem functions among contrasting ecosystems and their interactions (that is, complementarity versus competition) is critical for guiding management efforts aimed at maintaining ecosystem multifunctionality and the delivery of multiple ecosystem services.

Conservation of tubulin-binding sequences in TRPV1 throughout evolution.

PubMed

Sardar, Puspendu; Kumar, Abhishek; Bhandari, Anita; Goswami, Chandan

2012-01-01

Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. Using statistical and bioinformatics tools, our analysis reveals that TRPV1 has evolved about ∼420 million years ago (MYA). Our analysis reveals that specific regions, domains and motifs of TRPV1 has gone through different selection pressure and thus have different levels of conservation. We found that among all, TRP box is the most conserved and thus have functional significance. Our results also indicate that the tubulin binding sequences (TBS) have evolutionary significance as these stretch sequences are more conserved than many other essential regions of TRPV1. The overall distribution of positively charged residues within the TBS motifs is conserved throughout evolution. In silico analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function. Our analysis identifies the regions of TRPV1, which are important for structure-function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy.

From a meso- to micro-scale connectome: array tomography and mGRASP

PubMed Central

Rah, Jong-Cheol; Feng, Linqing; Druckmann, Shaul; Lee, Hojin; Kim, Jinhyun

2015-01-01

Mapping mammalian synaptic connectivity has long been an important goal of neuroscience because knowing how neurons and brain areas are connected underpins an understanding of brain function. Meeting this goal requires advanced techniques with single synapse resolution and large-scale capacity, especially at multiple scales tethering the meso- and micro-scale connectome. Among several advanced LM-based connectome technologies, Array Tomography (AT) and mammalian GFP-Reconstitution Across Synaptic Partners (mGRASP) can provide relatively high-throughput mapping synaptic connectivity at multiple scales. AT- and mGRASP-assisted circuit mapping (ATing and mGRASPing), combined with techniques such as retrograde virus, brain clearing techniques, and activity indicators will help unlock the secrets of complex neural circuits. Here, we discuss these useful new tools to enable mapping of brain circuits at multiple scales, some functional implications of spatial synaptic distribution, and future challenges and directions of these endeavors. PMID:26089781

Epithelial Integrity Is Maintained by a Matriptase-Dependent Proteolytic Pathway

PubMed Central

List, Karin; Kosa, Peter; Szabo, Roman; Bey, Alexandra L.; Wang, Chao Becky; Molinolo, Alfredo; Bugge, Thomas H.

2009-01-01

A pericellular proteolytic pathway initiated by the transmembrane serine protease matriptase plays a critical role in the terminal differentiation of epidermal tissues. Matriptase is constitutively expressed in multiple other epithelia, suggesting a putative role of this membrane serine protease in general epithelial homeostasis. Here we generated mice with conditional deletion of the St14 gene, encoding matriptase, and show that matriptase indeed is essential for the maintenance of multiple types of epithelia in the mouse. Thus, embryonic or postnatal ablation of St14 in epithelial tissues of diverse origin and function caused severe organ dysfunction, which was often associated with increased permeability, loss of tight junction function, mislocation of tight junction-associated proteins, and generalized epithelial demise. The study reveals that the homeostasis of multiple simple and stratified epithelia is matriptase-dependent, and provides an important animal model for the exploration of this membrane serine protease in a range of physiological and pathological processes. PMID:19717635

A Class of Manifold Regularized Multiplicative Update Algorithms for Image Clustering.

PubMed

Yang, Shangming; Yi, Zhang; He, Xiaofei; Li, Xuelong

2015-12-01

Multiplicative update algorithms are important tools for information retrieval, image processing, and pattern recognition. However, when the graph regularization is added to the cost function, different classes of sample data may be mapped to the same subspace, which leads to the increase of data clustering error rate. In this paper, an improved nonnegative matrix factorization (NMF) cost function is introduced. Based on the cost function, a class of novel graph regularized NMF algorithms is developed, which results in a class of extended multiplicative update algorithms with manifold structure regularization. Analysis shows that in the learning, the proposed algorithms can efficiently minimize the rank of the data representation matrix. Theoretical results presented in this paper are confirmed by simulations. For different initializations and data sets, variation curves of cost functions and decomposition data are presented to show the convergence features of the proposed update rules. Basis images, reconstructed images, and clustering results are utilized to present the efficiency of the new algorithms. Last, the clustering accuracies of different algorithms are also investigated, which shows that the proposed algorithms can achieve state-of-the-art performance in applications of image clustering.

The multiple-function multi-input/multi-output digital controller system for the AFW wind-tunnel model

NASA Technical Reports Server (NTRS)

Hoadley, Sherwood T.; Mcgraw, Sandra M.

1992-01-01

A real time multiple-function digital controller system was developed for the Active Flexible Wing (AFW) Program. The digital controller system (DCS) allowed simultaneous execution of two control laws: flutter suppression and either roll trim or a rolling maneuver load control. The DCS operated within, but independently of, a slower host operating system environment, at regulated speeds up to 200 Hz. It also coordinated the acquisition, storage, and transfer of data for near real time controller performance evaluation and both open- and closed-loop plant estimation. It synchronized the operation of four different processing units, allowing flexibility in the number, form, functionality, and order of control laws, and variability in the selection of the sensors and actuators employed. Most importantly, the DCS allowed for the successful demonstration of active flutter suppression to conditions approximately 26 percent (in dynamic pressure) above the open-loop boundary in cases when the model was fixed in roll and up to 23 percent when it was free to roll. Aggressive roll maneuvers with load control were achieved above the flutter boundary. The purpose here is to present the development, validation, and wind tunnel testing of this multiple-function digital controller system.

Selection of multiple umbrella species for functional and taxonomic diversity to represent urban biodiversity.

PubMed

Sattler, T; Pezzatti, G B; Nobis, M P; Obrist, M K; Roth, T; Moretti, M

2014-04-01

Surrogates, such as umbrella species, are commonly used to reduce the complexity of quantifying biodiversity for conservation purposes. The presence of umbrella species is often indicative of high taxonomic diversity; however, functional diversity is now recognized as an important metric for biodiversity and thus should be considered when choosing umbrella species. We identified umbrella species associated with high taxonomic and functional biodiversity in urban areas in Switzerland. We analyzed 39,752 individuals of 574 animal species from 96 study plots and 1397 presences of 262 plant species from 58 plots. Thirty-one biodiversity measures of 7 taxonomic groups (plants, spiders, bees, ground beetles, lady bugs, weevils and birds) were included in within- and across-taxa analyses. Sixteen measures were taxonomical (species richness and species diversity), whereas 15 were functional (species traits including mobility, resource use, and reproduction). We used indicator value analysis to identify umbrella species associated with single or multiple biodiversity measures. Many umbrella species were indicators of high biodiversity within their own taxonomic group (from 33.3% in weevils to 93.8% in birds), to a lesser extent they were indicators across taxa. Principal component analysis revealed that umbrella species for multiple measures of biodiversity represented different aspects of biodiversity, especially with respect to measures of taxonomic and functional diversity. Thus, even umbrella species for multiple measures of biodiversity were complementary in the biodiversity aspects they represented. Thus, the choice of umbrella species based solely on taxonomic diversity is questionable and may not represent biodiversity comprehensively. Our results suggest that, depending on conservation priorities, managers should choose multiple and complementary umbrella species to assess the state of biodiversity. © 2013 Society for Conservation Biology.

Genetic insights into the mechanisms of Fgf signaling

PubMed Central

Brewer, J. Richard; Mazot, Pierre; Soriano, Philippe

2016-01-01

The fibroblast growth factor (Fgf) family of ligands and receptor tyrosine kinases is required throughout embryonic and postnatal development and also regulates multiple homeostatic functions in the adult. Aberrant Fgf signaling causes many congenital disorders and underlies multiple forms of cancer. Understanding the mechanisms that govern Fgf signaling is therefore important to appreciate many aspects of Fgf biology and disease. Here we review the mechanisms of Fgf signaling by focusing on genetic strategies that enable in vivo analysis. These studies support an important role for Erk1/2 as a mediator of Fgf signaling in many biological processes but have also provided strong evidence for additional signaling pathways in transmitting Fgf signaling in vivo. PMID:27036966

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis.

PubMed

Du, Yushen; Wu, Nicholas C; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting; Sun, Ren

2016-11-01

Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. To fully comprehend the diverse functions of a protein, it is essential to understand the functionality of individual residues. Current methods are highly dependent on evolutionary sequence conservation, which is usually limited by sampling size. Sequence conservation-based methods are further confounded by structural constraints and multifunctionality of proteins. Here we present a method that can systematically identify and annotate functional residues of a given protein. We used a high-throughput functional profiling platform to identify essential residues. Coupling it with homologous-structure comparison, we were able to annotate multiple functions of proteins. We demonstrated the method with the PB1 protein of influenza A virus and identified novel functional residues in addition to its canonical function as an RNA-dependent RNA polymerase. Not limited to virology, this method is generally applicable to other proteins that can be functionally selected and about which homologous-structure information is available. Copyright © 2016 Du et al.

Introduction.

PubMed

Tepikin, Alexei V

2017-01-01

In the title of this part of the book, the tail is wagging not just in a single dog but multiple dogs; in other words, a single process SOCE (tail) somehow involves a cross talk of (wagging) large and powerful organelle and cellular compartments (dogs). So how is this possible? Is this really necessary? Is the title actually appropriate?SOCE is a rather special process, it allows efficient signaling based on a ubiquitous second messenger (Ca 2+ ) in multiple cell and tissue types, it has specific signaling modality (i.e., some downstream reactions depend specifically on SOCE and not just on global Ca 2+ increase), it is vital for the normal functioning of multiple types of cells and tissues, and when misregulated it induces important pathological processes. The reader hopefully agree that such an important "tail" is more appropriate for a kangaroo than for a Chihuahua and that it has awesome wagging capacity.

Quantifying patterns of change in marine ecosystem response to multiple pressures.

PubMed

Large, Scott I; Fay, Gavin; Friedland, Kevin D; Link, Jason S

2015-01-01

The ability to understand and ultimately predict ecosystem response to multiple pressures is paramount to successfully implement ecosystem-based management. Thresholds shifts and nonlinear patterns in ecosystem responses can be used to determine reference points that identify levels of a pressure that may drastically alter ecosystem status, which can inform management action. However, quantifying ecosystem reference points has proven elusive due in large part to the multi-dimensional nature of both ecosystem pressures and ecosystem responses. We used ecological indicators, synthetic measures of ecosystem status and functioning, to enumerate important ecosystem attributes and to reduce the complexity of the Northeast Shelf Large Marine Ecosystem (NES LME). Random forests were used to quantify the importance of four environmental and four anthropogenic pressure variables to the value of ecological indicators, and to quantify shifts in aggregate ecological indicator response along pressure gradients. Anthropogenic pressure variables were critical defining features and were able to predict an average of 8-13% (up to 25-66% for individual ecological indicators) of the variation in ecological indicator values, whereas environmental pressures were able to predict an average of 1-5 % (up to 9-26% for individual ecological indicators) of ecological indicator variation. Each pressure variable predicted a different suite of ecological indicator's variation and the shapes of ecological indicator responses along pressure gradients were generally nonlinear. Threshold shifts in ecosystem response to exploitation, the most important pressure variable, occurred when commercial landings were 20 and 60% of total surveyed biomass. Although present, threshold shifts in ecosystem response to environmental pressures were much less important, which suggests that anthropogenic pressures have significantly altered the ecosystem structure and functioning of the NES LME. Gradient response curves provide ecologically informed transformations of pressure variables to explain patterns of ecosystem structure and functioning. By concurrently identifying thresholds for a suite of ecological indicator responses to multiple pressures, we demonstrate that ecosystem reference points can be evaluated and used to support ecosystem-based management.

Stress Physiology in Infancy and Early Childhood: Cortisol Flexibility, Attunement and Coordination.

PubMed

Atkinson, L; Jamieson, B; Khoury, J; Ludmer, J; Gonzalez, A

2016-08-01

Research on stress physiology in infancy has assumed increasing importance due to its lifelong implications. In this review, we focus on measurement of hypothalamic-pituitary-adrenal (HPA) function, in particular, and on complementary autonomic processes. We suggest that the measure of HPA function has been overly exclusive, focusing on individual reactivity to single, pragmatically selected laboratory challenges. We advocate use of multiple, strategically chosen challenges and within-subject designs. By administering one challenge that typically does not provoke reactivity and another that does, it is possible to represent allostatic load in terms of "flexibility," the capacity to titrate response to challenge. We also recommend assessing infant reactivity in the context of the primary caregiver's physiological function. Infant-mother "attunement" is central to developmental psychology, permeating diverse developmental domains with varied consequences. A review of adrenocortical attunement suggests that attunement is a reliable process, manifest across varied populations. However, attunement appears stronger in the context of more highly stressful circumstances, such that administration of multiple, selected challenges may help evaluate the degree to which individuals titrate attunement to challenge and determine the correlates of this differential attunement. Finally, we advocate studying the "coordination" of HPA function with other aspects of stress physiology and variation in the degree of this coordination. The use of multiple stressors is important here because each stress system is differentially sensitive to different types of challenge. Therefore, use of single stressors in between-subject designs impedes full recognition of the role played by each system. Overall, we recommend measure of flexibility, attunement, and coordination in the context of multiple challenges to capture allostasis in environmental and physiological context. The simultaneous use of such inclusive and integrative metrics may yield more reliable findings than has hitherto been the case. The interrelation of these metrics can be understood in the context of the adaptive calibration model.. © 2016 British Society for Neuroendocrinology.

Proteomic analysis of lung tissue by DIGE

USDA-ARS?s Scientific Manuscript database

Lungs perform an essential physiological function, mediated by a complex series of events that involve the coordination of multiple cell types to support not only gaseous exchange, but homeostasis and protection from infection. Guinea pigs are an important animal disease model for a number of infect...

The brain map of gait variability in aging, cognitive impairment and dementia. A systematic review

PubMed Central

Tian, Qu; Chastan, Nathalie; Bair, Woei-Nan; Resnick, Susan M.; Ferrucci, Luigi; Studenski, Stephanie A.

2017-01-01

While gait variability may reflect subtle changes due to aging or cognitive impairment (CI), associated brain characteristics remain unclear. We summarize structural and functional neuroimaging findings associated with gait variability in older adults with and without CI and dementia. We identified 17 eligible studies; all were cross-sectional; few examined multiple brain areas. In older adults, temporal gait variability was associated with structural differences in medial areas important for lower limb coordination and balance. Both temporal and spatial gait variability were associated with structural and functional differences in hippocampus and primary sensorimotor cortex and structural differences in anterior cingulate cortex, basal ganglia, association tracts, and posterior thalamic radiation. In CI or dementia, some associations were found in primary motor cortex, hippocampus, prefrontal cortex and basal ganglia. In older adults, gait variability may be associated with areas important for sensorimotor integration and coordination. To comprehend the neural basis of gait variability with aging and CI, longitudinal studies of multiple brain areas are needed. PMID:28115194

Modeling the effects of AADT on predicting multiple-vehicle crashes at urban and suburban signalized intersections.

PubMed

Chen, Chen; Xie, Yuanchang

2016-06-01

Annual Average Daily Traffic (AADT) is often considered as a main covariate for predicting crash frequencies at urban and suburban intersections. A linear functional form is typically assumed for the Safety Performance Function (SPF) to describe the relationship between the natural logarithm of expected crash frequency and covariates derived from AADTs. Such a linearity assumption has been questioned by many researchers. This study applies Generalized Additive Models (GAMs) and Piecewise Linear Negative Binomial (PLNB) regression models to fit intersection crash data. Various covariates derived from minor-and major-approach AADTs are considered. Three different dependent variables are modeled, which are total multiple-vehicle crashes, rear-end crashes, and angle crashes. The modeling results suggest that a nonlinear functional form may be more appropriate. Also, the results show that it is important to take into consideration the joint safety effects of multiple covariates. Additionally, it is found that the ratio of minor to major-approach AADT has a varying impact on intersection safety and deserves further investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

Modeling non-linear growth responses to temperature and hydrology in wetland trees

NASA Astrophysics Data System (ADS)

Keim, R.; Allen, S. T.

2016-12-01

Growth responses of wetland trees to flooding and climate variations are difficult to model because they depend on multiple, apparently interacting factors, but are a critical link in hydrological control of wetland carbon budgets. To more generally understand tree growth to hydrological forcing, we modeled non-linear responses of tree ring growth to flooding and climate at sub-annual time steps, using Vaganov-Shashkin response functions. We calibrated the model to six baldcypress tree-ring chronologies from two hydrologically distinct sites in southern Louisiana, and tested several hypotheses of plasticity in wetlands tree responses to interacting environmental variables. The model outperformed traditional multiple linear regression. More importantly, optimized response parameters were generally similar among sites with varying hydrological conditions, suggesting generality to the functions. Model forms that included interacting responses to multiple forcing factors were more effective than were single response functions, indicating the principle of a single limiting factor is not correct in wetlands and both climatic and hydrological variables must be considered in predicting responses to hydrological or climate change.

Leaf venation: structure, function, development, evolution, ecology and applications in the past, present and future.

PubMed

Sack, Lawren; Scoffoni, Christine

2013-06-01

The design and function of leaf venation are important to plant performance, with key implications for the distribution and productivity of ecosystems, and applications in paleobiology, agriculture and technology. We synthesize classical concepts and the recent literature on a wide range of aspects of leaf venation. We describe 10 major structural features that contribute to multiple key functions, and scale up to leaf and plant performance. We describe the development and plasticity of leaf venation and its adaptation across environments globally, and a new global data compilation indicating trends relating vein length per unit area to climate, growth form and habitat worldwide. We synthesize the evolution of vein traits in the major plant lineages throughout paleohistory, highlighting the multiple origins of individual traits. We summarize the strikingly diverse current applications of leaf vein research in multiple fields of science and industry. A unified core understanding will enable an increasing range of plant biologists to incorporate leaf venation into their research. © 2013 The Authors New Phytologist © 2013 New Phytologist Trust.

Photometry of icy satellites: How important is multiple scattering in diluting shadows?

NASA Technical Reports Server (NTRS)

Buratti, B.; Veverka, J.

1984-01-01

Voyager observations have shown that the photometric properties of icy satellites are influenced significantly by large-scale roughness elements on the surfaces. While recent progress was made in treating the photometric effects of macroscopic roughness, it is still the case that even the most complete models do not account for the effects of multiple scattering fully. Multiple scattering dilutes shadows caused by large-scale features, yet for any specific model it is difficult to calculate the amount of dilution as a function of albedo. Accordingly, laboratory measurements were undertaken using the Cornell Goniometer to evaluate the magnitude of the effect.

Articles on Psychology in Communist China

DTIC Science & Technology

1960-06-21

of psychopathy are the confusion of the functions of the brain with those of mental obstacles. The work for the prevention and cure of psychopathy ...analysis of pathology, the etiology of psychopathy is complex and multiple. Of course, ,tne psychogenic factors are of importance in the development of... psychopathy , and some even assume the chief importance. In addition to physical examination as a basis, the diagnosis of psychopathy has to infer

CRISPR Display: A modular method for locus-specific targeting of long noncoding RNAs and synthetic RNA devices in vivo

PubMed Central

Shechner, David M.; Hacisüleyman, Ezgi; Younger, Scott T.; Rinn, John L.

2016-01-01

Noncoding RNAs (ncRNAs) comprise an important class of regulatory molecules that mediate a vast array of biological processes. This broad functional capacity has also facilitated the design of artificial ncRNAs with novel functions. To further investigate and harness these capabilities, we developed CRISPR-Display (“CRISP-Disp”), a targeted localization method that uses Sp. Cas9 to deploy large RNA cargos to DNA loci. We demonstrate that exogenous RNA domains can be functionally appended onto the CRISPR scaffold at multiple insertion points, allowing the construction of Cas9 complexes with protein-binding cassettes, artificial aptamers, pools of random sequences, and RNAs up to 4.8 kilobases in length, including natural lncRNAs. Unlike most existing CRISPR methods, CRISP-Disp allows simultaneous multiplexing of distinct functions at multiple targets, limited only by the number of available functional RNA motifs. We anticipate that this technology will provide a powerful method with which to ectopically localize functional RNAs and ribonucleoprotein (RNP) complexes at specified genomic loci. PMID:26030444

Perceived discrimination, family functioning, and depressive symptoms among immigrant women in Taiwan.

PubMed

Yang, Hao-Jan; Wu, Jyun-Yi; Huang, Sheng-Shiung; Lien, Mei-Huei; Lee, Tony Szu-Hsien

2014-10-01

This study examined the moderating effect of family functioning on the relationship between perceived discrimination and depressive symptoms in immigrant women. A total of 239 immigrant women were selected from four administrative regions in Central Taiwan. Questionnaires concerning perceived discrimination, family functioning (including family cohesion and family adaptability), depressive symptoms, and demographic characteristics were completed by either women themselves (N = 120) or their husbands (N = 119). The moderating effect of family functioning on the relationship between perceived discrimination and depression symptoms was analyzed using multiple regression analysis. Findings showed that a higher level of perceived discrimination among immigrant women is associated with more severe depressive symptoms. Family functioning serves as a moderator between the relationship of perceived discrimination and depressive symptoms, but the moderating effect of family adaptability was evident only in data reported by immigrant women. The results indicate that perceived discrimination has negative mental health implications, and also point to the importance of family functioning for depression. Findings suggest that providers should consider addressing immigrant women's mental health needs through declining their psychosocial distress at multiple ecological levels.

Diversity Performance Analysis on Multiple HAP Networks.

PubMed

Dong, Feihong; Li, Min; Gong, Xiangwu; Li, Hongjun; Gao, Fengyue

2015-06-30

One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques.

Characterizing individual differences in functional connectivity using dual-regression and seed-based approaches.

PubMed

Smith, David V; Utevsky, Amanda V; Bland, Amy R; Clement, Nathan; Clithero, John A; Harsch, Anne E W; McKell Carter, R; Huettel, Scott A

2014-07-15

A central challenge for neuroscience lies in relating inter-individual variability to the functional properties of specific brain regions. Yet, considerable variability exists in the connectivity patterns between different brain areas, potentially producing reliable group differences. Using sex differences as a motivating example, we examined two separate resting-state datasets comprising a total of 188 human participants. Both datasets were decomposed into resting-state networks (RSNs) using a probabilistic spatial independent component analysis (ICA). We estimated voxel-wise functional connectivity with these networks using a dual-regression analysis, which characterizes the participant-level spatiotemporal dynamics of each network while controlling for (via multiple regression) the influence of other networks and sources of variability. We found that males and females exhibit distinct patterns of connectivity with multiple RSNs, including both visual and auditory networks and the right frontal-parietal network. These results replicated across both datasets and were not explained by differences in head motion, data quality, brain volume, cortisol levels, or testosterone levels. Importantly, we also demonstrate that dual-regression functional connectivity is better at detecting inter-individual variability than traditional seed-based functional connectivity approaches. Our findings characterize robust-yet frequently ignored-neural differences between males and females, pointing to the necessity of controlling for sex in neuroscience studies of individual differences. Moreover, our results highlight the importance of employing network-based models to study variability in functional connectivity. Copyright © 2014 Elsevier Inc. All rights reserved.

Physical exam of the adolescent shoulder: tips for evaluating and diagnosing common shoulder disorders in the adolescent athlete.

PubMed

Lazaro, Lionel E; Cordasco, Frank A

2017-02-01

In the young athlete, the shoulder is one of the most frequently injured joints during sports activities. The injuries are either from an acute traumatic event or overuse. Shoulder examination can present some challenges; given the multiple joints involved, the difficulty palpating the underlying structures, and the potential to have both intra- and/or extra-articular problems. Many of the shoulder examination tests can be positive in multiple problems. They usually have high sensitivity but low specificity and therefore low predictive value. The medical history coupled with a detailed physical exam can usually provide the information necessary to obtain an accurate diagnosis. A proficient shoulder examination and the development of an adequate differential diagnosis are important before considering advanced imaging. The shoulder complex relies upon the integrity of multiple structures for normal function. A detailed history is of paramount importance when evaluating young athletes with shoulder problems. A systematic physical examination is extremely important to guiding an accurate diagnosis. The patient's age and activity level are very important when considering the differential diagnosis. Findings obtain through history and physical examination should dictate the decision to obtain advanced imaging of the shoulder.

Core Promoter Functions in the Regulation of Gene Expression of Drosophila Dorsal Target Genes*

PubMed Central

Zehavi, Yonathan; Kuznetsov, Olga; Ovadia-Shochat, Avital; Juven-Gershon, Tamar

2014-01-01

Developmental processes are highly dependent on transcriptional regulation by RNA polymerase II. The RNA polymerase II core promoter is the ultimate target of a multitude of transcription factors that control transcription initiation. Core promoters consist of core promoter motifs, e.g. the initiator, TATA box, and the downstream core promoter element (DPE), which confer specific properties to the core promoter. Here, we explored the importance of core promoter functions in the dorsal-ventral developmental gene regulatory network. This network includes multiple genes that are activated by different nuclear concentrations of Dorsal, an NFκB homolog transcription factor, along the dorsal-ventral axis. We show that over two-thirds of Dorsal target genes contain DPE sequence motifs, which is significantly higher than the proportion of DPE-containing promoters in Drosophila genes. We demonstrate that multiple Dorsal target genes are evolutionarily conserved and functionally dependent on the DPE. Furthermore, we have analyzed the activation of key Dorsal target genes by Dorsal, as well as by another Rel family transcription factor, Relish, and the dependence of their activation on the DPE motif. Using hybrid enhancer-promoter constructs in Drosophila cells and embryo extracts, we have demonstrated that the core promoter composition is an important determinant of transcriptional activity of Dorsal target genes. Taken together, our results provide evidence for the importance of core promoter composition in the regulation of Dorsal target genes. PMID:24634215

Parallel Execution of Functional Mock-up Units in Buildings Modeling

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

Ozmen, Ozgur; Nutaro, James J.; New, Joshua Ryan

2016-06-30

A Functional Mock-up Interface (FMI) defines a standardized interface to be used in computer simulations to develop complex cyber-physical systems. FMI implementation by a software modeling tool enables the creation of a simulation model that can be interconnected, or the creation of a software library called a Functional Mock-up Unit (FMU). This report describes an FMU wrapper implementation that imports FMUs into a C++ environment and uses an Euler solver that executes FMUs in parallel using Open Multi-Processing (OpenMP). The purpose of this report is to elucidate the runtime performance of the solver when a multi-component system is imported asmore » a single FMU (for the whole system) or as multiple FMUs (for different groups of components as sub-systems). This performance comparison is conducted using two test cases: (1) a simple, multi-tank problem; and (2) a more realistic use case based on the Modelica Buildings Library. In both test cases, the performance gains are promising when each FMU consists of a large number of states and state events that are wrapped in a single FMU. Load balancing is demonstrated to be a critical factor in speeding up parallel execution of multiple FMUs.« less

Marine biodiversity–ecosystem functions under uncertain environmental futures

PubMed Central

Bulling, Mark T.; Hicks, Natalie; Murray, Leigh; Paterson, David M.; Raffaelli, Dave; White, Piran C. L.; Solan, Martin

2010-01-01

Anthropogenic activity is currently leading to dramatic transformations of ecosystems and losses of biodiversity. The recognition that these ecosystems provide services that are essential for human well-being has led to a major interest in the forms of the biodiversity–ecosystem functioning relationship. However, there is a lack of studies examining the impact of climate change on these relationships and it remains unclear how multiple climatic drivers may affect levels of ecosystem functioning. Here, we examine the roles of two important climate change variables, temperature and concentration of atmospheric carbon dioxide, on the relationship between invertebrate species richness and nutrient release in a model benthic estuarine system. We found a positive relationship between invertebrate species richness and the levels of release of NH4-N into the water column, but no effect of species richness on the release of PO4-P. Higher temperatures and greater concentrations of atmospheric carbon dioxide had a negative impact on nutrient release. Importantly, we found significant interactions between the climate variables, indicating that reliably predicting the effects of future climate change will not be straightforward as multiple drivers are unlikely to have purely additive effects, resulting in increased levels of uncertainty. PMID:20513718

Marine biodiversity-ecosystem functions under uncertain environmental futures.

PubMed

Bulling, Mark T; Hicks, Natalie; Murray, Leigh; Paterson, David M; Raffaelli, Dave; White, Piran C L; Solan, Martin

2010-07-12

Anthropogenic activity is currently leading to dramatic transformations of ecosystems and losses of biodiversity. The recognition that these ecosystems provide services that are essential for human well-being has led to a major interest in the forms of the biodiversity-ecosystem functioning relationship. However, there is a lack of studies examining the impact of climate change on these relationships and it remains unclear how multiple climatic drivers may affect levels of ecosystem functioning. Here, we examine the roles of two important climate change variables, temperature and concentration of atmospheric carbon dioxide, on the relationship between invertebrate species richness and nutrient release in a model benthic estuarine system. We found a positive relationship between invertebrate species richness and the levels of release of NH(4)-N into the water column, but no effect of species richness on the release of PO(4)-P. Higher temperatures and greater concentrations of atmospheric carbon dioxide had a negative impact on nutrient release. Importantly, we found significant interactions between the climate variables, indicating that reliably predicting the effects of future climate change will not be straightforward as multiple drivers are unlikely to have purely additive effects, resulting in increased levels of uncertainty.

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

Saturated hydraulic conductivity of US soils grouped according to textural class and bulk density

USDA-ARS?s Scientific Manuscript database

Importance of the saturated hydraulic conductivity as soil hydraulic property led to the development of multiple pedotransfer functions for estimating it. One approach to estimating Ksat was using textural classes rather than specific textural fraction contents as pedotransfer inputs. The objective...

Saturated hydraulic conductivity of US soils grouped according textural class and bulk density

USDA-ARS?s Scientific Manuscript database

Importance of the saturated hydraulic conductivity as soil hydraulic property led to the development of multiple pedotransfer functions for estimating it. One approach to estimating Ksat was using textural classes rather than specific textural fraction contents as pedotransfer inputs. The objective...

Automated riverine landscape characterization: GIS-based tools for watershed-scale research, assessment, and management

EPA Science Inventory

River systems consist of hydrogeomorphic patches (HPs) that emerge at multiple spatiotemporal scales. Functional process zones (FPZs) are HPs that exist at the river valley scae and are important strata for fraing whole-watershed research questions and management plans. Hierarchi...

LAND-COVER CHARACTERIZATION AND CHANGE DETECTION USING MULTI-TEMPORAL MODIS NDIV DATA

EPA Science Inventory

Land-cover (LC) composition and conversions are important factors that affect ecosystem condition and function. These data are frequently used as a primary data source to generate landscape-based metrics to assess landscape condition at multiple assessment scales. The use of sate...

Loop-loop interactions govern multiple steps in indole-3-glycerol phosphate synthase catalysis

PubMed Central

Zaccardi, Margot J; O'Rourke, Kathleen F; Yezdimer, Eric M; Loggia, Laura J; Woldt, Svenja; Boehr, David D

2014-01-01

Substrate binding, product release, and likely chemical catalysis in the tryptophan biosynthetic enzyme indole-3-glycerol phosphate synthase (IGPS) are dependent on the structural dynamics of the β1α1 active-site loop. Statistical coupling analysis and molecular dynamic simulations had previously indicated that covarying residues in the β1α1 and β2α2 loops, corresponding to Arg54 and Asn90, respectively, in the Sulfolobus sulfataricus enzyme (ssIGPS), are likely important for coordinating functional motions of these loops. To test this hypothesis, we characterized site mutants at these positions for changes in catalytic function, protein stability and structural dynamics for the thermophilic ssIGPS enzyme. Although there were only modest changes in the overall steady-state kinetic parameters, solvent viscosity and solvent deuterium kinetic isotope effects indicated that these amino acid substitutions change the identity of the rate-determining step across multiple temperatures. Surprisingly, the N90A substitution had a dramatic effect on the general acid/base catalysis of the dehydration step, as indicated by the loss of the descending limb in the pH rate profile, which we had previously assigned to Lys53 on the β1α1 loop. These changes in enzyme function are accompanied with a quenching of ps-ns and µs-ms timescale motions in the β1α1 loop as measured by nuclear magnetic resonance studies. Altogether, our studies provide structural, dynamic and functional rationales for the coevolution of residues on the β1α1 and β2α2 loops, and highlight the multiple roles that the β1α1 loop plays in IGPS catalysis. Thus, substitution of covarying residues in the active-site β1α1 and β2α2 loops of indole-3-glycerol phosphate synthase results in functional, structural, and dynamic changes, highlighting the multiple roles that the β1α1 loop plays in enzyme catalysis and the importance of regulating the structural dynamics of this loop through noncovalent interactions with nearby structural elements. PMID:24403092

A Meta-analysis of Multiple Myeloma Risk Regions in African and European Ancestry Populations Identifies Putatively Functional Loci.

PubMed

Rand, Kristin A; Song, Chi; Dean, Eric; Serie, Daniel J; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S; Bock, Cathryn H; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K; Conti, David V; Zimmerman, Todd; Hwang, Amie E; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L; Berndt, Sonja I; Blot, William J; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W Ryan; Stevens, Victoria L; Lieber, Michael R; Goodman, Phyllis J; Hennis, Anselm J M; Hsing, Ann W; Mehta, Jayesh; Kittles, Rick A; Kolb, Suzanne; Klein, Eric A; Leske, Cristina; Murphy, Adam B; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S; Vij, Ravi; Rybicki, Benjamin A; Stanford, Janet L; Signorello, Lisa B; Witte, John S; Ambrosone, Christine B; Bhatti, Parveen; John, Esther M; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F; Hu, Jennifer J; Ziegler, Regina G; Nyante, Sarah J; Bandera, Elisa V; Birmann, Brenda M; Ingles, Sue A; Press, Michael F; Atanackovic, Djordje; Glenn, Martha J; Cannon-Albright, Lisa A; Jones, Brandt; Tricot, Guido; Martin, Thomas G; Kumar, Shaji K; Wolf, Jeffrey L; Deming Halverson, Sandra L; Rothman, Nathaniel; Brooks-Wilson, Angela R; Rajkumar, S Vincent; Kolonel, Laurence N; Chanock, Stephen J; Slager, Susan L; Severson, Richard K; Janakiraman, Nalini; Terebelo, Howard R; Brown, Elizabeth E; De Roos, Anneclaire J; Mohrbacher, Ann F; Colditz, Graham A; Giles, Graham G; Spinelli, John J; Chiu, Brian C; Munshi, Nikhil C; Anderson, Kenneth C; Levy, Joan; Zonder, Jeffrey A; Orlowski, Robert Z; Lonial, Sagar; Camp, Nicola J; Vachon, Celine M; Ziv, Elad; Stram, Daniel O; Hazelett, Dennis J; Haiman, Christopher A; Cozen, Wendy

2016-12-01

Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma. We performed association testing of common variation in eight regions in 1,318 patients with multiple myeloma and 1,480 controls of European ancestry and 1,305 patients with multiple myeloma and 7,078 controls of African ancestry and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (P < 0.05) associated with multiple myeloma risk in persons of African ancestry and persons of European ancestry, and the variant in 3p22.1 was associated in European ancestry only. In a combined African ancestry-European ancestry meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically significantly associated with multiple myeloma risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4 Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR, 1.32; P = 2.93 × 10 -7 ) in TNFRSF13B encodes a lymphocyte-specific protein in the TNF receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7 CONCLUSIONS: We found that reported multiple myeloma susceptibility regions contain risk variants important across populations, supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. A subset of reported risk loci for multiple myeloma has consistent effects across populations and is likely to be functional. Cancer Epidemiol Biomarkers Prev; 25(12); 1609-18. ©2016 AACR. ©2016 American Association for Cancer Research.

Thrombospondins: old players, new games.

PubMed

Stenina-Adognravi, Olga

2013-10-01

Thrombospondins (TSPs) are secreted extracellular matrix (ECM) proteins from TSP family, which consists of five homologous members. They share a complex domain structure and have numerous binding partners in ECM and multiple cell surface receptors. Information that has emerged over the past decade identifies TSPs as important mediators of cellular homeostasis, assigning new important roles in cardiovascular pathology to these proteins. Recent studies of the functions of TSP in the cardiovascular system, diabetes and aging, which placed several TSPs in a position of critical regulators, demonstrated the involvement of these proteins in practically every aspect of cardiovascular pathophysiology related to atherosclerosis: inflammation, immunity, leukocyte recruitment and function, function of vascular cells, angiogenesis, and responses to hypoxia, ischemia and hyperglycemia. TSPs are also critically important in the development and ultimate outcome of the complications associated with atherosclerosis--myocardial infarction, and heart hypertrophy and failure. Their expression and significance increase with age and with the progression of diabetes, two major contributors to the development of atherosclerosis and its complications. This overview of recent literature examines the latest information on the newfound functions of TSPs that emphasize the importance of ECM in cardiovascular homeostasis and pathology. The functions of TSPs in myocardium, vasculature, vascular complications of diabetes, aging and immunity are discussed.

Phenomenology from SIDIS and e+e- multiplicities: multiplicities and phenomenology - part I

NASA Astrophysics Data System (ADS)

Bacchetta, Alessandro; Echevarria, Miguel G.; Radici, Marco; Signori, Andrea

2015-01-01

This study is part of a project to investigate the transverse momentum dependence in parton distribution and fragmentation functions, analyzing (semi-)inclusive high-energy processes within a proper QCD framework. We calculate the transverse-momentum-dependent (TMD) multiplicities for e+e- annihilation into two hadrons (considering different combinations of pions and kaons) aiming to investigate the impact of intrinsic and radiative partonic transverse momentum and their mixing with flavor. Different descriptions of the non-perturbative evolution kernel (see, e.g., Refs. [1-5]) are available on the market and there are 200 sets of flavor configurations for the unpolarized TMD fragmentation functions (FFs) resulting from a Monte Carlo fit of Semi-Inclusive Deep-Inelastic Scattering (SIDIS) data at Hermes (see Ref. [6]). We build our predictions of e+e- multiplicities relying on this rich phenomenology. The comparison of these calculations with future experimental data (from Belle and BaBar collaborations) will shed light on non-perturbative aspects of hadron structure, opening important insights into the physics of spin, flavor and momentum structure of hadrons.

Oxytocin Receptor (OXTR) Methylation and Cognition in Psychotic Disorders.

PubMed

Grove, Tyler B; Burghardt, Kyle J; Kraal, A Zarina; Dougherty, Ryan J; Taylor, Stephan F; Ellingrod, Vicki L

2016-10-01

Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor (OXTR) . Within psychotic disorders, it is unknown if OXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral blood OXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101). Using hierarchical multiple regression analysis, methylation at the Chr3:8767638 site was significantly associated with composite cognitive performance independent of demographic and medication factors while controlling for multiple testing in this combined diagnostic sample (adjusted p = 0.023).

Oxytocin Receptor (OXTR) Methylation and Cognition in Psychotic Disorders

PubMed Central

Grove, Tyler B.; Burghardt, Kyle J.; Kraal, A. Zarina; Dougherty, Ryan J.; Taylor, Stephan F.; Ellingrod, Vicki L.

2016-01-01

Previous reports have identified an association between cognitive impairment and genetic variation in psychotic disorders. In particular, this association may be related to abnormal regulation of genes responsible for broad cognitive functions such as the oxytocin receptor (OXTR). Within psychotic disorders, it is unknown if OXTR methylation, which can have important implications for gene regulation, is related to cognitive function. The current study examined peripheral blood OXTR methylation and general cognition in people with schizophrenia, schizoaffective disorder, and psychotic disorder not otherwise specified (N = 101). Using hierarchical multiple regression analysis, methylation at the Chr3:8767638 site was significantly associated with composite cognitive performance independent of demographic and medication factors while controlling for multiple testing in this combined diagnostic sample (adjusted p = 0.023). PMID:27867940

Functional sub-division of the Drosophila genome via chromatin looping

PubMed Central

Ahanger, Sajad H.; Shouche, Yogesh S.; Mishra, Rakesh K.

2013-01-01

Insulators help in organizing the eukaryotic genomes into physically and functionally autonomous regions through the formation of chromatin loops. Recent findings in Drosophila and vertebrates suggest that insulators anchor multiple loci through long-distance interactions which may be mechanistically linked to insulator function. Important to such processes in Drosophila is CP190, a common co-factor of insulator complexes. CP190 is also known to associate with the nuclear matrix, components of the RNAi machinery, active promoters and borders of the repressive chromatin domains. Although CP190 plays a pivotal role in insulator function in Drosophila, vertebrates lack a probable functional equivalent of CP190 and employ CTCF as the major factor to carry out insulator function/chromatin looping. In this review, we discuss the emerging role of CP190 in tethering genome, specifically in the perspective of insulator function in Drosophila. Future studies aiming genome-wide role of CP190 in chromatin looping is likely to give important insights into the mechanism of genome organization. PMID:23333867

Influence of predator density on nonindependent effects of multiple predator species.

PubMed

Griffen, Blaine D; Williamson, Tucker

2008-02-01

Interactions between multiple predator species are frequent in natural communities and can have important implications for shared prey survival. Predator density may be an important component of these interactions between predator species, as the frequency of interactions between species is largely determined by species density. Here we experimentally examine the importance of predator density for interactions between predator species and subsequent impacts on prey. We show that aggressive interactions between the predatory shore crabs Carcinus maenas and Hemigrapsus sanguineus increased with predator density, yet did not increase as fast as negative interactions between conspecifics. At low density, interactions between conspecific and heterospecific predators had similar inhibitory impacts on predator function, whereas conspecific interference was greater than interference from heterospecifics at high predator density. Thus the impact of conspecific interference at high predator density was sufficient in itself that interactions with a second predator species had no additional impact on per capita predation. Spatial and temporal variability in predator density is a ubiquitous characteristic of natural systems that should be considered in studies of multiple predator species.

An integrated miRNA functional screening and target validation method for organ morphogenesis.

PubMed

Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

2016-03-16

The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

TEMPORAL NEUROTRANSMITTER CONDITIONING RESTORES THE FUNCTIONAL ACTIVITY OF ADULT SPINAL-CORD NEURONS IN LONG-TERM CULTURE

PubMed Central

Das, Mainak; Bhargava, Neelima; Bhalkikar, Abhijeet; Kang, Jung Fong; Hickman, James J

2008-01-01

The ability to culture functional adult mammalian spinal-cord neurons represents an important step in the understanding and treatment of a spectrum of neurological disorders including spinal cord injury. Previously, the limited functional recovery of these cells, as characterized by a diminished ability to initiate action potentials and to exhibit repetitive firing patterns, has arisen as a major impediment to their physiological relevance. In this report we demonstrate that single temporal doses of the neurotransmitters serotonin, glutamate (N-acetyl-DL-glutamic acid) and acetylcholine-chloride leads to the full electrophysiological functional recovery of adult mammalian spinal-cord neurons, when they are cultured under defined serum-free conditions. Approximately 60% of the neurons treated regained their electrophysiological signature, often firing single, double and, most importantly, multiple action potentials. PMID:18005959

Domain General Mediators of the Relation between Kindergarten Number Sense and First-Grade Mathematics Achievement

PubMed Central

Hassinger-Das, Brenna; Jordan, Nancy C.; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2013-01-01

Domain general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that attention problems and executive functioning both were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance while executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. PMID:24237789

Domain-general mediators of the relation between kindergarten number sense and first-grade mathematics achievement.

PubMed

Hassinger-Das, Brenna; Jordan, Nancy C; Glutting, Joseph; Irwin, Casey; Dyson, Nancy

2014-02-01

Domain-general skills that mediate the relation between kindergarten number sense and first-grade mathematics skills were investigated. Participants were 107 children who displayed low number sense in the fall of kindergarten. Controlling for background variables, multiple regression analyses showed that both attention problems and executive functioning were unique predictors of mathematics outcomes. Attention problems were more important for predicting first-grade calculation performance, whereas executive functioning was more important for predicting first-grade performance on applied problems. Moreover, both executive functioning and attention problems were unique partial mediators of the relationship between kindergarten and first-grade mathematics skills. The results provide empirical support for developing interventions that target executive functioning and attention problems in addition to instruction in number skills for kindergartners with initial low number sense. Copyright © 2013 Elsevier Inc. All rights reserved.

Episodic Memory in Former Professional Football Players with a History of Concussion: An Event-Related Functional Neuroimaging Study

PubMed Central

Giovanello, Kelly S.; Guskiewicz, Kevin M.

2013-01-01

Abstract Previous research has demonstrated that sport-related concussions can have short-term effects on cognitive processes, but the long-term consequences are less understood and warrant more research. This study was the first to use event-related functional magnetic resonance imaging (fMRI) to examine long-term differences in neural activity during memory tasks in former athletes who have sustained multiple sport-related concussions. In an event-related fMRI study, former football players reporting multiple sport-related concussions (i.e., three or more) were compared with players who reported fewer than three concussions during a memory paradigm examining item memory (i.e., memory for the particular elements of an event) and relational memory (i.e., memory for the relationships between elements). Behaviorally, we observed that concussion history did not significantly affect behavioral performance, because persons in the low and high concussion groups had equivalent performance on both memory tasks, and in addition, that concussion history was not associated with any behavioral memory measures. Despite demonstrating equivalent behavioral performance, the two groups of former players demonstrated different neural recruitment patterns during relational memory retrieval, suggesting that multiple concussions may be associated with functional inefficiencies in the relational memory network. In addition, the number of previous concussions significantly correlated with functional activity in a number of brain regions, including the medial temporal lobe and inferior parietal lobe. Our results provide important insights in understanding the long-term functional consequences of sustaining multiple sports-related concussions. PMID:23679098

In vivo optical modulation of neural signals using monolithically integrated two-dimensional neural probe arrays

PubMed Central

Son, Yoojin; Jenny Lee, Hyunjoo; Kim, Jeongyeon; Shin, Hyogeun; Choi, Nakwon; Justin Lee, C.; Yoon, Eui-Sung; Yoon, Euisik; Wise, Kensall D.; Geun Kim, Tae; Cho, Il-Joo

2015-01-01

Integration of stimulation modalities (e.g. electrical, optical, and chemical) on a large array of neural probes can enable an investigation of important underlying mechanisms of brain disorders that is not possible through neural recordings alone. Furthermore, it is important to achieve this integration of multiple functionalities in a compact structure to utilize a large number of the mouse models. Here we present a successful optical modulation of in vivo neural signals of a transgenic mouse through our compact 2D MEMS neural array (optrodes). Using a novel fabrication method that embeds a lower cladding layer in a silicon substrate, we achieved a thin silicon 2D optrode array that is capable of delivering light to multiple sites using SU-8 as a waveguide core. Without additional modification to the microelectrodes, the measured impedance of the multiple microelectrodes was below 1 MΩ at 1 kHz. In addition, with a low background noise level (±25 μV), neural spikes from different individual neurons were recorded on each microelectrode. Lastly, we successfully used our optrodes to modulate the neural activity of a transgenic mouse through optical stimulation. These results demonstrate the functionality of the 2D optrode array and its potential as a next-generation tool for optogenetic applications. PMID:26494437

Multipronged CD4 T cell effector and memory responses cooperate to provide potent immunity against respiratory virus

PubMed Central

Strutt, Tara M.; McKinstry, K. Kai; Marshall, Nikki B.; Vong, Allen M.; Dutton, Richard W.; Swain, Susan L.

2014-01-01

Summary Over the last decade, the known spectrum of CD4 T cell effect or subsets has become much broader and it has become clear that there are multiple dimensions by which subsets with a particular cytokine commitment can be further defined, including their stage of differentiation, their location and most importantly, their ability to carryout discrete functions. Here we focus on our studies that highlight the synergy among discrete subsets, especially those defined by helper and cytotoxic function, in mediating viral protection and on distinctions between CD4 T cell effectors located in spleen, draining lymph node, and in tissue sites of infection. What emerges is a surprising multiplicity of CD4 T cell functions that indicate a large arsenal of mechanisms by which CD4 T cells act to combat viruses. PMID:23947353

Effect of multiple circular holes Fraunhofer diffraction for the infrared optical imaging

NASA Astrophysics Data System (ADS)

Lu, Chunlian; Lv, He; Cao, Yang; Cai, Zhisong; Tan, Xiaojun

2014-11-01

With the development of infrared optics, infrared optical imaging systems play an increasingly important role in modern optical imaging systems. Infrared optical imaging is used in industry, agriculture, medical, military and transportation. But in terms of infrared optical imaging systems which are exposed for a long time, some contaminations will affect the infrared optical imaging. When the contamination contaminate on the lens surface of the optical system, it would affect diffraction. The lens can be seen as complementary multiple circular holes screen happen Fraunhofer diffraction. According to Babinet principle, you can get the diffraction of the imaging system. Therefore, by studying the multiple circular holes Fraunhofer diffraction, conclusions can be drawn about the effect of infrared imaging. This paper mainly studies the effect of multiple circular holes Fraunhofer diffraction for the optical imaging. Firstly, we introduce the theory of Fraunhofer diffraction and Point Spread Function. Point Spread Function is a basic tool to evaluate the image quality of the optical system. Fraunhofer diffraction will affect Point Spread Function. Then, the results of multiple circular holes Fraunhofer diffraction are given for different hole size and hole spacing. We choose the hole size from 0.1mm to 1mm and hole spacing from 0.3mm to 0.8mm. The infrared wavebands of optical imaging are chosen from 1μm to 5μm. We use the MATLAB to simulate light intensity distribution of multiple circular holes Fraunhofer diffraction. Finally, three-dimensional diffraction maps of light intensity are given to contrast.

How biological soil crusts became recognized as a functional unit: a selective history

USGS Publications Warehouse

Lange, Otto L.; Belnap, Jayne

2016-01-01

It is surprising that despite the world-wide distribution and general importance of biological soil crusts (biocrusts), scientific recognition and functional analysis of these communities is a relatively young field of science. In this chapter, we sketch the historical lines that led to the recognition of biocrusts as a community with important ecosystem functions. The idea of biocrusts as a functional ecological community has come from two main scientific branches: botany and soil science. For centuries, botanists have long recognized that multiple organisms colonize the soil surface in the open and often dry areas occurring between vascular plants. Much later, after the initial taxonomic and phyto-sociological descriptions were made, soil scientists and agronomists observed that these surface organisms interacted with soils in ways that changed the soil structure. In the 1970’s, research on these communities as ecological units that played an important functional role in drylands began in earnest, and these studies have continued to this day. Here, we trace the history of these studies from the distant past until 1990, when biocrusts became well-known to scientists and the public.

Imbalanced multi-modal multi-label learning for subcellular localization prediction of human proteins with both single and multiple sites.

PubMed

He, Jianjun; Gu, Hong; Liu, Wenqi

2012-01-01

It is well known that an important step toward understanding the functions of a protein is to determine its subcellular location. Although numerous prediction algorithms have been developed, most of them typically focused on the proteins with only one location. In recent years, researchers have begun to pay attention to the subcellular localization prediction of the proteins with multiple sites. However, almost all the existing approaches have failed to take into account the correlations among the locations caused by the proteins with multiple sites, which may be the important information for improving the prediction accuracy of the proteins with multiple sites. In this paper, a new algorithm which can effectively exploit the correlations among the locations is proposed by using gaussian process model. Besides, the algorithm also can realize optimal linear combination of various feature extraction technologies and could be robust to the imbalanced data set. Experimental results on a human protein data set show that the proposed algorithm is valid and can achieve better performance than the existing approaches.

[Effect of preventive treatment on cognitive performance in patients with multiple sclerosis].

PubMed

Shorobura, Maria S

2018-01-01

Introduction: cognitive, emotional and psychopathological changes play a significant role in the clinical picture of multiple sclerosis and influence the effectiveness of drug therapy, working capacity, quality of life, and the process of rehabilitation of patients with multiple sclerosis. The aim: investigate the changes in cognitive function in patients with multiple sclerosis, such as information processing speed and working memory of patients before and after treatment with immunomodulating drug. Materials and methods:33 patients examined reliably diagnosed with multiple sclerosis who were treated with preventive examinations and treatment from 2012 to 2016. For all patients with multiple sclerosis had clinical-neurological examination (neurological status using the EDSS scale) and the cognitive status was evaluated using the PASAT auditory test. Patient screening was performed before, during and after the therapy. Statistical analysis of the results was performed in the system Statistica 8.0. We used Student's t-test (t), Mann-Whitney test (Z). Person evaluated the correlation coefficients and Spearman (r, R), Wilcoxon criterion (T), Chi-square (X²). Results: The age of patients with multiple sclerosis affects the growth and EDSS scale score decrease PASAT to treatment. Duration of illness affects the EDSS scale score and performance PASAT. Indicators PASAT not significantly decreased throughout the treatment. Conclusions: glatiramer acetate has a positive effect on cognitive function, information processing speed and working memory patients with multiple sclerosis, which is one of the important components of the therapeutic effect of this drug.

Analysis of Globodera rostochiensis effectors reveals conserved functions of SPRYSEC proteins in suppressing and eliciting plant immune responses

USDA-ARS?s Scientific Manuscript database

Potato cyst nematodes (PCNs), including Globodera rostochiensis (Woll.), are important pests of potato. Plant parasitic nematodes produce multiple effector proteins, secreted from their stylets, to successfully infect their hosts. These include proteins that are delivered to the apoplast, as well as...

MUD for Learning: Classification and Instruction

ERIC Educational Resources Information Center

Hsieh, Chung-Hsiang; Sun, Chuen-Tsai

2006-01-01

From a constructivist point of view, the importance of MUDs (Multiple User Dungeons) in education is justified based on their community-forming, learning, and role-playing functions. The authors propose a typology for educational MUDs and discuss their individual instructional approaches in order to measure MUD potential in ten-os of…

Travel time analysis for a subsurface drained sub-watershed in Upper Big Walnut Creek Watershed, Ohio

USDA-ARS?s Scientific Manuscript database

Runoff travel time, which is a function of watershed and storm characteristics, is an important parameter affecting the prediction accuracy of hydrologic models. Although, time of concentration (tc) is a most widely used time parameter, it has multiple conceptual and computational definitions. Most ...

β-Ocimene, a Key Floral and Foliar Volatile Involved in Multiple Interactions between Plants and Other Organisms.

PubMed

Farré-Armengol, Gerard; Filella, Iolanda; Llusià, Joan; Peñuelas, Josep

2017-07-13

β-Ocimene is a very common plant volatile released in important amounts from the leaves and flowers of many plant species. This acyclic monoterpene can play several biological functions in plants, by potentially affecting floral visitors and also by mediating defensive responses to herbivory. The ubiquity and high relative abundance of β-ocimene in the floral scents of species from most plant families and from different pollination syndromes (ranging from generalism to specialism) strongly suggest that this terpenoid may play an important role in the attraction of pollinators to flowers. We compiled abundant evidence from published studies that supports β-ocimene as a generalist attractant of a wide spectrum of pollinators. We found no studies testing behavioural responses of pollinators to β-ocimene, that could directly demonstrate or deny the function of β-ocimene in pollinator attraction; but several case studies support that the emissions of β-ocimene in flowers of different species follow marked temporal and spatial patterns of emission, which are typical from floral volatile organic compound (VOC) emissions that are involved in pollinator attraction. Furthermore, important β-ocimene emissions are induced from vegetative plant tissues after herbivory in many species, which have relevant functions in the establishment of tritrophic interactions. We thus conclude that β-ocimene is a key plant volatile with multiple relevant functions in plants, depending on the organ and the time of emission. Experimental behavioural studies on pure β-ocimene conducted with pollinating insects will be necessary to prove the assumptions made here.

The role of recurrent disturbances for ecosystem multifunctionality.

PubMed

Villnäs, Anna; Norkko, Joanna; Hietanen, Susanna; Josefson, Alf B; Lukkari, Kaarina; Norkko, Alf

2013-10-01

Ecosystem functioning is threatened by an increasing number of anthropogenic stressors, creating a legacy of disturbance that undermines ecosystem resilience. However, few empirical studies have assessed to what extent an ecosystem can tolerate repeated disturbances and sustain its multiple functions. By inducing increasingly recurring hypoxic disturbances to a sedimentary ecosystem, we show that the majority of individual ecosystem functions experience gradual degradation patterns in response to repetitive pulse disturbances. The degradation in overall ecosystem functioning was, however, evident at an earlier stage than for single ecosystem functions and was induced after a short pulse of hypoxia (i.e., three days), which likely reduced ecosystem resistance to further hypoxic perturbations. The increasing number of repeated pulse disturbances gradually moved the system closer to a press response. In addition to the disturbance regime, the changes in benthic trait composition as well as habitat heterogeneity were important for explaining the variability in overall ecosystem functioning. Our results suggest that disturbance-induced responses across multiple ecosystem functions can serve as a warning signal for losses of the adaptive capacity of an ecosystem, and might at an early stage provide information to managers and policy makers when remediation efforts should be initiated.

Adaptive function allocation reduces performance costs of static automation

NASA Technical Reports Server (NTRS)

Parasuraman, Raja; Mouloua, Mustapha; Molloy, Robert; Hilburn, Brian

1993-01-01

Adaptive automation offers the option of flexible function allocation between the pilot and on-board computer systems. One of the important claims for the superiority of adaptive over static automation is that such systems do not suffer from some of the drawbacks associated with conventional function allocation. Several experiments designed to test this claim are reported in this article. The efficacy of adaptive function allocation was examined using a laboratory flight-simulation task involving multiple functions of tracking, fuel-management, and systems monitoring. The results show that monitoring inefficiency represents one of the performance costs of static automation. Adaptive function allocation can reduce the performance cost associated with long-term static automation.

Multitasking in multiple sclerosis: can it inform vocational functioning?

PubMed

Morse, Chelsea L; Schultheis, Maria T; McKeever, Joshua D; Leist, Thomas

2013-12-01

To examine associations between multitasking ability defined by performance on a complex task integrating multiple cognitive domains and vocational functioning in multiple sclerosis (MS). Survey data collection. Laboratory with referrals from an outpatient clinic. Community-dwelling individuals with MS (N=30) referred between October 2011 and June 2012. Not applicable. The modified Six Elements Test (SET) to measure multitasking ability, Fatigue Severity Scale to measure fatigue, several neuropsychological measures of executive functioning, and vocational status. Among the sample, 60% of individuals have reduced their work hours because of MS symptoms (cutback employment group) and 40% had maintained their work hours. Among both groups, SET performance was significantly associated with performance on several measures of neuropsychological functioning. Individuals in the cutback employment group demonstrated significantly worse overall performance on the SET (P=.041). Logistic regression was used to evaluate associations between SET performance and vocational status, while accounting for neuropsychological performance and fatigue. The overall model was significant (χ(2)3=8.65, P=.032), with fatigue [Exp(B)=.83, P=.01] and multitasking ability [Exp(B)=.60, P=.043] retained as significant predictors. Multitasking ability may play an important role in performance at work for individuals with MS. Given that multitasking was associated with vocational functioning, future efforts should assess the usefulness of incorporating multitasking ability into rehabilitation planning. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Interindividual differences in cognitive flexibility: influence of gray matter volume, functional connectivity and trait impulsivity

PubMed Central

Langner, Robert; Cieslik, Edna C.; Rottschy, Claudia; Eickhoff, Simon B.

2016-01-01

Cognitive flexibility, a core aspect of executive functioning, is required for the speeded shifting between different tasks and sets. Using an interindividual differences approach, we examined whether cognitive flexibility, as assessed by the Delis–Kaplan card-sorting test, is associated with gray matter volume (GMV) and functional connectivity (FC) of regions of a core network of multiple cognitive demands as well as with different facets of trait impulsivity. The core multiple-demand network was derived from three large-scale neuroimaging meta-analyses and only included regions that showed consistent associations with sustained attention, working memory as well as inhibitory control. We tested to what extent self-reported impulsivity as well as GMV and resting-state FC in this core network predicted cognitive flexibility independently and incrementally. Our analyses revealed that card-sorting performance correlated positively with GMV of the right anterior insula, FC between bilateral anterior insula and midcingulate cortex/supplementary motor area as well as the impulsivity dimension “Premeditation.” Importantly, GMV, FC and impulsivity together accounted for more variance of card-sorting performance than every parameter alone. Our results therefore indicate that various factors contribute individually to cognitive flexibility, underlining the need to search across multiple modalities when aiming to unveil the mechanisms behind executive functioning. PMID:24878823

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex.

PubMed

Szabó, István; Hormay, Edina; Csetényi, Bettina; Nagy, Bernadett; Lénárd, László; Karádi, Zoltán

2018-02-01

Multiple functional attributes of glucose-monitoring neurons in the medial orbitofrontal (ventrolateral prefrontal) cortex. NEUROSCI BIOBEHAV REV 73(1) XXX-XXX, 2017.- Special chemosensory cells, the glucose-monitoring (GM) neurons, reportedly involved in the central feeding control, exist in the medial orbitofrontal (ventrolateral prefrontal) cortex (mVLPFC). Electrophysiological, metabolic and behavioral studies reveal complex functional attributes of these cells and raise their homeostatic significance. Single neuron recordings, by means of the multibarreled microelectrophoretic technique, elucidate differential sensitivities of limbic forebrain neurons in the rat and the rhesus monkey to glucose and other chemicals, whereas gustatory stimulations demonstrate their distinct taste responsiveness. Metabolic examinations provide evidence for alteration of blood glucose level in glucose tolerance test and elevation of plasma triglyceride concentration after destruction of the local GM cells by streptozotocin (STZ). In behavioral studies, STZ microinjection into the mVLPFC fails to interfere with the acquisition of saccharin conditioned taste avoidance, does cause, however, taste perception deficit in taste reactivity tests. Multiple functional attributes of GM neurons in the mVLPFC, within the frame of the hierarchically organized central GM neuronal network, appear to play important role in the maintenance of the homeostatic balance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of the Complex General Linear Model in the Fourier Domain: Application to fMRI Multiple Input-Output Evoked Responses for Single Subjects

PubMed Central

Rio, Daniel E.; Rawlings, Robert R.; Woltz, Lawrence A.; Gilman, Jodi; Hommer, Daniel W.

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function. PMID:23840281

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

PubMed

Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Color Change for Thermoregulation versus Camouflage in Free-Ranging Lizards.

PubMed

Smith, Kathleen R; Cadena, Viviana; Endler, John A; Kearney, Michael R; Porter, Warren P; Stuart-Fox, Devi

2016-12-01

Animal coloration has multiple functions including thermoregulation, camouflage, and social signaling, and the requirements of each function may sometimes conflict. Many terrestrial ectotherms accommodate the multiple functions of color through color change. However, the relative importance of these functions and how color-changing species accommodate them when they do conflict are poorly understood because we lack data on color change in the wild. Here, we show that the color of individual radio-tracked bearded dragon lizards, Pogona vitticeps, correlates strongly with background color and less strongly, but significantly, with temperature. We found no evidence that individuals simultaneously optimize camouflage and thermoregulation by choosing light backgrounds when hot or dark backgrounds when cold. In laboratory experiments, lizards showed both UV-visible (300-700 nm) and near-infrared (700-2,100 nm) reflectance changes in response to different background and temperature treatments, consistent with camouflage and thermoregulatory functions, respectively, but with no interaction between the two. Overall, our results suggest that wild bearded dragons change color to improve both thermoregulation and camouflage but predominantly adjust for camouflage, suggesting that compromising camouflage may entail a greater potential immediate survival cost.

Network-Level Structure-Function Relationships in Human Neocortex

PubMed Central

Mišić, Bratislav; Betzel, Richard F.; de Reus, Marcel A.; van den Heuvel, Martijn P.; Berman, Marc G.; McIntosh, Anthony R.; Sporns, Olaf

2016-01-01

The dynamics of spontaneous fluctuations in neural activity are shaped by underlying patterns of anatomical connectivity. While numerous studies have demonstrated edge-wise correspondence between structural and functional connections, much less is known about how large-scale coherent functional network patterns emerge from the topology of structural networks. In the present study, we deploy a multivariate statistical technique, partial least squares, to investigate the association between spatially extended structural networks and functional networks. We find multiple statistically robust patterns, reflecting reliable combinations of structural and functional subnetworks that are optimally associated with one another. Importantly, these patterns generally do not show a one-to-one correspondence between structural and functional edges, but are instead distributed and heterogeneous, with many functional relationships arising from nonoverlapping sets of anatomical connections. We also find that structural connections between high-degree hubs are disproportionately represented, suggesting that these connections are particularly important in establishing coherent functional networks. Altogether, these results demonstrate that the network organization of the cerebral cortex supports the emergence of diverse functional network configurations that often diverge from the underlying anatomical substrate. PMID:27102654

Unified Sequence-Based Association Tests Allowing for Multiple Functional Annotations and Meta-analysis of Noncoding Variation in Metabochip Data.

PubMed

He, Zihuai; Xu, Bin; Lee, Seunggeun; Ionita-Laza, Iuliana

2017-09-07

Substantial progress has been made in the functional annotation of genetic variation in the human genome. Integrative analysis that incorporates such functional annotations into sequencing studies can aid the discovery of disease-associated genetic variants, especially those with unknown function and located outside protein-coding regions. Direct incorporation of one functional annotation as weight in existing dispersion and burden tests can suffer substantial loss of power when the functional annotation is not predictive of the risk status of a variant. Here, we have developed unified tests that can utilize multiple functional annotations simultaneously for integrative association analysis with efficient computational techniques. We show that the proposed tests significantly improve power when variant risk status can be predicted by functional annotations. Importantly, when functional annotations are not predictive of risk status, the proposed tests incur only minimal loss of power in relation to existing dispersion and burden tests, and under certain circumstances they can even have improved power by learning a weight that better approximates the underlying disease model in a data-adaptive manner. The tests can be constructed with summary statistics of existing dispersion and burden tests for sequencing data, therefore allowing meta-analysis of multiple studies without sharing individual-level data. We applied the proposed tests to a meta-analysis of noncoding rare variants in Metabochip data on 12,281 individuals from eight studies for lipid traits. By incorporating the Eigen functional score, we detected significant associations between noncoding rare variants in SLC22A3 and low-density lipoprotein and total cholesterol, associations that are missed by standard dispersion and burden tests. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Two SPSS programs for interpreting multiple regression results.

PubMed

Lorenzo-Seva, Urbano; Ferrando, Pere J; Chico, Eliseo

2010-02-01

When multiple regression is used in explanation-oriented designs, it is very important to determine both the usefulness of the predictor variables and their relative importance. Standardized regression coefficients are routinely provided by commercial programs. However, they generally function rather poorly as indicators of relative importance, especially in the presence of substantially correlated predictors. We provide two user-friendly SPSS programs that implement currently recommended techniques and recent developments for assessing the relevance of the predictors. The programs also allow the user to take into account the effects of measurement error. The first program, MIMR-Corr.sps, uses a correlation matrix as input, whereas the second program, MIMR-Raw.sps, uses the raw data and computes bootstrap confidence intervals of different statistics. The SPSS syntax, a short manual, and data files related to this article are available as supplemental materials from http://brm.psychonomic-journals.org/content/supplemental.

Contribution of Insula in Parkinson’s Disease: A Quantitative Meta-Analysis Study

PubMed Central

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E.; Cho, Sang S.; Houle, Sylvain; Strafella, Antonio P.

2016-01-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson’s disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. PMID:26800238

Contribution of insula in Parkinson's disease: A quantitative meta-analysis study.

PubMed

Criaud, Marion; Christopher, Leigh; Boulinguez, Philippe; Ballanger, Benedicte; Lang, Anthony E; Cho, Sang S; Houle, Sylvain; Strafella, Antonio P

2016-04-01

The insula region is known to be an integrating hub interacting with multiple brain networks involved in cognitive, affective, sensory, and autonomic processes. There is growing evidence suggesting that this region may have an important role in Parkinson's disease (PD). Thus, to investigate the functional organization of the insular cortex and its potential role in parkinsonian features, we used a coordinate-based quantitative meta-analysis approach, the activation likelihood estimation. A total of 132 insular foci were selected from 96 published experiments comprising the five functional categories: cognition, affective/behavioral symptoms, bodily awareness/autonomic function, sensorimotor function, and nonspecific resting functional changes associated with the disease. We found a significant convergence of activation maxima related to PD in different insular regions including anterior and posterior regions bilaterally. This study provides evidence of an important functional distribution of different domains within the insular cortex in PD, particularly in relation to nonmotor aspects, with an influence of medication effect. © 2016 Wiley Periodicals, Inc.

How does a planet excite multiple spiral arms?

NASA Astrophysics Data System (ADS)

Bae, Jaehan; Zhu, Zhaohuan

2018-01-01

Protoplanetary disk simulations show that a single planet excites multiple spiral arms in the background disk, potentially supported by the multi-armed spirals revealed with recent high-resolution observations in some disks. The existence of multiple spiral arms is of importance in many aspects. It is empirically found that the arm-to-arm separation increases as a function of the planetary mass, so one can use the morphology of observed spiral arms to infer the mass of unseen planets. In addition, a spiral arm opens a radial gap as it steepens into a shock, so when a planet excites multiple spiral arms it can open multiple gaps in the disk. Despite the important implications, however, the formation mechanism of multiple spiral arms has not been fully understood by far.In this talk, we explain how a planet excites multiple spiral arms. The gravitational potential of a planet can be decomposed into a Fourier series, a sum of individual azimuthal modes having different azimuthal wavenumbers. Using a linear wave theory, we first demonstrate that appropriate sets of Fourier decomposed waves can be in phase, raising a possibility that constructive interference among the waves can produce coherent structures - spiral arms. More than one spiral arm can form since such constructive interference can occur at different positions in the disk for different sets of waves. We then verify this hypothesis using a suite of two-dimensional hydrodynamic simulations. Finally, we present non-linear behavior in the formation of multiple spiral arms.

Functional Multiple-Set Canonical Correlation Analysis

ERIC Educational Resources Information Center

Hwang, Heungsun; Jung, Kwanghee; Takane, Yoshio; Woodward, Todd S.

2012-01-01

We propose functional multiple-set canonical correlation analysis for exploring associations among multiple sets of functions. The proposed method includes functional canonical correlation analysis as a special case when only two sets of functions are considered. As in classical multiple-set canonical correlation analysis, computationally, the…

Managing adaptively for multifunctionality in agricultural systems

USGS Publications Warehouse

Hodbod, Jennifer; Barreteau, Olivier; Allen, Craig R.; Magda, Danièle

2016-01-01

The critical importance of agricultural systems for food security and as a dominant global landcover requires management that considers the full dimensions of system functions at appropriate scales, i.e. multifunctionality. We propose that adaptive management is the most suitable management approach for such goals, given its ability to reduce uncertainty over time and support multiple objectives within a system, for multiple actors. As such, adaptive management may be the most appropriate method for sustainably intensifying production whilst increasing the quantity and quality of ecosystem services. However, the current assessment of performance of agricultural systems doesn’t reward ecosystem service provision. Therefore, we present an overview of the ecosystem functions agricultural systems should and could provide, coupled with a revised definition for assessing the performance of agricultural systems from a multifunctional perspective that, when all satisfied, would create adaptive agricultural systems that can increase production whilst ensuring food security and the quantity and quality of ecosystem services. The outcome of this high level of performance is the capacity to respond to multiple shocks without collapse, equity and triple bottom line sustainability. Through the assessment of case studies, we find that alternatives to industrialized agricultural systems incorporate more functional goals, but that there are mixed findings as to whether these goals translate into positive measurable outcomes. We suggest that an adaptive management perspective would support the implementation of a systematic analysis of the social, ecological and economic trade-offs occurring within such systems, particularly between ecosystem services and functions, in order to provide suitable and comparable assessments. We also identify indicators to monitor performance at multiple scales in agricultural systems which can be used within an adaptive management framework to increase resilience at multiple scales.

Managing adaptively for multifunctionality in agricultural systems.

PubMed

Hodbod, Jennifer; Barreteau, Olivier; Allen, Craig; Magda, Danièle

2016-12-01

The critical importance of agricultural systems for food security and as a dominant global landcover requires management that considers the full dimensions of system functions at appropriate scales, i.e. multifunctionality. We propose that adaptive management is the most suitable management approach for such goals, given its ability to reduce uncertainty over time and support multiple objectives within a system, for multiple actors. As such, adaptive management may be the most appropriate method for sustainably intensifying production whilst increasing the quantity and quality of ecosystem services. However, the current assessment of performance of agricultural systems doesn't reward ecosystem service provision. Therefore, we present an overview of the ecosystem functions agricultural systems should and could provide, coupled with a revised definition for assessing the performance of agricultural systems from a multifunctional perspective that, when all satisfied, would create adaptive agricultural systems that can increase production whilst ensuring food security and the quantity and quality of ecosystem services. The outcome of this high level of performance is the capacity to respond to multiple shocks without collapse, equity and triple bottom line sustainability. Through the assessment of case studies, we find that alternatives to industrialized agricultural systems incorporate more functional goals, but that there are mixed findings as to whether these goals translate into positive measurable outcomes. We suggest that an adaptive management perspective would support the implementation of a systematic analysis of the social, ecological and economic trade-offs occurring within such systems, particularly between ecosystem services and functions, in order to provide suitable and comparable assessments. We also identify indicators to monitor performance at multiple scales in agricultural systems which can be used within an adaptive management framework to increase resilience at multiple scales. Copyright © 2016 Elsevier Ltd. All rights reserved.

The SLP-76 Src homology 2 domain is required for T cell development and activation.

PubMed

Burns, Jeremy C; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A; Kliche, Stefanie; Jordan, Martha S

2011-11-01

The adapter protein Src homology 2 (SH2) domain-containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adapter proteins that function together to activate second messengers required for TCR signal propagation. The N terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with ADAP and HPK1. Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production, and phosphorylation of protein kinase D and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells.

Forging our understanding of lncRNAs in the brain.

PubMed

Andersen, Rebecca E; Lim, Daniel A

2018-01-01

During both development and adulthood, the human brain expresses many thousands of long noncoding RNAs (lncRNAs), and aberrant lncRNA expression has been associated with a wide range of neurological diseases. Although the biological significance of most lncRNAs remains to be discovered, it is now clear that certain lncRNAs carry out important functions in neurodevelopment, neural cell function, and perhaps even diseases of the human brain. Given the relatively inclusive definition of lncRNAs-transcripts longer than 200 nucleotides with essentially no protein coding potential-this class of noncoding transcript is both large and very diverse. Furthermore, emerging data indicate that lncRNA genes can act via multiple, non-mutually exclusive molecular mechanisms, and specific functions are difficult to predict from lncRNA expression or sequence alone. Thus, the different experimental approaches used to explore the role of a lncRNA might each shed light upon distinct facets of its overall molecular mechanism, and combining multiple approaches may be necessary to fully illuminate the function of any particular lncRNA. To understand how lncRNAs affect brain development and neurological disease, in vivo studies of lncRNA function are required. Thus, in this review, we focus our discussion upon a small set of neural lncRNAs that have been experimentally manipulated in mice. Together, these examples illustrate how studies of individual lncRNAs using multiple experimental approaches can help reveal the richness and complexity of lncRNA function in both neurodevelopment and diseases of the brain.

Visualization and Measurement of Multiple Components of the Autophagy Flux.

PubMed

Evans, Tracey; Button, Robert; Anichtchik, Oleg; Luo, Shouqing

2018-06-24

Autophagy is an intracellular degradation process that mediates the clearance of cytoplasmic components. As well as being an important function for cellular homeostasis, autophagy also promotes the removal of aberrant protein accumulations, such as those seen in conditions like neurodegeneration. The dynamic nature of autophagy requires precise methods to examine the process at multiple stages. The protocols described herein enable the dissection of the complete autophagy process (the "autophagy flux"). These allow for the elucidation of which stages of autophagy may be altered in response to various diseases and treatments.

Mammalian Polyamine Metabolism and Function

PubMed Central

Pegg, Anthony E.

2009-01-01

Summary Polyamines are ubiquitous small basic molecules that play multiple essential roles in mammalian physiology. Their cellular content is highly regulated and there is convincing evidence that altered metabolism is involvement in many disease states. Drugs altering polyamine levels may therefore have a variety of important targets. This review will summarize the current state of understanding of polyamine metabolism and function, the regulation of polyamine content, and heritable pathological conditions that may be derived from altered polyamine metabolism. PMID:19603518

Estimating Commute Distances of U.S. Army Reservists by Regional and Unit Characteristics

DTIC Science & Technology

1990-09-01

multiple regression equation is used to estimate the parameters of the commute distance distribution as a function of reserve center and market ...used to estimate the parameters of the commute distance distribution as a function of reserve center and market characteristics. The results of the...recruiting personnel to meet unit fill rates. An important objective of the USAREC is to identify market areas that will support new reserve units [Ref. 2:p

Multiple effects of hydrological connectivity on floodplain processes in human modified river systems

NASA Astrophysics Data System (ADS)

Hein, Thomas; Bondar-Kunze, Elisabeth; Preiner, Stefan; Reckendorfer, Walter; Tritthart, Michael; Weigelhofer, Gabriele; Welti, Nina

2014-05-01

Floodplain and riparian ecosystems provide multiple functions and services of importance for human well-being and are of strategic importance for different sectors at catchment scale. Especially floodplains in the vicinity of urban areas can be areas of conflicting interests ranging from different land use types, flood water retention, drinking water production and recreation to conservation of last remnants of former riverine landscape, as it is the case in floodplains in the Danube Nationalpark downstream Vienna. Many of these ecosystem functions and services are controlled by the exchange conditions between river main channel and floodplain systems, the hydrological connectivity. At the same time these systems have been highly altered and especially the connectivity has been severely impaired. Thus, far ranging effects of changes in hydrological connectivity at various levels can be expected in altered floodplain systems. The aim of this presentation is to explore the complex control of different ecosystem functions and associated services by different parameters of hydrological connectivity, ranging from nutrient, sediment and matter dynamics and biodiversity aspects. Increasing connectivity will be shown to impact microbial dynamics, sediment-water interactions, carbon dynamics and trophic conditions, thus affecting the fundamental functions of particular floodplain systems at various spatial and temporal scales. Based on these changes also the provision of ecosystem services of floodplains is affected. The results clearly show that hydrological connectivity needs to be considered in a sustainable management approach.

SVM-Prot 2016: A Web-Server for Machine Learning Prediction of Protein Functional Families from Sequence Irrespective of Similarity.

PubMed

Li, Ying Hong; Xu, Jing Yu; Tao, Lin; Li, Xiao Feng; Li, Shuang; Zeng, Xian; Chen, Shang Ying; Zhang, Peng; Qin, Chu; Zhang, Cheng; Chen, Zhe; Zhu, Feng; Chen, Yu Zong

2016-01-01

Knowledge of protein function is important for biological, medical and therapeutic studies, but many proteins are still unknown in function. There is a need for more improved functional prediction methods. Our SVM-Prot web-server employed a machine learning method for predicting protein functional families from protein sequences irrespective of similarity, which complemented those similarity-based and other methods in predicting diverse classes of proteins including the distantly-related proteins and homologous proteins of different functions. Since its publication in 2003, we made major improvements to SVM-Prot with (1) expanded coverage from 54 to 192 functional families, (2) more diverse protein descriptors protein representation, (3) improved predictive performances due to the use of more enriched training datasets and more variety of protein descriptors, (4) newly integrated BLAST analysis option for assessing proteins in the SVM-Prot predicted functional families that were similar in sequence to a query protein, and (5) newly added batch submission option for supporting the classification of multiple proteins. Moreover, 2 more machine learning approaches, K nearest neighbor and probabilistic neural networks, were added for facilitating collective assessment of protein functions by multiple methods. SVM-Prot can be accessed at http://bidd2.nus.edu.sg/cgi-bin/svmprot/svmprot.cgi.

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

Reelin promotes the adhesion and drug resistance of multiple myeloma cells via integrin β1 signaling and STAT3

PubMed Central

Lv, Meng; Liang, Xiaodong; Dai, Hui; Qin, Xiaodan; Zhang, Yan; Hao, Jie; Sun, Xiuyuan; Yin, Yanhui; Huang, Xiaojun; Zhang, Jun; Lu, Jin; Ge, Qing

2016-01-01

Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of α5β1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-β1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis. PMID:26848618

Reelin promotes the adhesion and drug resistance of multiple myeloma cells via integrin β1 signaling and STAT3.

PubMed

Lin, Liang; Yan, Fan; Zhao, Dandan; Lv, Meng; Liang, Xiaodong; Dai, Hui; Qin, Xiaodan; Zhang, Yan; Hao, Jie; Sun, Xiuyuan; Yin, Yanhui; Huang, Xiaojun; Zhang, Jun; Lu, Jin; Ge, Qing

2016-03-01

Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of α5β1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-β1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis.

Multi-criteria decision aid approach for the selection of the best compromise management scheme for ELVs: the case of Cyprus.

PubMed

Mergias, I; Moustakas, K; Papadopoulos, A; Loizidou, M

2007-08-25

Each alternative scheme for treating a vehicle at its end of life has its own consequences from a social, environmental, economic and technical point of view. Furthermore, the criteria used to determine these consequences are often contradictory and not equally important. In the presence of multiple conflicting criteria, an optimal alternative scheme never exists. A multiple-criteria decision aid (MCDA) method to aid the Decision Maker (DM) in selecting the best compromise scheme for the management of End-of-Life Vehicles (ELVs) is presented in this paper. The constitution of a set of alternatives schemes, the selection of a list of relevant criteria to evaluate these alternative schemes and the choice of an appropriate management system are also analyzed in this framework. The proposed procedure relies on the PROMETHEE method which belongs to the well-known family of multiple criteria outranking methods. For this purpose, level, linear and Gaussian functions are used as preference functions.

Variant-aware saturating mutagenesis using multiple Cas9 nucleases identifies regulatory elements at trait-associated loci.

PubMed

Canver, Matthew C; Lessard, Samuel; Pinello, Luca; Wu, Yuxuan; Ilboudo, Yann; Stern, Emily N; Needleman, Austen J; Galactéros, Frédéric; Brugnara, Carlo; Kutlar, Abdullah; McKenzie, Colin; Reid, Marvin; Chen, Diane D; Das, Partha Pratim; A Cole, Mitchel; Zeng, Jing; Kurita, Ryo; Nakamura, Yukio; Yuan, Guo-Cheng; Lettre, Guillaume; Bauer, Daniel E; Orkin, Stuart H

2017-04-01

Cas9-mediated, high-throughput, saturating in situ mutagenesis permits fine-mapping of function across genomic segments. Disease- and trait-associated variants identified in genome-wide association studies largely cluster at regulatory loci. Here we demonstrate the use of multiple designer nucleases and variant-aware library design to interrogate trait-associated regulatory DNA at high resolution. We developed a computational tool for the creation of saturating-mutagenesis libraries with single or multiple nucleases with incorporation of variants. We applied this methodology to the HBS1L-MYB intergenic region, which is associated with red-blood-cell traits, including fetal hemoglobin levels. This approach identified putative regulatory elements that control MYB expression. Analysis of genomic copy number highlighted potential false-positive regions, thus emphasizing the importance of off-target analysis in the design of saturating-mutagenesis experiments. Together, these data establish a widely applicable high-throughput and high-resolution methodology to identify minimal functional sequences within large disease- and trait-associated regions.

Both cis and trans Activities of Foot-and-Mouth Disease Virus 3D Polymerase Are Essential for Viral RNA Replication.

PubMed

Herod, Morgan R; Ferrer-Orta, Cristina; Loundras, Eleni-Anna; Ward, Joseph C; Verdaguer, Nuria; Rowlands, David J; Stonehouse, Nicola J

2016-08-01

The Picornaviridae is a large family of positive-sense RNA viruses that contains numerous human and animal pathogens, including foot-and-mouth disease virus (FMDV). The picornavirus replication complex comprises a coordinated network of protein-protein and protein-RNA interactions involving multiple viral and host-cellular factors. Many of the proteins within the complex possess multiple roles in viral RNA replication, some of which can be provided in trans (i.e., via expression from a separate RNA molecule), while others are required in cis (i.e., expressed from the template RNA molecule). In vitro studies have suggested that multiple copies of the RNA-dependent RNA polymerase (RdRp) 3D are involved in the viral replication complex. However, it is not clear whether all these molecules are catalytically active or what other function(s) they provide. In this study, we aimed to distinguish between catalytically active 3D molecules and those that build a replication complex. We report a novel nonenzymatic cis-acting function of 3D that is essential for viral-genome replication. Using an FMDV replicon in complementation experiments, our data demonstrate that this cis-acting role of 3D is distinct from the catalytic activity, which is predominantly trans acting. Immunofluorescence studies suggest that both cis- and trans-acting 3D molecules localize to the same cellular compartment. However, our genetic and structural data suggest that 3D interacts in cis with RNA stem-loops that are essential for viral RNA replication. This study identifies a previously undescribed aspect of picornavirus replication complex structure-function and an important methodology for probing such interactions further. Foot-and-mouth disease virus (FMDV) is an important animal pathogen responsible for foot-and-mouth disease. The disease is endemic in many parts of the world with outbreaks within livestock resulting in major economic losses. Propagation of the viral genome occurs within replication complexes, and understanding this process can facilitate the development of novel therapeutic strategies. Many of the nonstructural proteins involved in replication possess multiple functions in the viral life cycle, some of which can be supplied to the replication complex from a separate genome (i.e., in trans) while others must originate from the template (i.e., in cis). Here, we present an analysis of cis and trans activities of the RNA-dependent RNA polymerase 3D. We demonstrate a novel cis-acting role of 3D in replication. Our data suggest that this role is distinct from its enzymatic functions and requires interaction with the viral genome. Our data further the understanding of genome replication of this important pathogen. Copyright © 2016 Herod et al.

A pilot study on factors involved with work participation in the early stages of multiple sclerosis.

PubMed

Van der Hiele, Karin; Middelkoop, Huub A M; Ruimschotel, Rob; Kamminga, Noëlle G A; Visser, Leo H

2014-01-01

Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation. To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job. Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years. Patients with a paid job (57%) reported better physical functioning (p<0.001), better memory functioning (p = 0.01) and a lower physical impact of fatigue (p = 0.018) than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005) and a lower social impact of fatigue (r =  -0.46, p = 0.029) correlated with an increased number of working hours. Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS.

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases.

PubMed

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

What Specific Facets of Executive Function are Associated with Academic Functioning in Youth with Attention-Deficit/Hyperactivity Disorder?

PubMed Central

Langberg, Joshua M.; Dvorsky, Melissa R.; Evans, Steven W.

2013-01-01

The purpose of the study was to evaluate the relation between ratings of Executive Function (EF) and academic functioning in a sample of 94 middle-school-aged youth with Attention-Deficit/Hyperactivity Disorder (ADHD; Mage = 11.9; 78% male; 21% minority). This study builds on prior work by evaluating associations between multiple specific aspects of EF (e.g., working memory, inhibition, and planning and organization) as rated by both parents and teachers on the Behavior Rating Inventory of Executive Function (BRIEF), with multiple academic outcomes, including school grades and homework problems. Further, this study examined the relationship between EF and academic outcomes above and beyond ADHD symptoms and controlled for a number of potentially important covariates, including intelligence and achievement scores. The EF Planning and Organization subscale as rated by both parents and teachers predicted school grades above and beyond symptoms of ADHD and relevant covariates. Parent ratings of youth’s ability to transition effectively between tasks/situations (Shift subscale) also predicted school grades. Parent-rated symptoms of inattention, hyperactivity/impulsivity, and planning and organization abilities were significant in the final model predicting homework problems. In contrast, only symptoms of inattention and the Organization of Materials subscale from the BRIEF were significant in the teacher model predicting homework problems. Organization and planning abilities are highly important aspects academic functioning for middle-school-aged youth with ADHD. Implications of these findings for the measurement of EF, and organization and planning abilities in particular, are discussed along with potential implications for intervention. PMID:23640285

Nitrogen Cycle Evaluation (NiCE) Chip for the Simultaneous Analysis of Multiple N-Cycle Associated Genes.

PubMed

Oshiki, Mamoru; Segawa, Takahiro; Ishii, Satoshi

2018-02-02

Various microorganisms play key roles in the Nitrogen (N) cycle. Quantitative PCR (qPCR) and PCR-amplicon sequencing of the N cycle functional genes allow us to analyze the abundance and diversity of microbes responsible in the N transforming reactions in various environmental samples. However, analysis of multiple target genes can be cumbersome and expensive. PCR-independent analysis, such as metagenomics and metatranscriptomics, is useful but expensive especially when we analyze multiple samples and try to detect N cycle functional genes present at relatively low abundance. Here, we present the application of microfluidic qPCR chip technology to simultaneously quantify and prepare amplicon sequence libraries for multiple N cycle functional genes as well as taxon-specific 16S rRNA gene markers for many samples. This approach, named as N cycle evaluation (NiCE) chip, was evaluated by using DNA from pure and artificially mixed bacterial cultures and by comparing the results with those obtained by conventional qPCR and amplicon sequencing methods. Quantitative results obtained by the NiCE chip were comparable to those obtained by conventional qPCR. In addition, the NiCE chip was successfully applied to examine abundance and diversity of N cycle functional genes in wastewater samples. Although non-specific amplification was detected on the NiCE chip, this could be overcome by optimizing the primer sequences in the future. As the NiCE chip can provide high-throughput format to quantify and prepare sequence libraries for multiple N cycle functional genes, this tool should advance our ability to explore N cycling in various samples. Importance. We report a novel approach, namely Nitrogen Cycle Evaluation (NiCE) chip by using microfluidic qPCR chip technology. By sequencing the amplicons recovered from the NiCE chip, we can assess diversities of the N cycle functional genes. The NiCE chip technology is applicable to analyze the temporal dynamics of the N cycle gene transcriptions in wastewater treatment bioreactors. The NiCE chip can provide high-throughput format to quantify and prepare sequence libraries for multiple N cycle functional genes. While there is a room for future improvement, this tool should significantly advance our ability to explore the N cycle in various environmental samples. Copyright © 2018 American Society for Microbiology.

Treatment of multiple synchronous misdiagnosed renal cell cancers in a young patient affected by a "de novo" Von Hippel-Lindau syndrome.

PubMed

Allasia, Marco; Battaglia, Antonino; Pasini, Barbara; Gazzera, Carlo; Calandri, Marco; Bosio, Andrea; Gontero, Paolo; Destefanis, Paolo

2017-02-28

Von Hippel-Lindau (VHL) disease is an autosomal dominant inherited syndrome occurring in one out of 36,000 live births. Diagnosis could be a challenge in patients with no familial VHL history. Renal cancer (RCC) represents one of the most important manifestations. RCC is usually recurrent and multifocal. Actually treating RCC in VHL patients represent a clinical dilemma: the oncological outcomes must be balanced against renal function preservation. A young man with a negative familial history was referred to our department with seven misdiagnosed renal masses. VHL disease was determined through genetic test. The multiple RCCs were treated by surgery and percutaneous thermal ablation by radiofrequency ablation (RFA) with complete control of RCC and no impairment of renal function. This case history confirms that VHL disease has to be suspected in young patients with evidence of synchronous multiple renal masses and in presence of specific clinical criteria.RFA appears to be safe in terms of oncological radicalism and in renal function preservation.In hereditary RCC, we should purpose, whenever it is possible, minimally invasive treatment in terms of low hospital stay and a minimal loss of renal tissue.

Diversity Performance Analysis on Multiple HAP Networks

PubMed Central

Dong, Feihong; Li, Min; Gong, Xiangwu; Li, Hongjun; Gao, Fengyue

2015-01-01

One of the main design challenges in wireless sensor networks (WSNs) is achieving a high-data-rate transmission for individual sensor devices. The high altitude platform (HAP) is an important communication relay platform for WSNs and next-generation wireless networks. Multiple-input multiple-output (MIMO) techniques provide the diversity and multiplexing gain, which can improve the network performance effectively. In this paper, a virtual MIMO (V-MIMO) model is proposed by networking multiple HAPs with the concept of multiple assets in view (MAV). In a shadowed Rician fading channel, the diversity performance is investigated. The probability density function (PDF) and cumulative distribution function (CDF) of the received signal-to-noise ratio (SNR) are derived. In addition, the average symbol error rate (ASER) with BPSK and QPSK is given for the V-MIMO model. The system capacity is studied for both perfect channel state information (CSI) and unknown CSI individually. The ergodic capacity with various SNR and Rician factors for different network configurations is also analyzed. The simulation results validate the effectiveness of the performance analysis. It is shown that the performance of the HAPs network in WSNs can be significantly improved by utilizing the MAV to achieve overlapping coverage, with the help of the V-MIMO techniques. PMID:26134102

Understanding cognitive dysfunction in multiple sclerosis: integrating a first-person perspective with neuropsychological testing, neuroimaging, and cognitive neuroscience research.

PubMed

Courtney, Susan M

2011-12-01

This paper gives perspectives on a companion article, the case history of a professional writer who has multiple sclerosis. The patient's first-person account of her illness is combined with clinical summaries about her care. The discussion of this case illustrates the value of combining such subjective and objective reports in evaluating a patient. Furthermore, considering these reports in the context of current research findings on the organization and function of cognitive neural systems can shed light on patients' seemingly contradictory clinical findings. For this patient, a deficit in the ability to select the most important information to achieve her current goals reflected her neuropsychological test results and neuroradiologic findings, and helped to explain her difficulties with her job and her activities of daily living. Because the patient's cognitive impairments have been her primary manifestations of multiple sclerosis, she illustrates the importance of physicians attending to and helping patients manage their cognitive deficits.

Alternative Splicing of sept9a and sept9b in Zebrafish Produces Multiple mRNA Transcripts Expressed Throughout Development

PubMed Central

Hannibal, Mark C.; Kimelman, David

2010-01-01

Background Septins are involved in a number of cellular processes including cytokinesis and organization of the cytoskeleton. Alterations in human septin-9 (SEPT9) levels have been linked to multiple cancers, whereas mutations in SEPT9 cause the episodic neuropathy, hereditary neuralgic amyotrophy (HNA). Despite its important function in human health, the in vivo role of SEPT9 is unknown. Methodology/Principal Findings Here we utilize zebrafish to study the role of SEPT9 in early development. We show that zebrafish possess two genes, sept9a and sept9b that, like humans, express multiple transcripts. Knockdown or overexpression of sept9a transcripts results in specific developmental alterations including circulation defects and aberrant epidermal development. Conclusions/Significance Our work demonstrates that sept9 plays an important role in zebrafish development, and establishes zebrafish as a valuable model organism for the study of SEPT9. PMID:20502708

Lung function and exhaled nitric oxide in healthy unsedated African infants

PubMed Central

Gray, Diane; Willemse, Lauren; Visagie, Ane; Smith, Emilee; Czövek, Dorottya; Sly, Peter D; Hantos, Zoltán; Hall, Graham L; Zar, Heather J

2015-01-01

Background and objective Population-appropriate lung function reference data are essential to accurately identify respiratory disease and measure response to interventions. There are currently no reference data in African infants. The aim was to describe normal lung function in healthy African infants. Methods Lung function was performed on healthy South African infants enrolled in a birth cohort study, the Drakenstein child health study. Infants were excluded if they were born preterm or had a history of neonatal respiratory distress or prior respiratory tract infection. Measurements, made during natural sleep, included the forced oscillation technique, tidal breathing, exhaled nitric oxide and multiple breath washout measures. Results Three hundred sixty-three infants were tested. Acceptable and repeatable measurements were obtained in 356 (98%) and 352 (97%) infants for tidal breathing analysis and exhaled nitric oxide outcomes, 345 (95%) infants for multiple breath washout and 293 of the 333 (88%) infants for the forced oscillation technique. Age, sex and weight-for-age z score were significantly associated with lung function measures. Conclusions This study provides reference data for unsedated infant lung function in African infants and highlights the importance of using population-specific data. PMID:26134556

Diversity Enhances NPP, N Retention, and Soil Microbial Diversity in Experimental Urban Grassland Assemblages

PubMed Central

Thompson, Grant L.; Kao-Kniffin, Jenny

2016-01-01

Urban grasslands, landscapes dominated by turfgrasses for aesthetic or recreational groundcovers, are rapidly expanding in the United States and globally. These managed ecosystems are often less diverse than the natural or agricultural lands they replace, leading to potential losses in ecosystem functioning. Research in non-urban systems has provided evidence for increases in multiple ecosystem functions associated with greater plant diversity. To test if biodiversity-ecosystem function findings are applicable to urban grasslands, we examined the effect of plant species and genotypic diversity on three ecosystem functions, using grassland assemblages of increasing diversity that were grown within a controlled environment facility. We found positive effects of plant diversity on reduced nitrate leaching and plant productivity. Soil microbial diversity (Mean Shannon Diversity, H’) of bacteria and fungi were also enhanced in multi-species plantings, suggesting that moderate increments in plant diversity influence the composition of soil biota. The results from this study indicate that plant diversity impacts multiple functions that are important in urban ecosystems; therefore, further tests of urban grassland biodiversity should be examined in situ to determine the feasibility of manipulating plant diversity as an explicit landscape design and function trait. PMID:27243768

Annotating Protein Functional Residues by Coupling High-Throughput Fitness Profile and Homologous-Structure Analysis

PubMed Central

Du, Yushen; Wu, Nicholas C.; Jiang, Lin; Zhang, Tianhao; Gong, Danyang; Shu, Sara; Wu, Ting-Ting

2016-01-01

ABSTRACT Identification and annotation of functional residues are fundamental questions in protein sequence analysis. Sequence and structure conservation provides valuable information to tackle these questions. It is, however, limited by the incomplete sampling of sequence space in natural evolution. Moreover, proteins often have multiple functions, with overlapping sequences that present challenges to accurate annotation of the exact functions of individual residues by conservation-based methods. Using the influenza A virus PB1 protein as an example, we developed a method to systematically identify and annotate functional residues. We used saturation mutagenesis and high-throughput sequencing to measure the replication capacity of single nucleotide mutations across the entire PB1 protein. After predicting protein stability upon mutations, we identified functional PB1 residues that are essential for viral replication. To further annotate the functional residues important to the canonical or noncanonical functions of viral RNA-dependent RNA polymerase (vRdRp), we performed a homologous-structure analysis with 16 different vRdRp structures. We achieved high sensitivity in annotating the known canonical polymerase functional residues. Moreover, we identified a cluster of noncanonical functional residues located in the loop region of the PB1 β-ribbon. We further demonstrated that these residues were important for PB1 protein nuclear import through the interaction with Ran-binding protein 5. In summary, we developed a systematic and sensitive method to identify and annotate functional residues that are not restrained by sequence conservation. Importantly, this method is generally applicable to other proteins about which homologous-structure information is available. PMID:27803181

Multiple Deficits in ADHD: Executive Dysfunction, Delay Aversion, Reaction Time Variability, and Emotional Deficits

ERIC Educational Resources Information Center

Sjowall, Douglas; Roth, Linda; Lindqvist, Sofia; Thorell, Lisa B.

2013-01-01

Background: The notion that ADHD constitutes a heterogeneous disorder is well accepted. However, this study contributes with new important knowledge by examining independent effects of a large range of neuropsychological deficits. In addition, the study investigated whether deficits in emotional functioning constitute a dissociable component of…

Multiple loss-of-function 5-O-Glucosyltransferase alleles revealed in Vitis vinifera, but not in other Vitis species

USDA-ARS?s Scientific Manuscript database

Anthocyanins in red grapes (Vitis genus) are important components of wine and beneficial to human health. These antioxidant compounds are present in two glycosylation states: monoglucoside (3-O-glucoside) and diglucoside (3, 5-di-O-glucoside). While monoglucoside anthocyanins are present in all pigm...

Resilient Transportation Systems in a Post-Disaster Environment: A Case Study of Opportunities Realized and Missed in New Orleans and the Louisiana Coastal Region

DOT National Transportation Integrated Search

2010-10-01

Based upon our research in Post-Katrina New Orleans, we define transportation resiliency as a systems ability to function before, during and after major disruptions through reliance upon multiple mobility options. The importance of a resilient tra...

Free energy landscape and transition pathways from Watson–Crick to Hoogsteen base pairing in free duplex DNA

PubMed Central

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-01-01

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson–Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine–thymine (A–T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. PMID:26250116

Higher biodiversity is required to sustain multiple ecosystem processes across temperature regimes

PubMed Central

Perkins, Daniel M; Bailey, R A; Dossena, Matteo; Gamfeldt, Lars; Reiss, Julia; Trimmer, Mark; Woodward, Guy

2015-01-01

Biodiversity loss is occurring rapidly worldwide, yet it is uncertain whether few or many species are required to sustain ecosystem functioning in the face of environmental change. The importance of biodiversity might be enhanced when multiple ecosystem processes (termed multifunctionality) and environmental contexts are considered, yet no studies have quantified this explicitly to date. We measured five key processes and their combined multifunctionality at three temperatures (5, 10 and 15 °C) in freshwater aquaria containing different animal assemblages (1–4 benthic macroinvertebrate species). For single processes, biodiversity effects were weak and were best predicted by additive-based models, i.e. polyculture performances represented the sum of their monoculture parts. There were, however, significant effects of biodiversity on multifunctionality at the low and the high (but not the intermediate) temperature. Variation in the contribution of species to processes across temperatures meant that greater biodiversity was required to sustain multifunctionality across different temperatures than was the case for single processes. This suggests that previous studies might have underestimated the importance of biodiversity in sustaining ecosystem functioning in a changing environment. PMID:25131335

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed Central

Prossnitz, Eric R.; Hathaway, Helen J.

2015-01-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. PMID:26189910

[Infection control team (ICT) in cooperation with microbiology laboratories].

PubMed

Okazaki, Mitsuhiro

2012-10-01

Infection control as a medical safety measure is an important issue in all medical facilities. In order to tackle this measure, cooperation between the infection control team (ICT) and microbiological laboratory is indispensable. Multiple drug-resistant bacteria have shifted from Gram-positive bacteria to Gram-negative bacilli within the last ten years. There are also a variety of bacilli, complicating the examination method and test results further. Therefore, cooperation between the ICT and microbiological laboratory has become important to understand examination results and to use them. In order to maintain functional cooperation, explanatory and communicative ability between the microbiological laboratory and ICT is required every day. Such positive information exchange will develop into efficient and functional ICT activity.

Rad5, HLTF, and SHPRH: A Fresh View of an Old Story.

PubMed

Elserafy, Menattallah; Abugable, Arwa A; Atteya, Reham; El-Khamisy, Sherif F

2018-05-25

Not only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Egg Case Silk Gene Sequences from Argiope Spiders: Evidence for Multiple Loci and a Loss of Function Between Paralogs

PubMed Central

Chaw, R. Crystal; Collin, Matthew; Wimmer, Marjorie; Helmrick, Kara-Leigh; Hayashi, Cheryl Y.

2017-01-01

Spiders swath their eggs with silk to protect developing embryos and hatchlings. Egg case silks, like other fibrous spider silks, are primarily composed of proteins called spidroins (spidroin = spider-fibroin). Silks, and thus spidroins, are important throughout the lives of spiders, yet the evolution of spidroin genes has been relatively understudied. Spidroin genes are notoriously difficult to sequence because they are typically very long (≥ 10 kb of coding sequence) and highly repetitive. Here, we investigate the evolution of spider silk genes through long-read sequencing of Bacterial Artificial Chromosome (BAC) clones. We demonstrate that the silver garden spider Argiope argentata has multiple egg case spidroin loci with a loss of function at one locus. We also use degenerate PCR primers to search the genomic DNA of congeneric species and find evidence for multiple egg case spidroin loci in other Argiope spiders. Comparative analyses show that these multiple loci are more similar at the nucleotide level within a species than between species. This pattern is consistent with concerted evolution homogenizing gene copies within a genome. More complicated explanations include convergent evolution or recent independent gene duplications within each species. PMID:29127108

Structural Refinement of Proteins by Restrained Molecular Dynamics Simulations with Non-interacting Molecular Fragments.

PubMed

Shen, Rong; Han, Wei; Fiorin, Giacomo; Islam, Shahidul M; Schulten, Klaus; Roux, Benoît

2015-10-01

The knowledge of multiple conformational states is a prerequisite to understand the function of membrane transport proteins. Unfortunately, the determination of detailed atomic structures for all these functionally important conformational states with conventional high-resolution approaches is often difficult and unsuccessful. In some cases, biophysical and biochemical approaches can provide important complementary structural information that can be exploited with the help of advanced computational methods to derive structural models of specific conformational states. In particular, functional and spectroscopic measurements in combination with site-directed mutations constitute one important source of information to obtain these mixed-resolution structural models. A very common problem with this strategy, however, is the difficulty to simultaneously integrate all the information from multiple independent experiments involving different mutations or chemical labels to derive a unique structural model consistent with the data. To resolve this issue, a novel restrained molecular dynamics structural refinement method is developed to simultaneously incorporate multiple experimentally determined constraints (e.g., engineered metal bridges or spin-labels), each treated as an individual molecular fragment with all atomic details. The internal structure of each of the molecular fragments is treated realistically, while there is no interaction between different molecular fragments to avoid unphysical steric clashes. The information from all the molecular fragments is exploited simultaneously to constrain the backbone to refine a three-dimensional model of the conformational state of the protein. The method is illustrated by refining the structure of the voltage-sensing domain (VSD) of the Kv1.2 potassium channel in the resting state and by exploring the distance histograms between spin-labels attached to T4 lysozyme. The resulting VSD structures are in good agreement with the consensus model of the resting state VSD and the spin-spin distance histograms from ESR/DEER experiments on T4 lysozyme are accurately reproduced.

Distributed patterns of activity in sensory cortex reflect the precision of multiple items maintained in visual short-term memory.

PubMed

Emrich, Stephen M; Riggall, Adam C; Larocque, Joshua J; Postle, Bradley R

2013-04-10

Traditionally, load sensitivity of sustained, elevated activity has been taken as an index of storage for a limited number of items in visual short-term memory (VSTM). Recently, studies have demonstrated that the contents of a single item held in VSTM can be decoded from early visual cortex, despite the fact that these areas do not exhibit elevated, sustained activity. It is unknown, however, whether the patterns of neural activity decoded from sensory cortex change as a function of load, as one would expect from a region storing multiple representations. Here, we use multivoxel pattern analysis to examine the neural representations of VSTM in humans across multiple memory loads. In an important extension of previous findings, our results demonstrate that the contents of VSTM can be decoded from areas that exhibit a transient response to visual stimuli, but not from regions that exhibit elevated, sustained load-sensitive delay-period activity. Moreover, the neural information present in these transiently activated areas decreases significantly with increasing load, indicating load sensitivity of the patterns of activity that support VSTM maintenance. Importantly, the decrease in classification performance as a function of load is correlated with within-subject changes in mnemonic resolution. These findings indicate that distributed patterns of neural activity in putatively sensory visual cortex support the representation and precision of information in VSTM.

Masticatory performance and oral health-related quality of life before and after complete denture treatment.

PubMed

Yamamoto, Saori; Shiga, Hiroshi

2018-03-13

To clarify the relationship between masticatory performance and oral health-related quality of life (OHRQoL) before and after complete denture treatment. Thirty patients wearing complete dentures were asked to chew a gummy jelly on their habitual chewing side, and the amount of glucose extraction during chewing was measured as the parameter of masticatory performance. Subjects were asked to answer the Oral Health Impact Profile (OHIP-J49) questionnaire, which consists of 49 questions related to oral problems. The total score of 49 question items along with individual domain scores within the seven domains (functional limitation, pain, psychological discomfort, physical disability, psychological disability, social disability and handicap) were calculated and used as the parameters of OHRQoL. These records were obtained before treatment and 3 months after treatment. Each parameter of masticatory performance and OHRQoL was compared before treatment and after treatment. The relationship between masticatory performance and OHRQoL was investigated, and a stepwise multiple linear regression analysis was performed. Both masticatory performance and OHRQoL were significantly improved after treatment. Furthermore, masticatory performance was significantly correlated with some parameters of OHRQoL. The stepwise multiple linear regression analysis showed functional limitation and pain as important factors affecting masticatory performance before treatment and functional limitation as important factors affecting masticatory performance after treatment. These results suggested that masticatory performance and OHRQoL are significantly improved after treatment and that there is a close relationship between the two. Moreover, functional limitation was found to be the most important factor affecting masticatory performance. Copyright © 2018 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Temporal Drivers of Liking Based on Functional Data Analysis and Non-Additive Models for Multi-Attribute Time-Intensity Data of Fruit Chews.

PubMed

Kuesten, Carla; Bi, Jian

2018-06-03

Conventional drivers of liking analysis was extended with a time dimension into temporal drivers of liking (TDOL) based on functional data analysis methodology and non-additive models for multiple-attribute time-intensity (MATI) data. The non-additive models, which consider both direct effects and interaction effects of attributes to consumer overall liking, include Choquet integral and fuzzy measure in the multi-criteria decision-making, and linear regression based on variance decomposition. Dynamics of TDOL, i.e., the derivatives of the relative importance functional curves were also explored. Well-established R packages 'fda', 'kappalab' and 'relaimpo' were used in the paper for developing TDOL. Applied use of these methods shows that the relative importance of MATI curves offers insights for understanding the temporal aspects of consumer liking for fruit chews.

FunGene: the functional gene pipeline and repository.

PubMed

Fish, Jordan A; Chai, Benli; Wang, Qiong; Sun, Yanni; Brown, C Titus; Tiedje, James M; Cole, James R

2013-01-01

Ribosomal RNA genes have become the standard molecular markers for microbial community analysis for good reasons, including universal occurrence in cellular organisms, availability of large databases, and ease of rRNA gene region amplification and analysis. As markers, however, rRNA genes have some significant limitations. The rRNA genes are often present in multiple copies, unlike most protein-coding genes. The slow rate of change in rRNA genes means that multiple species sometimes share identical 16S rRNA gene sequences, while many more species share identical sequences in the short 16S rRNA regions commonly analyzed. In addition, the genes involved in many important processes are not distributed in a phylogenetically coherent manner, potentially due to gene loss or horizontal gene transfer. While rRNA genes remain the most commonly used markers, key genes in ecologically important pathways, e.g., those involved in carbon and nitrogen cycling, can provide important insights into community composition and function not obtainable through rRNA analysis. However, working with ecofunctional gene data requires some tools beyond those required for rRNA analysis. To address this, our Functional Gene Pipeline and Repository (FunGene; http://fungene.cme.msu.edu/) offers databases of many common ecofunctional genes and proteins, as well as integrated tools that allow researchers to browse these collections and choose subsets for further analysis, build phylogenetic trees, test primers and probes for coverage, and download aligned sequences. Additional FunGene tools are specialized to process coding gene amplicon data. For example, FrameBot produces frameshift-corrected protein and DNA sequences from raw reads while finding the most closely related protein reference sequence. These tools can help provide better insight into microbial communities by directly studying key genes involved in important ecological processes.

The helical ventricular myocardial band of Torrent-Guasp.

PubMed

Kocica, Mladen J; Corno, Antonio F; Lackovic, Vesna; Kanjuh, Vladimir I

2007-01-01

We live in an era of substantial progress in understanding myocardial structure and function at genetic, molecular, and microscopic levels. Yet, ventricular myocardium has proven remarkably resistant to macroscopic analyses of functional anatomy. Pronounced and practically indefinite global and local structural anisotropy of its fibers and other ventricular wall constituents produces electrical and mechanical properties that are nonlinear, anisotropic, time varying, and spatially inhomogeneous. The helical ventricular myocardial band of Torrent-Guasp is a revolutionary new concept in understanding global, 3-dimensional, functional architecture of the ventricular myocardium. This concept defines the principal, cumulative vectors, integrating the tissue architecture (ie, form) and net forces developed (ie, function) within the ventricular mass. The primary purpose of this review is to emphasize the importance of this concept, in the light of collaborative efforts to establish an integrative approach, defining ventricular form and function by linking across multiple scales of biological organization, as explained in the ongoing Physiome project. Because one of the most important scientific missions in this century is integration of basic research with clinical medicine, we believe that this knowledge is not of merely academic importance, but is also the essential prerequisite in clinical evaluation and treatment of different heart diseases.

Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

PubMed

Karimian, Ansar; Ahmadi, Yasin; Yousefi, Bahman

2016-06-01

An appropriate control over cell cycle progression depends on many factors. Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21(WAF1/Cip1)) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms. Some other important functions attributed to p21 include transcriptional regulation, modulation or inhibition of apoptosis. These functions are largely dependent on direct p21/protein interactions and also on p21 subcellular localizations. In addition, p21 can play a role in DNA repair by interacting with proliferating cell nuclear antigen (PCNA). In this review, we will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Acid-sensing ion channels: trafficking and synaptic function.

PubMed

Zha, Xiang-ming

2013-01-02

Extracellular acidification occurs in the brain with elevated neural activity, increased metabolism, and neuronal injury. This reduction in pH can have profound effects on brain function because pH regulates essentially every single biochemical reaction. Therefore, it is not surprising to see that Nature evolves a family of proteins, the acid-sensing ion channels (ASICs), to sense extracellular pH reduction. ASICs are proton-gated cation channels that are mainly expressed in the nervous system. In recent years, a growing body of literature has shown that acidosis, through activating ASICs, contributes to multiple diseases, including ischemia, multiple sclerosis, and seizures. In addition, ASICs play a key role in fear and anxiety related psychiatric disorders. Several recent reviews have summarized the importance and therapeutic potential of ASICs in neurological diseases, as well as the structure-function relationship of ASICs. However, there is little focused coverage on either the basic biology of ASICs or their contribution to neural plasticity. This review will center on these topics, with an emphasis on the synaptic role of ASICs and molecular mechanisms regulating the spatial distribution and function of these ion channels.

Building a functional multiple intelligences theory to advance educational neuroscience.

PubMed

Cerruti, Carlo

2013-01-01

A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators' complex set of questions and concerns. However, the fields of education, cognitive psychology, and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (MI; Gardner, 1983), a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a "functional MI" theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path toward constrained experimental research that bears upon teachers' concerns about teaching and learning.

Structural and functional diversity of CLAVATA3/ESR (CLE)-like genes from the potato cyst nematode Globodera rostochiensis.

PubMed

Lu, Shun-Wen; Chen, Shiyan; Wang, Jianying; Yu, Hang; Chronis, Demosthenis; Mitchum, Melissa G; Wang, Xiaohong

2009-09-01

Plant CLAVATA3/ESR-related (CLE) peptides have diverse roles in plant growth and development. Here, we report the isolation and functional characterization of five new CLE genes from the potato cyst nematode Globodera rostochiensis. Unlike typical plant CLE peptides that contain a single CLE motif, four of the five Gr-CLE genes encode CLE proteins with multiple CLE motifs. These Gr-CLE genes were found to be specifically expressed within the dorsal esophageal gland cell of nematode parasitic stages, suggesting a role for their encoded proteins in plant parasitism. Overexpression phenotypes of Gr-CLE genes in Arabidopsis mimicked those of plant CLE genes, and Gr-CLE proteins could rescue the Arabidopsis clv3-2 mutant phenotype when expressed within meristems. A short root phenotype was observed when synthetic GrCLE peptides were exogenously applied to roots of Arabidopsis or potato similar to the overexpression of Gr-CLE genes in Arabidopsis and potato hairy roots. These results reveal that G. rostochiensis CLE proteins with either single or multiple CLE motifs function similarly to plant CLE proteins and that CLE signaling components are conserved in both Arabidopsis and potato roots. Furthermore, our results provide evidence to suggest that the evolution of multiple CLE motifs may be an important mechanism for generating functional diversity in nematode CLE proteins to facilitate parasitism.

Conversion disorder: A systematic review of current terminology.

PubMed

Ding, Juen Mei; Kanaan, Richard Antony Alexander

It has been argued that the label given to unexplained neurological symptoms is an important contributor to their often poor acceptance, and there has been recent debate on proposals to change the name from conversion disorder. There have been multiple studies of layperson and clinician preference and this article aimed to review these. Multiple databases were searched using terms including "conversion disorder" and "terminology", and relative preferences for the terms extracted. Seven articles were found which looked at clinician or layperson preferences for terminology for unexplained neurological symptoms. Most neurologists favoured terms such as "functional" and "psychogenic", while laypeople were comfortable with "functional" but viewed "psychogenic" as more offensive; "non-epileptic/organic" was relatively popular with both groups. "Functional" is a term that is relatively popular with both clinicians and the public. It also meets more of the other criteria proposed for an acceptable label than other popular terms - however the views of neither psychiatrists nor actual patients with the disorder were considered. Copyright © 2016 Elsevier Inc. All rights reserved.

[Application progress of proteomic in pharmacological study of Chinese medicinal formulae].

PubMed

Liu, Yu-Qian; Zhan, Shu-Yu; Ruan, Yu-Er; Zuo, Zhi-Yan; Ji, Xiao-Ming; Wang, Shuai-Jie; Ding, Bao-Yue

2017-10-01

Chinese medicinal formulae are the important means of clinical treatment in traditional Chinese medicine. It is urgent to use modern advanced scientific and technological means to reveal the complicated mechanism of Chinese medicinal formulae because they have the function characteristics of multiple components, multiple targets and integrated regulation. The systematic and comprehensive research model of proteomic is in line with the function characteristics of Chinese medicinal formulae, and proteomic has been widely used in the study of pharmacological mechanism of Chinese medicinal formulae. The recent applications of proteomic in pharmacological study of Chinese medicinal formulae in anti-cardiovascular and cerebrovascular diseases, anti-liver disease, antidiabetic, anticancer, anti-rheumatoid arthritis and other diseases were reviewed in this paper, and then the future development direction of proteomic in pharmacological study of Chinese medicinal formulae was put forward. This review is to provide the ideas and method for proteomic research on function mechanism of Chinese medicinal formulae. Copyright© by the Chinese Pharmaceutical Association.

Cell- and virus-mediated regulation of the barrier-to-autointegration factor's phosphorylation state controls its DNA binding, dimerization, subcellular localization, and antipoxviral activity.

PubMed

Jamin, Augusta; Wicklund, April; Wiebe, Matthew S

2014-05-01

Barrier-to-autointegration factor (BAF) is a DNA binding protein with multiple cellular functions, including the ability to act as a potent defense against vaccinia virus infection. This antiviral function involves BAF's ability to condense double-stranded DNA and subsequently prevent viral DNA replication. In recent years, it has become increasingly evident that dynamic phosphorylation involving the vaccinia virus B1 kinase and cellular enzymes is likely a key regulator of multiple BAF functions; however, the precise mechanisms are poorly understood. Here we analyzed how phosphorylation impacts BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity through the characterization of BAF phosphomimetic and unphosphorylatable mutants. Our studies demonstrate that increased phosphorylation enhances BAF's mobilization from the nucleus to the cytosol, while dephosphorylation restricts BAF to the nucleus. Phosphorylation also impairs both BAF's dimerization and its DNA binding activity. Furthermore, our studies of BAF's antiviral activity revealed that hyperphosphorylated BAF is unable to suppress viral DNA replication or virus production. Interestingly, the unphosphorylatable BAF mutant, which is capable of binding DNA but localizes predominantly to the nucleus, was also incapable of suppressing viral replication. Thus, both DNA binding and localization are important determinants of BAF's antiviral function. Finally, our examination of how phosphatases are involved in regulating BAF revealed that PP2A dephosphorylates BAF during vaccinia infection, thus counterbalancing the activity of the B1 kinase. Altogether, these data demonstrate that phosphoregulation of BAF by viral and cellular enzymes modulates this protein at multiple molecular levels, thus determining its effectiveness as an antiviral factor and likely other functions as well. The barrier-to-autointegration factor (BAF) contributes to cellular genomic integrity in multiple ways, the best characterized of which are as a host defense against cytoplasmic DNA and as a regulator of mitotic nuclear reassembly. Although dynamic phosphorylation involving both viral and cellular enzymes is likely a key regulator of multiple BAF functions, the precise mechanisms involved are poorly understood. Here we demonstrate that phosphorylation coordinately regulates BAF's DNA binding, subcellular localization, dimerization, and antipoxviral activity. Overall, our findings provide new insights into how phosphoregulation of BAF modulates this protein at multiple levels and governs its effectiveness as an antiviral factor against foreign DNA.

Microbial endocrinology: Why the intersection of microbiology and neurobiology matters to poultry health.

PubMed

Villageliu, Daniel N; Lyte, Mark

2017-08-01

The union of microbiology and neurobiology has led to a revolution in the way we view the microbiome. Now recognized as important symbionts, the microorganisms which inhabit multiple niches in mammalian and avian (chicken) hosts, such as the intestinal tract and skin, serve and influence many important physiological functions. The realization that the gut microbiome serves as a kind of "microbial organ" has important implications for many areas of biology. In this paper advances in the field of microbial endocrinology which may hold relevance for the poultry industry are examined. © 2017 Poultry Science Association Inc.

Consistent role of Quaternary climate change in shaping current plant functional diversity patterns across European plant orders.

PubMed

Ordonez, Alejandro; Svenning, Jens-Christian

2017-02-23

Current and historical environmental conditions are known to determine jointly contemporary species distributions and richness patterns. However, whether historical dynamics in species distributions and richness translate to functional diversity patterns remains, for the most part, unknown. The geographic patterns of plant functional space size (richness) and packing (dispersion) for six widely distributed orders of European angiosperms were estimated using atlas distribution data and trait information. Then the relative importance of late-Quaternary glacial-interglacial climate change and contemporary environmental factors (climate, productivity, and topography) as determinants of functional diversity of evaluated orders was assesed. Functional diversity patterns of all evaluated orders exhibited prominent glacial-interglacial climate change imprints, complementing the influence of contemporary environmental conditions. The importance of Quaternary glacial-interglacial climate change factors was comparable to that of contemporary environmental factors across evaluated orders. Therefore, high long-term paleoclimate variability has imposed consistent supplementary constraints on functional diversity of multiple plant groups, a legacy that may permeate to ecosystem functioning and resilience. These findings suggest that strong near-future anthropogenic climate change may elicit long-term functional disequilibria in plant functional diversity.

The SLP-76 SH2 domain is required for T cell development and activation

PubMed Central

Burns, Jeremy C.; Corbo, Evann; Degen, Janine; Gohil, Mercy; Anterasian, Christine; Schraven, Burkart; Koretzky, Gary A.; Kliche, Stefanie; Jordan, Martha S.

2011-01-01

The adaptor protein Src homology 2 (SH2) domain containing leukocyte protein of 76 kDa (SLP-76) is critical for multiple aspects of T cell development and function. Through its protein-binding domains, SLP-76 serves as a platform for the assembly of multiple enzymes and adaptor proteins that function together to activate second messengers required for TCR signal propagation. The N-terminus of SLP-76, which contains three tyrosines that serve as docking sites for SH2 domain-containing proteins, and the central proline-rich region of SLP-76 have been well studied and are known to be important for both thymocyte selection and activation of peripheral T cells. Less is known about the function of the C-terminal SH2 domain of SLP-76. This region inducibly associates with the adhesion- and degranulation-promoting adaptor protein (ADAP) and hematopoietic progenitor kinase 1 (HPK1). Combining regulated deletion of endogenous SLP-76 with transgenic expression of a SLP-76 SH2 domain mutant, we demonstrate that the SLP-76 SH2 domain is required for peripheral T cell activation and positive selection of thymocytes, a function not previously attributed to this region. This domain is also important for T cell proliferation, IL-2 production and phosphorylation of protein kinase D (PKD) and IκB. ADAP-deficient T cells display similar, but in some cases less severe, defects despite phosphorylation of a negative regulatory site on SLP-76 by HPK1, a function that is lost in SLP-76 SH2 domain mutant T cells. PMID:21949020

Drought and increased CO2 alter floral visual and olfactory traits with context-dependent effects on pollinator visitation

Treesearch

William R. Glenny; Justin B. Runyon; Laura A. Burkle

2018-01-01

Climate change can alter species interactions essential for maintaining biodiversity and ecosystem function, such as pollination. Understanding the interactive effects of multiple abiotic conditions on floral traits and pollinator visitation are important to anticipate the implications of climate change on pollinator services. Floral visual and olfactory traits were...

Developmental Changes in Information Central to Artifact Representation: Evidence from "Functional Fluency" Tasks

ERIC Educational Resources Information Center

Defeyter, Margaret Anne; Avons, S. E.; German, Tamsin C.

2007-01-01

Research suggests that while information about design is a central feature of older children's artifact representations it may be less important in the artifact representations of younger children. Three experiments explore the pattern of responses that 5- and 7-year-old children generate when asked to produce multiple uses for familiar…

Two Sides of the Same Coin: Student-Faculty Perspectives of the Course Syllabus

ERIC Educational Resources Information Center

McDonald, Jeanette; Siddall, Gillian; Mandell, Deena; Hughes, Sandy

2010-01-01

Course syllabi play an important role in teaching, learning, and course design. They serve multiple functions and audiences and represent the end product of a scholarly process. In the following article, select findings from a mixed methods study examining how faculty and students conceptualize course syllabi are presented, specifically the design…

Developing tools for investigating the multiple roles of ethylene: Identification and mapping genes for ethylene biosynthesis and reception in barley

USDA-ARS?s Scientific Manuscript database

The plant hormone ethylene is important to many plant processes from germination through senescence, including responses to in vitro growth and plant regeneration. Knowledge of the number of genes, and of their function, that are involved in ethylene biosynthesis and reception is necessary to determ...

Pressure Points in Reading Comprehension: A Quantile Multiple Regression Analysis

ERIC Educational Resources Information Center

Logan, Jessica

2017-01-01

The goal of this study was to examine how selected pressure points or areas of vulnerability are related to individual differences in reading comprehension and whether the importance of these pressure points varies as a function of the level of children's reading comprehension. A sample of 245 third-grade children were given an assessment battery…

Correlated Longitudinal Changes across Linguistic, Achievement, and Psychomotor Domains in Early Childhood: Evidence for a Global Dimension of Development

ERIC Educational Resources Information Center

Rhemtulla, Mijke; Tucker-Drob, Elliot M.

2011-01-01

An important question within developmental psychology concerns the extent to which the maturational gains that children make across multiple diverse domains of functioning can be attributed to global (domain-general) developmental processes. The present study investigated this question by examining the extent to which individual differences in…

Managing landscapes at multiple scales for sustainability of ecosystem functions (Preface)

Treesearch

R.A. Birdsey; R. Lucas; Y. Pan; G. Sun; E.J. Gustafson; A.H.  Perera

2010-01-01

The science of landscape ecology is a rapidly evolving academic field with an emphasis on studying large-scale spatial heterogeneity created by natural influences and human activities. These advances have important implications for managing and conserving natural resources. At a September 2008 IUFRO conference in Chengdu, Sichuan, P.R. China, we highlighted both the...

A Pilot Study on Factors Involved with Work Participation in the Early Stages of Multiple Sclerosis

PubMed Central

Van der Hiele, Karin; Middelkoop, Huub A. M.; Ruimschotel, Rob; Kamminga, Noëlle G. A.; Visser, Leo H.

2014-01-01

Background Up to 30% of recently diagnosed MS patients lose their jobs in the first four years after diagnosis. Taking into account the personal and socio-economic importance of sustaining employment, it is of the utmost importance to examine factors involved with work participation. Objective To investigate differences in self-reported functioning in recently diagnosed MS patients with and without a paid job. Methods Self-reports of physical and cognitive functioning, depression, anxiety and fatigue were gathered from 44 relapsing-remitting MS patients diagnosed within 3 years. Results Patients with a paid job (57%) reported better physical functioning (p<0.001), better memory functioning (p = 0.01) and a lower physical impact of fatigue (p = 0.018) than patients without a paid job. Physical functioning was the main predictor of employment status in a logistic regression model. In those with a paid job better memory functioning (r = 0.54, p = 0.005) and a lower social impact of fatigue (r = −0.46, p = 0.029) correlated with an increased number of working hours. Conclusion Better physical functioning is the primary factor involved with increased work participation in early MS. Better self-reported memory functioning and less social fatigue were associated with increased working hours. These findings highlight the importance of battling these symptoms in the early stages of MS. PMID:25153710

Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis.

PubMed

Stillman, Chelsea M; Cohen, Jamie; Lehman, Morgan E; Erickson, Kirk I

2016-01-01

Physical activity (PA) is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

Protein function prediction--the power of multiplicity.

PubMed

Rentzsch, Robert; Orengo, Christine A

2009-04-01

Advances in experimental and computational methods have quietly ushered in a new era in protein function annotation. This 'age of multiplicity' is marked by the notion that only the use of multiple tools, multiple evidence and considering the multiple aspects of function can give us the broad picture that 21st century biology will need to link and alter micro- and macroscopic phenotypes. It might also help us to undo past mistakes by removing errors from our databases and prevent us from producing more. On the downside, multiplicity is often confusing. We therefore systematically review methods and resources for automated protein function prediction, looking at individual (biochemical) and contextual (network) functions, respectively.

The R-spondin family of proteins: emerging regulators of WNT signaling

PubMed Central

Jin, Yong-Ri; Yoon, Jeong Kyo

2012-01-01

Recently, the R-spondin (RSPO) family of proteins has emerged as important regulators of WNT signaling. Considering the wide spectrum of WNT signaling functions in normal biological processes and disease conditions, there has been a significantly growing interest in understanding the functional roles of RSPOs in multiple biological processes and determining the molecular mechanisms by which RSPOs regulate the WNT signaling pathway. Recent advances in the RSPO research field revealed some of the in vivo functions of RSPOs and provided new information regarding the mechanistic roles of RSPO activity in regulation of WNT signaling. Herein, we review recent progress in RSPO research with an emphasis on signaling mechanisms and biological functions. PMID:22982762

Determinants of the rate of protein sequence evolution

PubMed Central

Zhang, Jianzhi; Yang, Jian-Rong

2015-01-01

The rate and mechanism of protein sequence evolution have been central questions in evolutionary biology since the 1960s. Although the rate of protein sequence evolution depends primarily on the level of functional constraint, exactly what constitutes functional constraint has remained unclear. The increasing availability of genomic data has allowed for much needed empirical examinations on the nature of functional constraint. These studies found that the evolutionary rate of a protein is predominantly influenced by its expression level rather than functional importance. A combination of theoretical and empirical analyses have identified multiple mechanisms behind these observations and demonstrated a prominent role that selection against errors in molecular and cellular processes plays in protein evolution. PMID:26055156

Echocardiographic assessment of left ventricular diastolic function.

PubMed

Pirat, Bahar; Zoghbi, William A

2007-09-01

Assessment of diastolic function and left ventricular filling pressures in the setting of both normal and reduced systolic function is of major importance particularly in patients with dyspnea. Since multiple echocardiography parameters are used to assess diastolic function each with some limitations, a comprehensive approach should be applied. Transmitral Doppler flow should be evaluated in combination with newer, less load dependent Doppler techniques. Tissue Doppler imaging provides accurate, well validated data regarding diastolic properties and filling pressures of the left ventricle. Tissue Doppler imaging should be the part of a routine echocardiography study due to its ease of use and high reproducibility. Pulmonary vein Doppler and flow propagation velocity should be incorporated into the evaluation when needed.

The importance of hippocampal dynamic connectivity in explaining memory function in multiple sclerosis.

PubMed

van Geest, Quinten; Hulst, Hanneke E; Meijer, Kim A; Hoyng, Lieke; Geurts, Jeroen J G; Douw, Linda

2018-05-01

Brain dynamics (i.e., variable strength of communication between areas), even at the scale of seconds, are thought to underlie complex human behavior, such as learning and memory. In multiple sclerosis (MS), memory problems occur often and have so far only been related to "stationary" brain measures (e.g., atrophy, lesions, activation and stationary (s) functional connectivity (FC) over an entire functional scanning session). However, dynamics in FC (dFC) between the hippocampus and the (neo)cortex may be another important neurobiological substrate of memory impairment in MS that has not yet been explored. Therefore, we investigated hippocampal dFC during a functional (f) magnetic resonance imaging (MRI) episodic memory task and its relationship with verbal and visuospatial memory performance outside the MR scanner. Thirty-eight MS patients and 29 healthy controls underwent neuropsychological tests to assess memory function. Imaging (1.5T) was obtained during performance of a memory task. We assessed hippocampal volume, functional activation, and sFC (i.e., FC of the hippocampus with the rest of the brain averaged over the entire scan, using an atlas-based approach). Dynamic FC of the hippocampus was calculated using a sliding window approach. No group differences were found in hippocampal activation, sFC, and dFC. However, stepwise forward regression analyses in patients revealed that lower dFC of the left hippocampus (standardized β = -0.30; p  =   .021) could explain an additional 7% of variance (53% in total) in verbal memory, in addition to female sex and larger left hippocampal volume. For visuospatial memory, lower dFC of the right hippocampus (standardized β = -0.38; p  =   .013) could explain an additional 13% of variance (24% in total) in addition to higher sFC of the right hippocampus. Low hippocampal dFC is an important indicator for maintained memory performance in MS, in addition to other hippocampal imaging measures. Hence, brain dynamics may offer new insights into the neurobiological mechanisms underlying memory (dys)function.

BLNK: molecular scaffolding through ‘cis’-mediated organization of signaling proteins

PubMed Central

Chiu, Christopher W.; Dalton, Mark; Ishiai, Masamichi; Kurosaki, Tomohiro; Chan, Andrew C.

2002-01-01

Assembly of intracellular macromolecular complexes is thought to provide an important mechanism to coordinate the generation of second messengers upon receptor activation. We have previously identified a B cell linker protein, termed BLNK, which serves such a scaffolding function in B cells. We demonstrate here that phosphorylation of five tyrosine residues within human BLNK nucleates distinct signaling effectors following B cell antigen receptor activation. The phosphorylation of multiple tyrosine residues not only amplifies PLCγ-mediated signaling but also supports ‘cis’-mediated interaction between distinct signaling effectors within a large molecular complex. These data demonstrate the importance of coordinate phosphorylation of molecular scaffolds, and provide insights into how assembly of macromolecular complexes is required for normal receptor function. PMID:12456653

PROBING HUMAN AND MONKEY ANTERIOR CINGULATE CORTEX IN VARIABLE ENVIRONMENTS

PubMed Central

Walton, Mark E.; Mars, Rogier B.

2008-01-01

Previous research has identified the anterior cingulate cortex (ACC) as an important node in the neural network underlying decision making in primates. Decision making can, however, be studied under large variety of circumstances, ranging from the standard well-controlled lab situation to more natural, stochastic settings during which multiple agents interact. Here, we illustrate how these different varieties of decision making studied can influence theories of ACC function in monkeys. Converging evidence from unit recordings and lesions studies now suggest that the ACC is important for interpreting outcome information according to the current task context to guide future action selection. We then apply this framework to the study of human ACC function and discuss its potential implications. PMID:18189014

The messenger matters: Pollinator functional group influences mating system dynamics.

PubMed

Weber, Jennifer J

2017-08-01

The incredible diversity of plant mating systems has fuelled research in evolutionary biology for over a century. Currently, there is broad concern about the impact of rapidly changing pollinator communities on plant populations. Very few studies, however, examine patterns and mechanisms associated with multiple paternity from cross-pollen loads. Often, foraging pollinators collect a mixed pollen load that may result in the deposition of pollen from different sires to receptive stigmas. Coincident deposition of self- and cross-pollen leads to interesting mating system dynamics and has been investigated in numerous species. But, mixed pollen loads often consist of a diversity of cross-pollen and result in multiple sires of seeds within a fruit. In this issue of Molecular Ecology, Rhodes, Fant, and Skogen () examine how pollinator identity and spatial isolation influence multiple paternity within fruits of a self-incompatible evening primrose. The authors demonstrate that pollen pool diversity varies between two pollinator types, hawkmoths and diurnal solitary bees. Further, progeny from more isolated plants were less likely to have multiple sires regardless of the pollinator type. Moving forward, studies of mating system dynamics should consider the implications of multiple paternity and move beyond the self- and cross-pollination paradigm. Rhodes et al. () demonstrate the importance of understanding the roles that functionally diverse pollinators play in mating system dynamics. © 2017 John Wiley & Sons Ltd.

Novel TDP2-ubiquitin interactions and their importance for the repair of topoisomerase II-mediated DNA damage

PubMed Central

Rao, Timsi; Gao, Rui; Takada, Saeko; Al Abo, Muthana; Chen, Xiang; Walters, Kylie J.; Pommier, Yves; Aihara, Hideki

2016-01-01

Tyrosyl DNA phosphodiesterase 2 (TDP2) is a multifunctional protein implicated in DNA repair, signal transduction and transcriptional regulation. In its DNA repair role, TDP2 safeguards genome integrity by hydrolyzing 5′-tyrosyl DNA adducts formed by abortive topoisomerase II (Top2) cleavage complexes to allow error-free repair of DNA double-strand breaks, thereby conferring cellular resistance against Top2 poisons. TDP2 consists of a C-terminal catalytic domain responsible for its phosphodiesterase activity, and a functionally uncharacterized N-terminal region. Here, we demonstrate that this N-terminal region contains a ubiquitin (Ub)-associated (UBA) domain capable of binding multiple forms of Ub with distinct modes of interactions and preference for either K48- or K63-linked polyUbs over monoUb. The structure of TDP2 UBA bound to monoUb shows a canonical mode of UBA-Ub interaction. However, the absence of the highly conserved MGF motif and the presence of a fourth α-helix make TDP2 UBA distinct from other known UBAs. Mutations in the TDP2 UBA-Ub binding interface do not affect nuclear import of TDP2, but severely compromise its ability to repair Top2-mediated DNA damage, thus establishing the importance of the TDP2 UBA–Ub interaction in DNA repair. The differential binding to multiple Ub forms could be important for responding to DNA damage signals under different contexts or to support the multi-functionality of TDP2. PMID:27543075

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.

PubMed

Feinstein, Anthony; Freeman, Jenny; Lo, Albert C

2015-02-01

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

A passive exoskeleton can push your life up: application on multiple sclerosis patients.

PubMed

Di Russo, Francesco; Berchicci, Marika; Perri, Rinaldo Livio; Ripani, Francesca Romana; Ripani, Maurizio

2013-01-01

In the present study, we report the benefits of a passive and fully articulated exoskeleton on multiple sclerosis patients by means of behavioral and electrophysiological measures, paying particular attention to the prefrontal cortex activity. Multiple sclerosis is a neurological condition characterized by lesions of the myelin sheaths that encapsulate the neurons of the brain, spine and optic nerve, and it causes transient or progressive symptoms and impairments in gait and posture. Up to 50% of multiple sclerosis patients require walking aids and 10% are wheelchair-bound 15 years following the initial diagnosis. We tested the ability of a new orthosis, the "Human Body Posturizer", designed to improve the structural and functional symmetry of the body through proprioception, in multiple sclerosis patients. We observed that a single Human Body Posturizer application improved mobility, ambulation and response accuracy, in all of the tested patients. Most importantly, we associated these clinical observations and behavioral effects to changes in brain activity, particularly in the prefrontal cortex.

Melatonin transport into mitochondria.

PubMed

Mayo, Juan C; Sainz, Rosa M; González-Menéndez, Pedro; Hevia, David; Cernuda-Cernuda, Rafael

2017-11-01

Melatonin is a well-known, nighttime-produced indole found in bacteria, eukaryotic unicellulars, animals or vascular plants. In vertebrates, melatonin is the major product of the pineal gland, which accounts for its increase in serum during the dark phase, but it is also produced by many other organs and cell types. Such a wide distribution is consistent with its multiple and well-described functions which include from the circadian regulation and adaptation to seasonal variations to immunomodulatory and oncostatic actions in different types of tumors. The discovery of its antioxidant properties in the early 1990s opened a new field of potential protective functions in multiple tissues. A special mention should be made regarding the nervous system, where the indole is considered a major neuroprotector. Furthermore, mitochondria appear as one of the most important targets for the indole's protective actions. Melatonin's mechanisms of action vary from the direct molecular interaction with free radicals (free radical scavenger) to the binding to membrane (MLT1A and MLT1B) or nuclear receptors (RZR/RORα). Receptor binding has been associated with some, but not all of the indole functions reported to date. Recently, two new mechanisms of cellular uptake involving the facilitative glucose transporters GLUT/SLC2A and the proton-driven oligopeptide transporter PEPT1/2 have been reported. Here we discuss the potential importance that these newly discovered transport systems could have in determining the actions of melatonin, particularly in the mitochondria. We also argue the relative importance of passive diffusion vs active transport in different parts of the cell.

What have we learned about GPER function in physiology and disease from knockout mice?

PubMed

Prossnitz, Eric R; Hathaway, Helen J

2015-09-01

Estrogens, predominantly 17β-estradiol, exert diverse effects throughout the body in both normal and pathophysiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ERα and ERβ) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ERα KO mice display multiple significant defects in reproduction and mammary gland development, ERβ KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also demonstrated roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer. Copyright © 2015. Published by Elsevier Ltd.

Walking impairment in patients with multiple sclerosis: exercise training as a treatment option.

PubMed

Motl, Robert W; Goldman, Myla D; Benedict, Ralph H B

2010-11-16

Multiple sclerosis (MS) is a chronic disease of the central nervous system that culminates in the progression of physical and cognitive disability over time. Walking impairment is a ubiquitous feature of MS and a sentinel characteristic of the later or advanced stages of the disease. This paper presents a conceptual rationale along with empirical evidence for exercise training as a rehabilitation approach for managing walking impairment and improving walking function in persons with MS. Conceptually, MS is associated with a decrease in physical activity, which, in turn, can result in deconditioning across multiple domains of physiological functioning. The resulting deconditioning feeds back and further drives physical inactivity until a threshold is reached that likely initiates the progression of walking impairment in MS. Empirically, physical activity and exercise training have been associated with beneficial effects on walking function in persons with MS. This is based on cross-sectional, longitudinal, and experimental research that included diversity in the breadth of measures of walking, persons with MS, and exercise/physical activity characteristics. Of particular importance, future researchers might consider examining the combinatory effects of exercise training plus pharmacological agents on walking mobility in MS. Collectively, exercise training and physical activity might hold significant potential for the management of progressive mobility disability in MS.

Vps15 is required for stress induced and developmentally triggered autophagy and salivary gland protein secretion in Drosophila.

PubMed

Anding, A L; Baehrecke, E H

2015-03-01

Autophagy is a catabolic process used to deliver cellular material to the lysosome for degradation. The core Vps34/class III phosphatidylinositol 3-kinase (PI3K) complex, consisting of Atg6, Vps15, and Vps34, is highly conserved throughout evolution, critical for recruiting autophagy-related proteins to the preautophagosomal structure and for other vesicular trafficking processes, including vacuolar protein sorting. Atg6 and Vps34 have been well characterized, but the Vps15 kinase remains poorly characterized with most studies focusing on nutrient deprivation-induced autophagy. Here, we investigate the function of Vps15 in different cellular contexts and find that it is necessary for both stress-induced and developmentally programmed autophagy in various tissues in Drosophila melanogaster. Vps15 is required for autophagy that is induced by multiple forms of stress, including nutrient deprivation, hypoxia, and oxidative stress. Furthermore, autophagy that is triggered by physiological stimuli during development in the fat body, intestine, and salivary gland also require the function of Vps15. In addition, we show that Vps15 is necessary for efficient salivary gland protein secretion. These data illustrate the broad importance of Vps15 in multiple forms of autophagy in different animal cells, and also highlight the pleiotropic function of this kinase in multiple vesicle-trafficking pathways.

Soil properties, soil functions and soil security

NASA Astrophysics Data System (ADS)

Poggio, Laura; Gimona, Alessandro

2017-04-01

Soil plays a crucial role in the ecosystem functioning such as food production, capture and storage of water, carbon and nutrients and in the realisation of a number of UN Sustainable Developments Goals. In this work we present an approach to spatially and jointly assess the multiple contributions of soil to the delivery of ecosystem services within multiple land-use system. We focussed on the modelling of the impact of soil on sediment retention, carbon storage, storing and filtering of nutrients, habitat for soil organisms and water regulation, taking into account examples of land use and climate scenarios. Simplified models were used for the single components. Spatialised Bayesian Belief networks were used for the jointly assessment and mapping of soil contribution to multiple land use and ecosystem services. We integrated continuous 3D soil information derived from digital soil mapping approaches covering the whole of mainland Scotland, excluding the Northern Islands. Uncertainty was accounted for and propagated across the whole process. The Scottish test case highlights the differences in roles between mineral and organic soils and provides an example of integrated study assessing the contributions of soil. The results show the importance of the multi-functional analysis of the contribution of soils to the ecosystem service delivery and UN SDGs.

Comprehensive Method for Culturing Embryonic Dorsal Root Ganglion Neurons for Seahorse Extracellular Flux XF24 Analysis

PubMed Central

Lange, Miranda; Zeng, Yan; Knight, Andrew; Windebank, Anthony; Trushina, Eugenia

2012-01-01

Changes in mitochondrial dynamics and function contribute to progression of multiple neurodegenerative diseases including peripheral neuropathies. The Seahorse Extracellular Flux XF24 analyzer provides a comprehensive assessment of the relative state of glycolytic and aerobic metabolism in live cells making this method instrumental in assessing mitochondrial function. One of the most important steps in the analysis of mitochondrial respiration using the Seahorse XF24 analyzer is plating a uniform monolayer of firmly attached cells. However, culturing of primary dorsal root ganglion (DRG) neurons is associated with multiple challenges, including their propensity to form clumps and detach from the culture plate. This could significantly interfere with proper analysis and interpretation of data. We have tested multiple cell culture parameters including coating substrates, culture medium, XF24 microplate plastics, and plating techniques in order to optimize plating conditions. Here we describe a highly reproducible method to obtain neuron-enriched monolayers of securely attached dissociated primary embryonic (E15) rat DRG neurons suitable for analysis with the Seahorse XF24 platform. PMID:23248613

Multiple-wavelength neutron holography with pulsed neutrons

PubMed Central

Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

2017-01-01

Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering—that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique. PMID:28835917

Comprehensive Method for Culturing Embryonic Dorsal Root Ganglion Neurons for Seahorse Extracellular Flux XF24 Analysis.

PubMed

Lange, Miranda; Zeng, Yan; Knight, Andrew; Windebank, Anthony; Trushina, Eugenia

2012-01-01

Changes in mitochondrial dynamics and function contribute to progression of multiple neurodegenerative diseases including peripheral neuropathies. The Seahorse Extracellular Flux XF24 analyzer provides a comprehensive assessment of the relative state of glycolytic and aerobic metabolism in live cells making this method instrumental in assessing mitochondrial function. One of the most important steps in the analysis of mitochondrial respiration using the Seahorse XF24 analyzer is plating a uniform monolayer of firmly attached cells. However, culturing of primary dorsal root ganglion (DRG) neurons is associated with multiple challenges, including their propensity to form clumps and detach from the culture plate. This could significantly interfere with proper analysis and interpretation of data. We have tested multiple cell culture parameters including coating substrates, culture medium, XF24 microplate plastics, and plating techniques in order to optimize plating conditions. Here we describe a highly reproducible method to obtain neuron-enriched monolayers of securely attached dissociated primary embryonic (E15) rat DRG neurons suitable for analysis with the Seahorse XF24 platform.

Multiple-wavelength neutron holography with pulsed neutrons.

PubMed

Hayashi, Kouichi; Ohoyama, Kenji; Happo, Naohisa; Matsushita, Tomohiro; Hosokawa, Shinya; Harada, Masahide; Inamura, Yasuhiro; Nitani, Hiroaki; Shishido, Toetsu; Yubuta, Kunio

2017-08-01

Local structures around impurities in solids provide important information for understanding the mechanisms of material functions, because most of them are controlled by dopants. For this purpose, the x-ray absorption fine structure method, which provides radial distribution functions around specific elements, is most widely used. However, a similar method using neutron techniques has not yet been developed. If one can establish a method of local structural analysis with neutrons, then a new frontier of materials science can be explored owing to the specific nature of neutron scattering-that is, its high sensitivity to light elements and magnetic moments. Multiple-wavelength neutron holography using the time-of-flight technique with pulsed neutrons has great potential to realize this. We demonstrated multiple-wavelength neutron holography using a Eu-doped CaF 2 single crystal and obtained a clear three-dimensional atomic image around trivalent Eu substituted for divalent Ca, revealing an interesting feature of the local structure that allows it to maintain charge neutrality. The new holography technique is expected to provide new information on local structures using the neutron technique.

Methodology to develop crash modification functions for road safety treatments with fully specified and hierarchical models.

PubMed

Chen, Yongsheng; Persaud, Bhagwant

2014-09-01

Crash modification factors (CMFs) for road safety treatments are developed as multiplicative factors that are used to reflect the expected changes in safety performance associated with changes in highway design and/or the traffic control features. However, current CMFs have methodological drawbacks. For example, variability with application circumstance is not well understood, and, as important, correlation is not addressed when several CMFs are applied multiplicatively. These issues can be addressed by developing safety performance functions (SPFs) with components of crash modification functions (CM-Functions), an approach that includes all CMF related variables, along with others, while capturing quantitative and other effects of factors and accounting for cross-factor correlations. CM-Functions can capture the safety impact of factors through a continuous and quantitative approach, avoiding the problematic categorical analysis that is often used to capture CMF variability. There are two formulations to develop such SPFs with CM-Function components - fully specified models and hierarchical models. Based on sample datasets from two Canadian cities, both approaches are investigated in this paper. While both model formulations yielded promising results and reasonable CM-Functions, the hierarchical model was found to be more suitable in retaining homogeneity of first-level SPFs, while addressing CM-Functions in sub-level modeling. In addition, hierarchical models better capture the correlations between different impact factors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional group diversity is key to Southern Ocean benthic carbon pathways

PubMed Central

Sands, Chester J.

2017-01-01

High latitude benthos are globally important in terms of accumulation and storage of ocean carbon, and the feedback this is likely to have on regional warming. Understanding this ecosystem service is important but difficult because of complex taxonomic diversity, history and geography of benthic biomass. Using South Georgia as a model location (where the history and geography of benthic biology is relatively well studied) we investigated whether the composition of functional groups were critical to benthic accumulation, immobilization and burial pathway to sequestration–and also aid their study through simplification of identification. We reclassified [1], [2]) morphotype and carbon mass data to 13 functional groups, for each sample of 32 sites around the South Georgia continental shelf. We investigated the influence on carbon accumulation, immobilization and sequestration estimate by multiple factors including the compositions of functional groups. Functional groups showed high diversity within and between sites, and within and between habitat types. Carbon storage was not linked to a functional group in particular but accumulation and immobilization increased with the number of functional groups present and the presence of hard substrata. Functional groups were also important to carbon burial rate, which increased with the presence of mixed (hard and soft substrata). Functional groups showed high surrogacy for taxonomic composition and were useful for examining contrasting habitat categorization. Functional groups not only aid marine carbon storage investigation by reducing time and the need for team size and speciality, but also important to benthic carbon pathways per se. There is a distinct geography to seabed carbon storage; seabed boulder-fields are hotspots of carbon accumulation and immobilization, whilst the interface between such boulder-fields and sediments are key places for burial and sequestration. PMID:28654664

Physical activity, self-efficacy, and health-related quality of life in persons with multiple sclerosis: analysis of associations between individual-level changes over one year.

PubMed

Motl, Robert W; McAuley, Edward; Wynn, Daniel; Sandroff, Brian; Suh, Yoojin

2013-03-01

Physical activity and self-efficacy represent behavioral and psychological factors, respectively, that are compromised in persons with multiple sclerosis (MS), but might be modifiable through intervention and result in better health-related quality of life (HRQOL). The present study adopted a panel research design and examined the associations between individual-level changes in physical activity, self-efficacy, and HRQOL over a one-year period in persons with MS. The sample consisted of 269 persons with relapsing-remitting MS who completed the Godin Leisure-Time Questionnaire (GLTEQ), Multiple Sclerosis Self-Efficacy (MSSE) Scale, and Multiple Sclerosis Quality of Life-29 (MSIS-29) Scale on two occasions that were separated by 1 year. The data were analyzed using panel analysis in Mplus 3.0. The initial panel analysis indicated that individual-level change in physical activity was associated with individual-level change in both physical and psychological HRQOL. The subsequent panel analysis indicated that (a) individual-level change in self-efficacy for functioning with MS was associated with individual-level change in physical HRQOL, whereas individual-level change in self-efficacy for control was associated with individual-level change in psychological HRQOL; (b) individual-level change in self-efficacy for functioning with MS, but not self-efficacy for control, mediated the association between individual-level change in physical activity and physical HRQOL; and (c) individual-level change in self-efficacy for controlling MS was the strongest predictor of individual-level change in HRQOL. Physical activity and self-efficacy both might be important targets of subsequent behavioral and self-management interventions for improving the HRQOL of persons with MS, although self-efficacy is seemingly more important than physical activity.

Functional traits help to explain half-century long shifts in pollinator distributions.

PubMed

Aguirre-Gutiérrez, Jesús; Kissling, W Daniel; Carvalheiro, Luísa G; WallisDeVries, Michiel F; Franzén, Markus; Biesmeijer, Jacobus C

2016-04-15

Changes in climate and land use can have important impacts on biodiversity. Species respond to such environmental modifications by adapting to new conditions or by shifting their geographic distributions towards more suitable areas. The latter might be constrained by species' functional traits that influence their ability to move, reproduce or establish. Here, we show that functional traits related to dispersal, reproduction, habitat use and diet have influenced how three pollinator groups (bees, butterflies and hoverflies) responded to changes in climate and land-use in the Netherlands since 1950. Across the three pollinator groups, we found pronounced areal range expansions (>53%) and modelled range shifts towards the north (all taxa: 17-22 km), west (bees: 14 km) and east (butterflies: 11 km). The importance of specific functional traits for explaining distributional changes varied among pollinator groups. Larval diet preferences (i.e. carnivorous vs. herbivorous/detritivorous and nitrogen values of host plants, respectively) were important for hoverflies and butterflies, adult body size for hoverflies, and flight period length for all groups. Moreover, interactions among multiple traits were important to explain species' geographic range shifts, suggesting that taxon-specific multi-trait analyses are needed to predict how global change will affect biodiversity and ecosystem services.

Ionic self-assembly for functional hierarchical nanostructured materials.

PubMed

Faul, Charl F J

2014-12-16

CONSPECTUS: The challenge of constructing soft functional materials over multiple length scales can be addressed by a number of different routes based on the principles of self-assembly, with the judicious use of various noncovalent interactions providing the tools to control such self-assembly processes. It is within the context of this challenge that we have extensively explored the use of an important approach for materials construction over the past decade: exploiting electrostatic interactions in our ionic self-assembly (ISA) method. In this approach, cooperative assembly of carefully chosen charged surfactants and oppositely charged building blocks (or tectons) provides a facile noncovalent route for the rational design and production of functional nanostructured materials. Generally, our research efforts have developed with an initial focus on establishing rules for the construction of novel noncovalent liquid-crystalline (LC) materials. We found that the use of double-tailed surfactant species (especially branched double-tailed surfactants) led to the facile formation of thermotropic (and, in certain cases, lyotropic) phases, as demonstrated by extensive temperature-dependent X-ray and light microscopy investigations. From this core area of activity, research expanded to cover issues beyond simple construction of anisotropic materials, turning to the challenge of inclusion and exploitation of switchable functionality. The use of photoactive azobenzene-containing ISA materials afforded opportunities to exploit both photo-orientation and surface relief grating formation. The preparation of these anisotropic LC materials was of interest, as the aim was the facile production of disposable and low-cost optical components for display applications and data storage. However, the prohibitive cost of the photo-orientation processes hampered further exploitation of these materials. We also expanded our activities to explore ISA of biologically relevant tectons, specifically deoxyguanosine monophosphate. This approach proved, in combination with block copolymer (BCP) self-assembly, very fruitful for the construction of complex and hierarchical functional materials across multiple length scales. Molecular frustration and incommensurability, which played a major role in structure formation in combination with nucleotide assembly, have now become important tools to tune supramolecular structure formation. These concepts, that is, the use of BCP assembly and incommensurability, in combination with metal-containing polymeric materials, have provided access to novel supramolecular morphologies and, more importantly, design rules to prepare such constructs. These design rules are now also being applied to the assembly of electroactive oligo(aniline)-based materials for the preparation of highly ordered functional soft materials, and present an opportunity for materials development for applications in energy storage. In this Account, we therefore discuss investigations into (i) the inclusion and preparation of supramolecular photoactive and electroactive materials; (ii) the exploitation and control over multiple noncovalent interactions to fine-tune function, internal structure, and long-range order and (iii) exploration of construction over multiple length scales by combination of ISA with well-known BCP self-assembly. Combination of ISA with tuning of volume fractions, mutual compatibility, and molecular frustration now provides a versatile tool kit to construct complex and hierarchical functional materials in a facile noncovalent way. A direct challenge for future ISA activities would certainly be the construction of functional mesoscale objects. However, within a broader scientific context, the challenge would be to exploit this powerful assembly tool for application in areas of research with societal impact, for example, energy storage and generation. The hope is that this Account will provide a platform for such future research activities and opportunities.

Functional and mechanistic diversity of distal transcription enhancers

PubMed Central

Bulger, Michael; Groudine, Mark

2013-01-01

Biological differences among metazoans, and between cell types in a given organism, arise in large part due to differences in gene expression patterns. The sequencing of multiple metazoan genomes, coupled with recent advances in genome-wide analysis of histone modifications and transcription factor binding, has revealed that among regulatory DNA sequences, gene-distal enhancers appear to exhibit the greatest diversity and cell-type specificity. Moreover, such elements are emerging as important targets for mutations that can give rise to disease and to genetic variability that underlies evolutionary change. Studies of long-range interactions between distal genomic sequences in the nucleus indicate that enhancers are often important determinants of nuclear organization, contributing to a general model for enhancer function that involves direct enhancer-promoter contact. In a number of systems, however, mechanisms for enhancer function are emerging that do not fit solely within such a model, suggesting that enhancers as a class of DNA regulatory element may be functionally and mechanistically diverse. PMID:21295696

Biodegradable polymeric microsphere-based vaccines and their applications in infectious diseases

PubMed Central

Lin, Chi-Ying; Lin, Shih-Jie; Yang, Yi-Chen; Wang, Der-Yuan; Cheng, Hwei-Fang; Yeh, Ming-Kung

2015-01-01

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits. PMID:25839217

p21/Cyclin E pathway modulates anticlastogenic function of Bmi-1 in cancer cells

PubMed Central

Deng, Wen; Zhou, Yuan; Tiwari, Agnes FY; Su, Hang; Yang, Jie; Zhu, Dandan; Lau, Victoria Ming Yi; Hau, Pok Man; Yip, Yim Ling; Cheung, Annie LM; Guan, Xin-Yuan; Tsao, Sai Wah

2015-01-01

Apart from regulating stem cell self-renewal, embryonic development and proliferation, Bmi-1 has been recently reported to be critical in the maintenance of genome integrity. In searching for novel mechanisms underlying the anticlastogenic function of Bmi-1, we observed, for the first time, that Bmi-1 positively regulates p21 expression. We extended the finding that Bmi-1 deficiency induced chromosome breaks in multiple cancer cell models. Interestingly, we further demonstrated that knockdown of cyclin E or ectopic overexpression of p21 rescued Bmi-1 deficiency-induced chromosome breaks. We therefore conclude that p21/cyclin E pathway is crucial in modulating the anticlastogenic function of Bmi-1. As it is well established that the overexpression of cyclin E potently induces genome instability and p21 suppresses the function of cyclin E, the novel and important implication from our findings is that Bmi-1 plays an important role in limiting genomic instability in cylin E-overexpressing cancer cells by positive regulation of p21. PMID:25131797

The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability.

PubMed

Myers, Katie N; Barone, Giancarlo; Ganesh, Anil; Staples, Christopher J; Howard, Anna E; Beveridge, Ryan D; Maslen, Sarah; Skehel, J Mark; Collis, Spencer J

2016-10-14

It was recently discovered that vertebrate genomes contain multiple endogenised nucleotide sequences derived from the non-retroviral RNA bornavirus. Strikingly, some of these elements have been evolutionary maintained as open reading frames in host genomes for over 40 million years, suggesting that some endogenised bornavirus-derived elements (EBL) might encode functional proteins. EBLN1 is one such element established through endogenisation of the bornavirus N gene (BDV N). Here, we functionally characterise human EBLN1 as a novel regulator of genome stability. Cells depleted of human EBLN1 accumulate DNA damage both under non-stressed conditions and following exogenously induced DNA damage. EBLN1-depleted cells also exhibit cell cycle abnormalities and defects in microtubule organisation as well as premature centrosome splitting, which we attribute in part, to improper localisation of the nuclear envelope protein TPR. Our data therefore reveal that human EBLN1 possesses important cellular functions within human cells, and suggest that other EBLs present within vertebrate genomes may also possess important cellular functions.

Acetylation of pregnane X receptor protein determines selective function independent of ligand activation

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

Biswas, Arunima; Pasquel, Danielle; Tyagi, Rakesh Kumar

2011-03-18

Research highlights: {yields} Pregnane X receptor (PXR), a major regulatory protein, is modified by acetylation. {yields} PXR undergoes dynamic deacetylation upon ligand-mediated activation. {yields} SIRT1 partially mediates PXR deacetylation. {yields} PXR deacetylation per se induces lipogenesis mimicking ligand-mediated activation. -- Abstract: Pregnane X receptor (PXR), like other members of its class of nuclear receptors, undergoes post-translational modification [PTM] (e.g., phosphorylation). However, it is unknown if acetylation (a major and common form of protein PTM) is observed on PXR and, if it is, whether it is of functional consequence. PXR has recently emerged as an important regulatory protein with multiple ligand-dependentmore » functions. In the present work we show that PXR is indeed acetylated in vivo. SIRT1 (Sirtuin 1), a NAD-dependent class III histone deacetylase and a member of the sirtuin family of proteins, partially mediates deacetylation of PXR. Most importantly, the acetylation status of PXR regulates its selective function independent of ligand activation.« less

Visual function affects prosocial behaviors in older adults.

PubMed

Teoli, Dac A; Smith, Merideth D; Leys, Monique J; Jain, Priyanka; Odom, J Vernon

2016-02-01

Eye-related pathological conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration commonly lead to decreased peripheral/central field, decreased visual acuity, and increased functional disability. We sought to answer if relationships exist between measures of visual function and reported prosocial behaviors in an older adult population with eye-related diagnoses. The sample consisted of adults, aged ≥ 60 years old, at an academic hospital's eye institute. Vision ranged from normal to severe impairment. Medical charts determined the visual acuities, ocular disease, duration of disease (DD), and visual fields (VF). Measures of giving help were via validated questionnaires on giving formal support (GFS) and giving informal support; measures of help received were perceived support (PS) and informal support received (ISR). ISR had subscales: tangible support (ISR-T), emotional support (ISR-E), and composite (ISR-C). Visual acuities of the better and worse seeing eyes were converted to LogMAR values. VF information converted to a 4-point rating scale of binocular field loss severity. DD was in years. Among 96 participants (mean age 73.28; range 60-94), stepwise regression indicated a relationship of visual variables to GFS (p < 0.05; Multiple R (2) = 0.1679 with acuity-better eye, VF rating, and DD), PS (p < 0.05; Multiple R (2) = 0.2254 with acuity-better eye), ISR-C (p < 0.05; Multiple R (2) = 0.041 with acuity-better eye), and ISR-T (p < 0.05; Multiple R (2) = 0.1421 with acuity-better eye). The findings suggest eye-related conditions can impact levels and perceptions of support exchanges. Our data reinforces the importance of visual function as an influence on prosocial behavior in older adults.

Advanced statistics: linear regression, part II: multiple linear regression.

PubMed

Marill, Keith A

2004-01-01

The applications of simple linear regression in medical research are limited, because in most situations, there are multiple relevant predictor variables. Univariate statistical techniques such as simple linear regression use a single predictor variable, and they often may be mathematically correct but clinically misleading. Multiple linear regression is a mathematical technique used to model the relationship between multiple independent predictor variables and a single dependent outcome variable. It is used in medical research to model observational data, as well as in diagnostic and therapeutic studies in which the outcome is dependent on more than one factor. Although the technique generally is limited to data that can be expressed with a linear function, it benefits from a well-developed mathematical framework that yields unique solutions and exact confidence intervals for regression coefficients. Building on Part I of this series, this article acquaints the reader with some of the important concepts in multiple regression analysis. These include multicollinearity, interaction effects, and an expansion of the discussion of inference testing, leverage, and variable transformations to multivariate models. Examples from the first article in this series are expanded on using a primarily graphic, rather than mathematical, approach. The importance of the relationships among the predictor variables and the dependence of the multivariate model coefficients on the choice of these variables are stressed. Finally, concepts in regression model building are discussed.

Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms.

PubMed Central

Zhao, Xiangshan; Gan, Lixia; Pan, Haiyun; Kan, Donghui; Majeski, Michael; Adam, Stephen A; Unterman, Terry G

2004-01-01

FOXO1, a Forkhead transcription factor, is an important target of insulin and growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS (nuclear localization signal) in the C-terminal basic region of the DBD (DNA-binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export signal) located further downstream. Here, we find that other elements in the DBD also contribute to nuclear localization, and that multiple mechanisms contribute to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1-149) also is sufficient to promote nuclear exclusion, and does so through multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24 is required for this effect. A leucine-rich, leptomycin B-sensitive export signal is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co-precipitation studies with tagged proteins indicate that 14-3-3 binding involves co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA-binding and with nuclear-localization functions. Together, these studies demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular distribution and function of FOXO1 through multiple mechanisms. The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. PMID:14664696

Identification of Ind transcription activation and repression domains required for dorsoventral patterning of the CNS.

PubMed

Von Ohlen, Tonia L; Moses, Cade

2009-07-01

Specification of cell fates across the dorsoventral axis of the central nervous system in Drosophila involves the subdivision of the neuroectoderm into three domains that give rise to three columns of neural precursor cells called neuroblasts. Ventral nervous system defective (Vnd), intermediate neuroblasts defective (Ind) and muscle segment homeobox (Msh) are expressed in the three columns from ventral to dorsal, respectively. The products of these genes play multiple important roles in formation and specification of the embryonic nervous system. Ind, for example, is known to play roles in two important processes. First, Ind is essential for formation of neuroblasts conjunction with SoxB class transcription factors. Sox class transcription factors are known to specify neural stem cells in vertebrates. Second, Ind plays an important role in patterning the CNS in conjunction with, vnd and msh, which is also similar to how vertebrates pattern their neural tube. This work focuses two important aspects of Ind function. First, we used multiple approaches to identify and characterize specific domains within the protein that confer repressor or activator ability. Currently, little is known about the presence of activation or repression domains within Ind. Here, we show that transcriptional repression by Ind requires multiple conserved domains within the protein, and that Ind has a transcriptional activation domain. Specifically, we have identified a novel domain, the Pst domain, that has transcriptional repression ability and appears to act independent of interaction with the co-repressor Groucho. This domain is highly conserved among insect species, but is not found in vertebrate Gsh class homeodomain proteins. Second, we show that Ind can and does repress vnd expression, but does so in a stage specific manner. We conclude from this that the function of Ind in regulating vnd expression is one of refinement and maintenance of the dorsal border.

Skin and scales of teleost fish: Simple structure but high performance and multiple functions

NASA Astrophysics Data System (ADS)

Vernerey, Franck J.; Barthelat, Francois

2014-08-01

Natural and man-made structural materials perform similar functions such as structural support or protection. Therefore they rely on the same types of properties: strength, robustness, lightweight. Nature can therefore provide a significant source of inspiration for new and alternative engineering designs. We report here some results regarding a very common, yet largely unknown, type of biological material: fish skin. Within a thin, flexible and lightweight layer, fish skins display a variety of strain stiffening and stabilizing mechanisms which promote multiple functions such as protection, robustness and swimming efficiency. We particularly discuss four important features pertaining to scaled skins: (a) a strongly elastic tensile behavior that is independent from the presence of rigid scales, (b) a compressive response that prevents buckling and wrinkling instabilities, which are usually predominant for thin membranes, (c) a bending response that displays nonlinear stiffening mechanisms arising from geometric constraints between neighboring scales and (d) a robust structure that preserves the above characteristics upon the loss or damage of structural elements. These important properties make fish skin an attractive model for the development of very thin and flexible armors and protective layers, especially when combined with the high penetration resistance of individual scales. Scaled structures inspired by fish skin could find applications in ultra-light and flexible armor systems, flexible electronics or the design of smart and adaptive morphing structures for aerospace vehicles.

Calcium as a signal integrator in developing epithelial tissues.

PubMed

Brodskiy, Pavel A; Zartman, Jeremiah J

2018-05-16

Decoding how tissue properties emerge across multiple spatial and temporal scales from the integration of local signals is a grand challenge in quantitative biology. For example, the collective behavior of epithelial cells is critical for shaping developing embryos. Understanding how epithelial cells interpret a diverse range of local signals to coordinate tissue-level processes requires a systems-level understanding of development. Integration of multiple signaling pathways that specify cell signaling information requires second messengers such as calcium ions. Increasingly, specific roles have been uncovered for calcium signaling throughout development. Calcium signaling regulates many processes including division, migration, death, and differentiation. However, the pleiotropic and ubiquitous nature of calcium signaling implies that many additional functions remain to be discovered. Here we review a selection of recent studies to highlight important insights into how multiple signals are transduced by calcium transients in developing epithelial tissues. Quantitative imaging and computational modeling have provided important insights into how calcium signaling integration occurs. Reverse-engineering the conserved features of signal integration mediated by calcium signaling will enable novel approaches in regenerative medicine and synthetic control of morphogenesis.

Gender-specific association between dietary acid load and total lean body mass and its dependency on protein intake in seniors

USDA-ARS?s Scientific Manuscript database

Background: Sarcopenia, the age-related decline of muscle mass, is one of the most important causes of loss of physical function and falls in seniors. Causes of sarcopenia are multiple, but there is evidence that diet-related mild metabolic acidosis may play a role in the development of skeletal mus...

A basic helix-loop-helix transcription factor, PhFBH4, regulates flower senescence by modulating ethylene biosynthesis pathway in petunia

USDA-ARS?s Scientific Manuscript database

The basic helix-loop-helix (bHLH) transcription factors (TFs) play important roles in regulating multiple biological processes in plants. However, there are few reports about the function of bHLHs in flower senescence. In this study, a bHLH TF, PhFBH4, was found to be dramatically upregulated during...

Free energy landscape and transition pathways from Watson-Crick to Hoogsteen base pairing in free duplex DNA.

PubMed

Yang, Changwon; Kim, Eunae; Pak, Youngshang

2015-09-18

Houghton (HG) base pairing plays a central role in the DNA binding of proteins and small ligands. Probing detailed transition mechanism from Watson-Crick (WC) to HG base pair (bp) formation in duplex DNAs is of fundamental importance in terms of revealing intrinsic functions of double helical DNAs beyond their sequence determined functions. We investigated a free energy landscape of a free B-DNA with an adenosine-thymine (A-T) rich sequence to probe its conformational transition pathways from WC to HG base pairing. The free energy landscape was computed with a state-of-art two-dimensional umbrella molecular dynamics simulation at the all-atom level. The present simulation showed that in an isolated duplex DNA, the spontaneous transition from WC to HG bp takes place via multiple pathways. Notably, base flipping into the major and minor grooves was found to play an important role in forming these multiple transition pathways. This finding suggests that naked B-DNA under normal conditions has an inherent ability to form HG bps via spontaneous base opening events. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Why is the correlation between gene importance and gene evolutionary rate so weak?

PubMed

Wang, Zhi; Zhang, Jianzhi

2009-01-01

One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful despite the weakness of the correlation.

A Portable Farmland Information Collection System with Multiple Sensors.

PubMed

Zhang, Jianfeng; Hu, Jinyang; Huang, Lvwen; Zhang, Zhiyong; Ma, Yimian

2016-10-22

Precision agriculture is the trend of modern agriculture, and it is also one of the important ways to realize the sustainable development of agriculture. In order to meet the production requirements of precision agriculture-efficient use of agricultural resources, and improving the crop yields and quality-some necessary field information in crop growth environment needs to be collected and monitored. In this paper, a farmland information collection system is developed, which includes a portable farmland information collection device based on STM32 (a 32-bit comprehensive range of microcontrollers based on ARM Crotex-M3), a remote server and a mobile phone APP. The device realizes the function of portable and mobile collecting of multiple parameters farmland information, such as chlorophyll content of crop leaves, air temperature, air humidity, and light intensity. UM220-III (Unicore Communication Inc., Beijing, China) is used to realize the positioning based on BDS/GPS (BeiDou Navigation Satellite System, BDS/Global Positioning System, GPS) dual-mode navigation and positioning system, and the CDMA (Code Division Multiple Access, CDMA) wireless communication module is adopted to realize the real-time remote transmission. The portable multi-function farmland information collection system is real-time, accurate, and easy to use to collect farmland information and multiple information parameters of crops.

A Portable Farmland Information Collection System with Multiple Sensors

PubMed Central

Zhang, Jianfeng; Hu, Jinyang; Huang, Lvwen; Zhang, Zhiyong; Ma, Yimian

2016-01-01

Precision agriculture is the trend of modern agriculture, and it is also one of the important ways to realize the sustainable development of agriculture. In order to meet the production requirements of precision agriculture—efficient use of agricultural resources, and improving the crop yields and quality—some necessary field information in crop growth environment needs to be collected and monitored. In this paper, a farmland information collection system is developed, which includes a portable farmland information collection device based on STM32 (a 32-bit comprehensive range of microcontrollers based on ARM Crotex-M3), a remote server and a mobile phone APP. The device realizes the function of portable and mobile collecting of multiple parameters farmland information, such as chlorophyll content of crop leaves, air temperature, air humidity, and light intensity. UM220-III (Unicore Communication Inc., Beijing, China) is used to realize the positioning based on BDS/GPS (BeiDou Navigation Satellite System, BDS/Global Positioning System, GPS) dual-mode navigation and positioning system, and the CDMA (Code Division Multiple Access, CDMA) wireless communication module is adopted to realize the real-time remote transmission. The portable multi-function farmland information collection system is real-time, accurate, and easy to use to collect farmland information and multiple information parameters of crops. PMID:27782076

Biocrust-forming mosses mitigate the negative impacts of increasing aridity on ecosystem multifunctionality in drylands.

PubMed

Delgado-Baquerizo, Manuel; Maestre, Fernando T; Eldridge, David J; Bowker, Matthew A; Ochoa, Victoria; Gozalo, Beatriz; Berdugo, Miguel; Val, James; Singh, Brajesh K

2016-03-01

The increase in aridity predicted with climate change will have a negative impact on the multiple functions and services (multifunctionality) provided by dryland ecosystems worldwide. In these ecosystems, soil communities dominated by mosses, lichens and cyanobacteria (biocrusts) play a key role in supporting multifunctionality. However, whether biocrusts can buffer the negative impacts of aridity on important biogeochemical processes controlling carbon (C), nitrogen (N), and phosphorus (P) pools and fluxes remains largely unknown. Here, we conducted an empirical study, using samples from three continents (North America, Europe and Australia), to evaluate how the increase in aridity predicted by climate change will alter the capacity of biocrust-forming mosses to modulate multiple ecosystem processes related to C, N and P cycles. Compared with soil surfaces lacking biocrusts, biocrust-forming mosses enhanced multiple functions related to C, N and P cycling and storage in semiarid and arid, but not in humid and dry-subhumid, environments. Most importantly, we found that the relative positive effects of biocrust-forming mosses on multifunctionality compared with bare soil increased with increasing aridity. These results were mediated by plant cover and the positive effects exerted by biocrust-forming mosses on the abundance of soil bacteria and fungi. Our findings provide strong evidence that the maintenance of biocrusts is crucial to buffer negative effects of climate change on multifunctionality in global drylands. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

The putative interplay between DJ-1/NRF2 and Dimethyl Fumarate: A potentially important pharmacological target.

PubMed

Vavougios, George; Zarogiannis, Sotirios G; Doskas, Triantafylos

2018-04-01

Recent research has outlined that Dimethyl Fumarate (DMF) functions as a gene regulator via multiple pathways, critical among which is the NRF2 cytoprotective cascade. PARK7/DJ-1 is a multifunctional protein that acts as a redox sensor and effector of multiple cytoprotective pathways, including NRF2. Specifically, it prevents the association of NRF2 with its inhibitor KEAP1, allowing NRF2 to enter the nucleus and mediate cytoprotective and antioxidant cascades. It is our hypothesis that while the NRF2-KEAP1 inhibitory complex is reported the main pharmacological target for DMF's NRF dependent functions, no study to date has explored the effects of DMF on DJ-1's expression, and vice-versa, the possibility of a regulatory inadequacy in the upstream, oxidant-responsive DJ-1 activator of the NRF2 cascade. Copyright © 2018 Elsevier B.V. All rights reserved.

MSDB: A Comprehensive Database of Simple Sequence Repeats

PubMed Central

Avvaru, Akshay Kumar; Saxena, Saketh; Mishra, Rakesh Kumar

2017-01-01

Abstract Microsatellites, also known as Simple Sequence Repeats (SSRs), are short tandem repeats of 1–6 nt motifs present in all genomes, particularly eukaryotes. Besides their usefulness as genome markers, SSRs have been shown to perform important regulatory functions, and variations in their length at coding regions are linked to several disorders in humans. Microsatellites show a taxon-specific enrichment in eukaryotic genomes, and some may be functional. MSDB (Microsatellite Database) is a collection of >650 million SSRs from 6,893 species including Bacteria, Archaea, Fungi, Plants, and Animals. This database is by far the most exhaustive resource to access and analyze SSR data of multiple species. In addition to exploring data in a customizable tabular format, users can view and compare the data of multiple species simultaneously using our interactive plotting system. MSDB is developed using the Django framework and MySQL. It is freely available at http://tdb.ccmb.res.in/msdb. PMID:28854643

Determination of the core promoter regions of the Saccharomyces cerevisiae RPS3 gene.

PubMed

Joo, Yoo Jin; Kim, Jin-Ha; Baek, Joung Hee; Seong, Ki Moon; Lee, Jae Yung; Kim, Joon

2009-01-01

Ribosomal protein genes (RPG), which are scattered throughout the genomes of all eukaryotes, are subjected to coordinated expression. In yeast, the expression of RPGs is highly regulated, mainly at the transcriptional level. Recent research has found that many ribosomal proteins (RPs) function in multiple processes in addition to protein synthesis. Therefore, detailed knowledge of promoter architecture as well as gene regulation is important in understanding the multiple cellular processes mediated by RPGs. In this study, we investigated the functional architecture of the yeast RPS3 promoter and identified many putative cis-elements. Using beta-galactosidase reporter analysis and EMSA, the core promoter of RPS3 containing UASrpg and T-rich regions was corroborated. Moreover, the promoter occupancy of RPS3 by three transcription factors was confirmed. Taken together, our results further the current understanding of the promoter architecture and trans-elements of the Saccharomyces cerevisiae RPS3 gene.

Quantitative multimodality imaging in cancer research and therapy.

PubMed

Yankeelov, Thomas E; Abramson, Richard G; Quarles, C Chad

2014-11-01

Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein.

Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies

PubMed Central

Kober, Hedy; Barrett, Lisa Feldman; Joseph, Josh; Bliss-Moreau, Eliza; Lindquist, Kristen; Wager, Tor D.

2009-01-01

We performed an updated quantitative meta-analysis of 162 neuroimaging studies of emotion using a novel multi-level kernel-based approach, focusing on locating brain regions consistently activated in emotional tasks and their functional organization into distributed functional groups, independent of semantically defined emotion category labels (e.g., “anger,” “fear”). Such brain-based analyses are critical if our ways of labeling emotions are to be evaluated and revised based on consistency with brain data. Consistent activations were limited to specific cortical sub-regions, including multiple functional areas within medial, orbital, and inferior lateral frontal cortices. Consistent with a wealth of animal literature, multiple subcortical activations were identified, including amygdala, ventral striatum, thalamus, hypothalamus, and periaqueductal gray. We used multivariate parcellation and clustering techniques to identify groups of co-activated brain regions across studies. These analyses identified six distributed functional groups, including medial and lateral frontal groups, two posterior cortical groups, and paralimbic and core limbic/brainstem groups. These functional groups provide information on potential organization of brain regions into large-scale networks. Specific follow-up analyses focused on amygdala, periaqueductal gray (PAG), and hypothalamic (Hy) activations, and identified frontal cortical areas co-activated with these core limbic structures. While multiple areas of frontal cortex co-activated with amygdala sub-regions, a specific region of dorsomedial prefrontal cortex (dmPFC, Brodmann’s Area 9/32) was the only area co-activated with both PAG and Hy. Subsequent mediation analyses were consistent with a pathway from dmPFC through PAG to Hy. These results suggest that medial frontal areas are more closely associated with core limbic activation than their lateral counterparts, and that dmPFC may play a particularly important role in the cognitive generation of emotional states. PMID:18579414

A slow-releasing form of prostacyclin agonist (ONO1301SR) enhances endogenous secretion of multiple cardiotherapeutic cytokines and improves cardiac function in a rapid-pacing-induced model of canine heart failure.

PubMed

Shirasaka, Tomonori; Miyagawa, Shigeru; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Nakatani, Satoshi; Sakai, Yoshiki; Daimon, Takashi; Okita, Yutaka; Sawa, Yoshiki

2013-08-01

Cardiac functional deterioration in dilated cardiomyopathy (DCM) is known to be reversed by intramyocardial up-regulation of multiple cardioprotective factors, whereas a prostacyclin analog, ONO1301, has been shown to paracrinally activate interstitial cells to release a variety of protective factors. We here hypothesized that intramyocardial delivery of a slow-releasing form of ONO1301 (ONO1301SR) might activate regional myocardium to up-regulate cardiotherapeutic factors, leading to regional and global functional recovery in DCM. ONO1301 elevated messenger RNA and protein level of hepatocyte growth factor, vascular endothelial growth factor, and stromal-derived factor-1 of normal human dermal fibroblasts in a dose-dependent manner in vitro. Intramyocardial delivery of ONO1301SR, which is ONO1301 mixed with polylactic and glycolic acid polymer (PLGA), but not that of PLGA only, yielded significant global functional recovery in a canine rapid pacing-induced DCM model, assessed by echocardiography and cardiac catheterization (n = 5 each). Importantly, speckle-tracking echocardiography unveiled significant regional functional recovery in the ONO1301-delivered territory, consistent to significantly increased vascular density, reduced interstitial collagen accumulation, attenuated myocyte hypertrophy, and reversed mitochondrial structure in the corresponding area. Intramyocardial delivery of ONO1301SR, which is a PLGA-coated slow-releasing form of ONO1301, up-regulated multiple cardiotherapeutic factors in the injected territory, leading to region-specific reverse left ventricular remodeling and consequently a global functional recovery in a rapid-pacing-induced canine DCM model, warranting a further preclinical study to optimize this novel drug-delivery system to treat DCM. Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Orphan Nuclear Receptors as Targets for Drug Development

PubMed Central

Mukherjee, Subhajit

2012-01-01

Orphan nuclear receptors regulate diverse biological processes. These important molecules are ligand-activated transcription factors that act as natural sensors for a wide range of steroid hormones and xenobiotic ligands. Because of their importance in regulating various novel signaling pathways, recent research has focused on identifying xenobiotics targeting these receptors for the treatment of multiple human diseases. In this review, we will highlight these receptors in several physiologic and pathophysiologic actions and demonstrate how their functions can be exploited for the successful development of newer drugs. PMID:20372994

Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells.

PubMed

Halaidych, Oleh V; Freund, Christian; van den Hil, Francijna; Salvatori, Daniela C F; Riminucci, Mara; Mummery, Christine L; Orlova, Valeria V

2018-05-08

Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Association between Social Activities and Cognitive Function among the Elderly in China: A Cross-Sectional Study.

PubMed

Fu, Chang; Li, Zhen; Mao, Zongfu

2018-01-30

Participation in social activities is one of important factors for older adults' health. The present study aims to examine the cross-sectional association between social activities and cognitive function among Chinese elderly. A total of 8966 individuals aged 60 and older from the 2015 China Health and Retirement Longitudinal Study were obtained for this study. Telephone interviews of cognitive status, episodic memory, and visuospatial abilities were assessed by questionnaire. We used the sum of all three of the above measures to represent the respondent's cognitive status as a whole. Types and frequencies of participation in social groups were used to measure social activities. Multiple linear regression analysis was used to explore the relationship between social activities and cognitive function. After adjustment for demographics, smoking, drinking, depression, hypertension, diabetes, basic activities of daily living, instrumental activities of daily living, and self-rated health, multiple linear regression analysis revealed that interaction with friends, participating in hobby groups, and sports groups were associated with better cognitive function among both men and women ( p < 0.05); doing volunteer work was associated with better cognitive function among women but not among men ( p < 0.05). These findings suggest that there is a cross-sectional association between participation in social activities and cognitive function among Chinese elderly. Longitudinal studies are needed to examine the effects of social activities on cognitive function.

Association between Social Activities and Cognitive Function among the Elderly in China: A Cross-Sectional Study

PubMed Central

Fu, Chang; Li, Zhen; Mao, Zongfu

2018-01-01

Participation in social activities is one of important factors for older adults’ health. The present study aims to examine the cross-sectional association between social activities and cognitive function among Chinese elderly. A total of 8966 individuals aged 60 and older from the 2015 China Health and Retirement Longitudinal Study were obtained for this study. Telephone interviews of cognitive status, episodic memory, and visuospatial abilities were assessed by questionnaire. We used the sum of all three of the above measures to represent the respondent’s cognitive status as a whole. Types and frequencies of participation in social groups were used to measure social activities. Multiple linear regression analysis was used to explore the relationship between social activities and cognitive function. After adjustment for demographics, smoking, drinking, depression, hypertension, diabetes, basic activities of daily living, instrumental activities of daily living, and self-rated health, multiple linear regression analysis revealed that interaction with friends, participating in hobby groups, and sports groups were associated with better cognitive function among both men and women (p < 0.05); doing volunteer work was associated with better cognitive function among women but not among men (p < 0.05). These findings suggest that there is a cross-sectional association between participation in social activities and cognitive function among Chinese elderly. Longitudinal studies are needed to examine the effects of social activities on cognitive function. PMID:29385773

Chemical Mapping of Essential Oils, Flavonoids and Carotenoids in Citrus Peels by Raman Microscopy.

PubMed

Yang, Ying; Wang, Xiaohe; Zhao, Chengying; Tian, Guifang; Zhang, Hua; Xiao, Hang; He, Lili; Zheng, Jinkai

2017-12-01

Citrus peels, by-products in large quantity, are rich in various functional and beneficial components which have wide applications. Chemical analysis of these components in citrus peels is an important step to determine the usefulness of the by-products for further applications. In this study, we explored Raman microscopy for rapid, nondestructive, and in situ chemical mapping of multiple main functional components from citrus peels. The relative amount and distribution in different locations (flavedo, albedo, and longitudinal section) of 3 main functional components (essential oils, carotenoids, and flavonoids) in citrus peels were systematically investigated. The distribution profiles of these components were heterogeneous on the peels and varied between different species of citrus peels. Essential oil was found mainly existed in the oil glands, while carotenoids were in the complementary location. Some flavonoids were observed in the oil glands. This study showed the capability of Raman microscopy for rapid and nondestructive analysis of multiple bio-components without extraction from plants. The information obtained from this study would assist the better production and application of the functional and beneficial components from citrus by products in an effective and sustainable manner. This study indicated the capability of Raman microscopy for rapid and nondestructive analysis of multiple bioactive components in plant tissues. The information obtained from the study would be valuable for developing effective and sustainable strategy of utilization of citrus peels for further applications. © 2017 Institute of Food Technologists®.

Non-linear molecular pattern classification using molecular beacons with multiple targets.

PubMed

Lee, In-Hee; Lee, Seung Hwan; Park, Tai Hyun; Zhang, Byoung-Tak

2013-12-01

In vitro pattern classification has been highlighted as an important future application of DNA computing. Previous work has demonstrated the feasibility of linear classifiers using DNA-based molecular computing. However, complex tasks require non-linear classification capability. Here we design a molecular beacon that can interact with multiple targets and experimentally shows that its fluorescent signals form a complex radial-basis function, enabling it to be used as a building block for non-linear molecular classification in vitro. The proposed method was successfully applied to solving artificial and real-world classification problems: XOR and microRNA expression patterns. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors*

PubMed Central

Smith, Jeffrey S.; Rajagopal, Sudarshan

2016-01-01

The β-arrestins (βarrs) are versatile, multifunctional adapter proteins that are best known for their ability to desensitize G protein-coupled receptors (GPCRs), but also regulate a diverse array of cellular functions. To signal in such a complex fashion, βarrs adopt multiple conformations and are regulated at multiple levels to differentially activate downstream pathways. Recent structural studies have demonstrated that βarrs have a conserved structure and activation mechanism, with plasticity of their structural fold, allowing them to adopt a wide array of conformations. Novel roles for βarrs continue to be identified, demonstrating the importance of these dynamic regulators of cellular signaling. PMID:26984408

Parametric Bayesian priors and better choice of negative examples improve protein function prediction.

PubMed

Youngs, Noah; Penfold-Brown, Duncan; Drew, Kevin; Shasha, Dennis; Bonneau, Richard

2013-05-01

Computational biologists have demonstrated the utility of using machine learning methods to predict protein function from an integration of multiple genome-wide data types. Yet, even the best performing function prediction algorithms rely on heuristics for important components of the algorithm, such as choosing negative examples (proteins without a given function) or determining key parameters. The improper choice of negative examples, in particular, can hamper the accuracy of protein function prediction. We present a novel approach for choosing negative examples, using a parameterizable Bayesian prior computed from all observed annotation data, which also generates priors used during function prediction. We incorporate this new method into the GeneMANIA function prediction algorithm and demonstrate improved accuracy of our algorithm over current top-performing function prediction methods on the yeast and mouse proteomes across all metrics tested. Code and Data are available at: http://bonneaulab.bio.nyu.edu/funcprop.html

Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

PubMed

Coulthard, Elizabeth J; Bogacz, Rafal; Javed, Shazia; Mooney, Lucy K; Murphy, Gillian; Keeley, Sophie; Whone, Alan L

2012-12-01

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

Functional traits in agriculture: agrobiodiversity and ecosystem services.

PubMed

Wood, Stephen A; Karp, Daniel S; DeClerck, Fabrice; Kremen, Claire; Naeem, Shahid; Palm, Cheryl A

2015-09-01

Functional trait research has led to greater understanding of the impacts of biodiversity in ecosystems. Yet, functional trait approaches have not been widely applied to agroecosystems and understanding of the importance of agrobiodiversity remains limited to a few ecosystem processes and services. To improve this understanding, we argue here for a functional trait approach to agroecology that adopts recent advances in trait research for multitrophic and spatially heterogeneous ecosystems. We suggest that trait values should be measured across environmental conditions and agricultural management regimes to predict how ecosystem services vary with farm practices and environment. This knowledge should be used to develop management strategies that can be easily implemented by farmers to manage agriculture to provide multiple ecosystem services. Copyright © 2015 Elsevier Ltd. All rights reserved.

Determinants of RNA binding and translational repression by the Bicaudal-C regulatory protein.

PubMed

Zhang, Yan; Park, Sookhee; Blaser, Susanne; Sheets, Michael D

2014-03-14

Bicaudal-C (Bic-C) RNA binding proteins function as important translational repressors in multiple biological contexts within metazoans. However, their RNA binding sites are unknown. We recently demonstrated that Bic-C functions in spatially regulated translational repression of the xCR1 mRNA during Xenopus development. This repression contributes to normal development by confining the xCR1 protein, a regulator of key signaling pathways, to specific cells of the embryo. In this report, we combined biochemical approaches with in vivo mRNA reporter assays to define the minimal Bic-C target site within the xCR1 mRNA. This 32-nucleotide Bic-C target site is predicted to fold into a stem-loop secondary structure. Mutational analyses provided evidence that this stem-loop structure is important for Bic-C binding. The Bic-C target site was sufficient for Bic-C mediated repression in vivo. Thus, we describe the first RNA binding site for a Bic-C protein. This identification provides an important step toward understanding the mechanisms by which evolutionarily conserved Bic-C proteins control cellular function in metazoans.

Building a functional multiple intelligences theory to advance educational neuroscience

PubMed Central

Cerruti, Carlo

2013-01-01

A key goal of educational neuroscience is to conduct constrained experimental research that is theory-driven and yet also clearly related to educators’ complex set of questions and concerns. However, the fields of education, cognitive psychology, and neuroscience use different levels of description to characterize human ability. An important advance in research in educational neuroscience would be the identification of a cognitive and neurocognitive framework at a level of description relatively intuitive to educators. I argue that the theory of multiple intelligences (MI; Gardner, 1983), a conception of the mind that motivated a past generation of teachers, may provide such an opportunity. I criticize MI for doing little to clarify for teachers a core misunderstanding, specifically that MI was only an anatomical map of the mind but not a functional theory that detailed how the mind actually processes information. In an attempt to build a “functional MI” theory, I integrate into MI basic principles of cognitive and neural functioning, namely interregional neural facilitation and inhibition. In so doing I hope to forge a path toward constrained experimental research that bears upon teachers’ concerns about teaching and learning. PMID:24391613

Prohibitin (PHB) roles in granulosa cell physiology

PubMed Central

Chowdhury, Indrajit; Thomas, Kelwyn; Thompson, Winston E.

2015-01-01

Ovarian granulosa cells (GC) play an important role in the growth and development of the follicle in the process known as folliculogenesis. In the present review, we focus on the recent developments in prohibitin (PHB) research in relation to GC physiological functions. PHB is a member of highly conserved eukaryotic protein family containing the repressor of estrogen activity (REA)/stomatin/prohibitin/flotillin/HflK/C (SPFH) domain [also known as the PHB domain] found in divergent species from prokaryotes to eukaryotes. PHB is ubiquitously expressed either in circulating free form or is present in multiple cellular compartments including mitochondria, nucleus and plasma membrane. In mitochondria, PHB is anchored to the mitochondrial inner membrane (IMM), and form complexes with the ATPases Associated with diverse cellular Activities (m-AAA) proteases. PHB continuously shuttles between the mitochondria, cytosol and nucleus. In the nucleus, PHB interacts with various transcription factors and modulate transcriptional activity directly or through interactions with chromatin remodeling proteins. Multiple functions have been attributed to the mitochondrial and nuclear prohibitin complexes such as cellular differentiation, anti-proliferation, morphogenesis and maintaining the functional integrity of the mitochondria. However, to date, the regulation of PHB expression patterns and GC physiological functions are not completely understood. PMID:26496733

Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

PubMed

Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

2017-04-12

Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We found that social recognition memory is consolidated through CREB-meditated gene expression in the hippocampus, medial prefrontal cortex, anterior cingulate cortex (ACC), and amygdala. Importantly, network analyses based on c-fos expression suggest that functional connectivity of these four brain regions with other brain regions is increased with time spent in social investigation toward the generation of brain networks to consolidate social recognition memory. Furthermore, our findings suggest that hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. Copyright © 2017 the authors 0270-6474/17/374103-14$15.00/0.

Nutrient controls on biocomplexity of mangrove ecosystems

USGS Publications Warehouse

McKee, Karen L.

2004-01-01

Mangrove forests are important coastal ecosystems that provide a variety of ecological and societal services. These intertidal, tree-dominated communities along tropical coastlines are often described as “simple systems,” compared to other tropical forests with larger numbers of plant species and multiple understory strata; however, mangrove ecosystems have complex trophic structures, and organisms exhibit unique physiological, morphological, and behavioral adaptations to environmental conditions characteristic of the land-sea interface. Biogeochemical functioning of mangrove forests is also controlled by interactions among the microbial, plant, and animal communities and feedback linkages mediated by hydrology and other forcing functions. Scientists with the U.S. Geological Survey (USGS) at the National Wetlands Research Center are working to understand more fully the impact of nutrient variability on these delicate and important ecosystems.

Sumoylation promotes optimal APC/C Activation and Timely Anaphase.

PubMed

Lee, Christine C; Li, Bing; Yu, Hongtao; Matunis, Michael J

2018-03-08

The Anaphase Promoting Complex/Cyclosome (APC/C) is a ubiquitin E3 ligase that functions as the gatekeeper to mitotic exit. APC/C activity is controlled by an interplay of multiple pathways during mitosis, including the spindle assembly checkpoint (SAC), that are not yet fully understood. Here, we show that sumoylation of the APC4 subunit of the APC/C peaks during mitosis and is critical for timely APC/C activation and anaphase onset. We have also identified a functionally important SUMO interacting motif in the cullin-homology domain of APC2 located near the APC4 sumoylation sites and APC/C catalytic core. Our findings provide evidence of an important regulatory role for SUMO modification and binding in affecting APC/C activation and mitotic exit. © 2018, Lee et al.

Neural control of renal function in health and disease.

PubMed

DiBona, G F

1994-04-01

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing.

PubMed

Gökirmak, Tufan; Campanale, Joseph P; Reitzel, Adam M; Shipp, Lauren E; Moy, Gary W; Hamdoun, Amro

2016-06-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. Copyright © 2016 the American Physiological Society.

Functional diversification of sea urchin ABCC1 (MRP1) by alternative splicing

PubMed Central

Gökirmak, Tufan; Campanale, Joseph P.; Reitzel, Adam M.; Shipp, Lauren E.; Moy, Gary W.

2016-01-01

The multidrug resistance protein (MRP) family encodes a diverse repertoire of ATP-binding cassette (ABC) transporters with multiple roles in development, disease, and homeostasis. Understanding MRP evolution is central to unraveling their roles in these diverse processes. Sea urchins occupy an important phylogenetic position for understanding the evolution of vertebrate proteins and have been an important invertebrate model system for study of ABC transporters. We used phylogenetic analyses to examine the evolution of MRP transporters and functional approaches to identify functional forms of sea urchin MRP1 (also known as SpABCC1). SpABCC1, the only MRP homolog in sea urchins, is co-orthologous to human MRP1, MRP3, and MRP6 (ABCC1, ABCC3, and ABCC6) transporters. However, efflux assays revealed that alternative splicing of exon 22, a region critical for substrate interactions, could diversify functions of sea urchin MRP1. Phylogenetic comparisons also indicate that while MRP1, MRP3, and MRP6 transporters potentially arose from a single transporter in basal deuterostomes, alternative splicing appears to have been the major mode of functional diversification in invertebrates, while duplication may have served a more important role in vertebrates. These results provide a deeper understanding of the evolutionary origins of MRP transporters and the potential mechanisms used to diversify their functions in different groups of animals. PMID:27053522

Multiple Assembly Rules Drive the Co-occurrence of Orthopteran and Plant Species in Grasslands: Combining Network, Functional and Phylogenetic Approaches

PubMed Central

Fournier, Bertrand; Mouly, Arnaud; Gillet, François

2016-01-01

Understanding the factors underlying the co-occurrence of multiple species remains a challenge in ecology. Biotic interactions, environmental filtering and neutral processes are among the main mechanisms evoked to explain species co-occurrence. However, they are most often studied separately or even considered as mutually exclusive. This likely hampers a more global understanding of species assembly. Here, we investigate the general hypothesis that the structure of co-occurrence networks results from multiple assembly rules and its potential implications for grassland ecosystems. We surveyed orthopteran and plant communities in 48 permanent grasslands of the French Jura Mountains and gathered functional and phylogenetic data for all species. We constructed a network of plant and orthopteran species co-occurrences and verified whether its structure was modular or nested. We investigated the role of all species in the structure of the network (modularity and nestedness). We also investigated the assembly rules driving the structure of the plant-orthopteran co-occurrence network by using null models on species functional traits, phylogenetic relatedness and environmental conditions. We finally compared our results to abundance-based approaches. We found that the plant-orthopteran co-occurrence network had a modular organization. Community assembly rules differed among modules for plants while interactions with plants best explained the distribution of orthopterans into modules. Few species had a disproportionately high positive contribution to this modular organization and are likely to have a key importance to modulate future changes. The impact of agricultural practices was restricted to some modules (3 out of 5) suggesting that shifts in agricultural practices might not impact the entire plant-orthopteran co-occurrence network. These findings support our hypothesis that multiple assembly rules drive the modular structure of the plant-orthopteran network. This modular structure is likely to play a key role in the response of grassland ecosystems to future changes by limiting the impact of changes in agricultural practices such as intensification to some modules leaving species from other modules poorly impacted. The next step is to understand the importance of this modular structure for the long-term maintenance of grassland ecosystem structure and functions as well as to develop tools to integrate network structure into models to improve their capacity to predict future changes. PMID:27582754

An ensemble framework for clustering protein-protein interaction networks.

PubMed

Asur, Sitaram; Ucar, Duygu; Parthasarathy, Srinivasan

2007-07-01

Protein-Protein Interaction (PPI) networks are believed to be important sources of information related to biological processes and complex metabolic functions of the cell. The presence of biologically relevant functional modules in these networks has been theorized by many researchers. However, the application of traditional clustering algorithms for extracting these modules has not been successful, largely due to the presence of noisy false positive interactions as well as specific topological challenges in the network. In this article, we propose an ensemble clustering framework to address this problem. For base clustering, we introduce two topology-based distance metrics to counteract the effects of noise. We develop a PCA-based consensus clustering technique, designed to reduce the dimensionality of the consensus problem and yield informative clusters. We also develop a soft consensus clustering variant to assign multifaceted proteins to multiple functional groups. We conduct an empirical evaluation of different consensus techniques using topology-based, information theoretic and domain-specific validation metrics and show that our approaches can provide significant benefits over other state-of-the-art approaches. Our analysis of the consensus clusters obtained demonstrates that ensemble clustering can (a) produce improved biologically significant functional groupings; and (b) facilitate soft clustering by discovering multiple functional associations for proteins. Supplementary data are available at Bioinformatics online.

Identifying and exploiting trait-relevant tissues with multiple functional annotations in genome-wide association studies

PubMed Central

Zhang, Shujun

2018-01-01

Genome-wide association studies (GWASs) have identified many disease associated loci, the majority of which have unknown biological functions. Understanding the mechanism underlying trait associations requires identifying trait-relevant tissues and investigating associations in a trait-specific fashion. Here, we extend the widely used linear mixed model to incorporate multiple SNP functional annotations from omics studies with GWAS summary statistics to facilitate the identification of trait-relevant tissues, with which to further construct powerful association tests. Specifically, we rely on a generalized estimating equation based algorithm for parameter inference, a mixture modeling framework for trait-tissue relevance classification, and a weighted sequence kernel association test constructed based on the identified trait-relevant tissues for powerful association analysis. We refer to our analytic procedure as the Scalable Multiple Annotation integration for trait-Relevant Tissue identification and usage (SMART). With extensive simulations, we show how our method can make use of multiple complementary annotations to improve the accuracy for identifying trait-relevant tissues. In addition, our procedure allows us to make use of the inferred trait-relevant tissues, for the first time, to construct more powerful SNP set tests. We apply our method for an in-depth analysis of 43 traits from 28 GWASs using tissue-specific annotations in 105 tissues derived from ENCODE and Roadmap. Our results reveal new trait-tissue relevance, pinpoint important annotations that are informative of trait-tissue relationship, and illustrate how we can use the inferred trait-relevant tissues to construct more powerful association tests in the Wellcome trust case control consortium study. PMID:29377896

The Langer-Improved Wald Test for DIF Testing with Multiple Groups: Evaluation and Comparison to Two-Group IRT

ERIC Educational Resources Information Center

Woods, Carol M.; Cai, Li; Wang, Mian

2013-01-01

Differential item functioning (DIF) occurs when the probability of responding in a particular category to an item differs for members of different groups who are matched on the construct being measured. The identification of DIF is important for valid measurement. This research evaluates an improved version of Lord's chi [superscript 2]…

A Conceptual Framework for the Assessment of Multiple Functions of Agro-Ecosystems: A Case Study of Tras-os-Montes Olive Groves

ERIC Educational Resources Information Center

Fleskens, Luuk; Duarte, Filomena; Eicher, Irmgard

2009-01-01

Multifunctionality in agriculture has received a lot of attention the last decade from researchers and policy-makers alike, perhaps most notably evidenced by the important changes made to the EU's Common Agricultural Policy. While the concept has been embraced by environmentalists envisioning positive impulses for decoupling and a range of local…

Research Notes - An Introduction to Openness and Evolvability Assessment

DTIC Science & Technology

2016-08-01

importance of different business and technical characteristics that combine to achieve an open solution. The complexity of most large-scale systems of...process characteristic)  Granularity of the architecture (size of functional blocks)  Modularity (cohesion and coupling)  Support for multiple...Description)  OV-3 (Operational Information Exchange Matrix)  SV-1 (Systems Interface Description)  TV-1 ( Technical Standards Profile). Note that there

Actin filaments-A target for redox regulation.

PubMed

Wilson, Carlos; Terman, Jonathan R; González-Billault, Christian; Ahmed, Giasuddin

2016-10-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through noncovalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates-the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL-and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Multilayer modeling and analysis of human brain networks

PubMed Central

2017-01-01

Abstract Understanding how the human brain is structured, and how its architecture is related to function, is of paramount importance for a variety of applications, including but not limited to new ways to prevent, deal with, and cure brain diseases, such as Alzheimer’s or Parkinson’s, and psychiatric disorders, such as schizophrenia. The recent advances in structural and functional neuroimaging, together with the increasing attitude toward interdisciplinary approaches involving computer science, mathematics, and physics, are fostering interesting results from computational neuroscience that are quite often based on the analysis of complex network representation of the human brain. In recent years, this representation experienced a theoretical and computational revolution that is breaching neuroscience, allowing us to cope with the increasing complexity of the human brain across multiple scales and in multiple dimensions and to model structural and functional connectivity from new perspectives, often combined with each other. In this work, we will review the main achievements obtained from interdisciplinary research based on magnetic resonance imaging and establish de facto, the birth of multilayer network analysis and modeling of the human brain. PMID:28327916

Actin filaments – a target for redox regulation

PubMed Central

Wilson, Carlos; Terman, Jonathan R.; González-Billault, Christian; Ahmed, Giasuddin

2016-01-01

Actin and its ability to polymerize into dynamic filaments is critical for the form and function of cells throughout the body. While multiple proteins have been characterized as affecting actin dynamics through non-covalent means, actin and its protein regulators are also susceptible to covalent modifications of their amino acid residues. In this regard, oxidation-reduction (Redox) intermediates have emerged as key modulators of the actin cytoskeleton with multiple different effects on cellular form and function. Here, we review work implicating Redox intermediates in post-translationally altering actin and discuss what is known regarding how these alterations affect the properties of actin. We also focus on two of the best characterized enzymatic sources of these Redox intermediates – the NADPH oxidase NOX and the flavoprotein monooxygenase MICAL – and detail how they have both been identified as altering actin, but share little similarity and employ different means to regulate actin dynamics. Finally, we discuss the role of these enzymes and redox signaling in regulating the actin cytoskeleton in vivo and highlight their importance for neuronal form and function in health and disease. PMID:27309342

Runaway Train: A Leaky Radiosensitive SCID with Skin Lesions and Multiple Lymphomas.

PubMed

Fevang, Børre; Fagerli, Unn Merete; Sorte, Hanne; Aarset, Harald; Hov, Håkon; Langmyr, Marit; Keil, Thomas Morten; Bjørge, Ellen; Aukrust, Pål; Stray-Pedersen, Asbjørg; Gedde-Dahl, Tobias

2018-01-01

The nuclease Artemis is essential for the development of T-cell and B-cell receptors and repair of DNA double-strand breaks, and a loss of expression or function will lead to a radiosensitive severe combined immunodeficiency with no functional T-cells or B-cells (T-B-SCID). Hypomorphic mutations in the Artemis gene can lead to a functional, but reduced, T-cell and B-cell repertoire with a more indolent clinical course called "leaky" SCID. Here, we present the case of a young man who had increasingly aggressive lymphoproliferative skin lesions from 2 years of age which developed into multiple EBV+ B-cell lymphomas, where a hypomorphic mutation in the Artemis gene was found in a diagnostic race against time using whole exome sequencing. The patient was given a haploidentical stem cell transplant while in remission for his lymphomas and although the initial course was successful, he succumbed to a serious Pneumocystis jirovecii pneumonia 5 months after the transplant. The case underscores the importance of next-generation sequencing in the diagnosis of patients with suspected severe immunodeficiency.

Theoretical constraints in the design of multivariable control systems

NASA Technical Reports Server (NTRS)

Rynaski, E. G.; Mook, D. Joseph; Depena, Juan

1991-01-01

The research being performed under NASA Grant NAG1-1361 involves a more clear understanding and definition of the constraints involved in the pole-zero placement or assignment process for multiple input, multiple output systems. Complete state feedback to more than a single controller under conditions of complete controllability and observability is redundant if pole placement alone is the design objective. The additional feedback gains, above and beyond those required for pole placement can be used for eignevalue assignment or zero placement of individual closed loop transfer functions. Because both poles and zeros of individual closed loop transfer functions strongly affect the dynamic response to a pilot command input, the pole-zero placement problem is important. When fewer controllers than degrees of freedom of motion are available, complete design freedom is not possible, the transmission zeros constrain the regions of possible pole-zero placement. The effect of transmission zero constraints on the design possibilities, selection of transmission zeros and the avoidance of producing non-minimum phase transfer functions is the subject of the research being performed under this grant.

QualiCOP: real-world effectiveness, tolerability, and quality of life in patients with relapsing-remitting multiple sclerosis treated with glatiramer acetate, treatment-naïve patients, and previously treated patients.

PubMed

Ziemssen, Tjalf; Calabrese, Pasquale; Penner, Iris-Katharina; Apfel, Rainer

2016-04-01

Treatment of symptoms and signs beyond the expanded disability status scale remains a major target in multiple sclerosis. QualiCOP was an observational, non-interventional, open-label study conducted at 170 sites in Germany. Of the 754 enrolled patients, 96 % had relapsing-remitting multiple sclerosis (MS) and were either disease-modifying therapy naïve (de novo, n = 481) or previously treated (n = 237) with once-daily, subcutaneous 20-mg/mL glatiramer acetate (GA). Assessments of relapse rate, disease progression, overall functioning, quality of life (QoL), cognition, fatigue, and depression were performed over 24 months. GA treatment over 24 months was associated with reduced annual relapse rate for previously treated (from 0.98 to 0.54 relapses) and de novo (from 0.81 to 0.48 relapses) patients. Multiple Sclerosis Functional Composite scores showed slight improvement in both cohorts (all p < 0.01). Paced Auditory Serial Addition Test and Multiple Sclerosis Inventory Cognition scale scores showed robust improvement in cognition among previously treated and de novo cohorts (all p < 0.001). General Depression Scale scores showed significantly reduced depressive symptoms (p < 0.001). Disease severity, fatigue, and QoL were stable over the observational period. These real-world findings suggest that patients with MS show benefit from GA treatment in important QoL parameters beyond standard measures of relapse and disease severity.

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

Locally rare species influence grassland ecosystem multifunctionality

PubMed Central

Manning, Peter; Prati, Daniel; Gossner, Martin M.; Alt, Fabian; Arndt, Hartmut; Baumgartner, Vanessa; Binkenstein, Julia; Birkhofer, Klaus; Blaser, Stefan; Blüthgen, Nico; Boch, Steffen; Böhm, Stefan; Börschig, Carmen; Buscot, Francois; Diekötter, Tim; Heinze, Johannes; Hölzel, Norbert; Jung, Kirsten; Klaus, Valentin H.; Klein, Alexandra-Maria; Kleinebecker, Till; Klemmer, Sandra; Krauss, Jochen; Lange, Markus; Morris, E. Kathryn; Müller, Jörg; Oelmann, Yvonne; Overmann, Jörg; Pašalić, Esther; Renner, Swen C.; Rillig, Matthias C.; Schaefer, H. Martin; Schloter, Michael; Schmitt, Barbara; Schöning, Ingo; Schrumpf, Marion; Sikorski, Johannes; Socher, Stephanie A.; Solly, Emily F.; Sonnemann, Ilja; Sorkau, Elisabeth; Steckel, Juliane; Steffan-Dewenter, Ingolf; Stempfhuber, Barbara; Tschapka, Marco; Türke, Manfred; Venter, Paul; Weiner, Christiane N.; Weisser, Wolfgang W.; Werner, Michael; Westphal, Catrin; Wilcke, Wolfgang; Wolters, Volkmar; Wubet, Tesfaye; Wurst, Susanne; Fischer, Markus; Allan, Eric

2016-01-01

Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity–multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities. PMID:27114572

Locally rare species influence grassland ecosystem multifunctionality.

PubMed

Soliveres, Santiago; Manning, Peter; Prati, Daniel; Gossner, Martin M; Alt, Fabian; Arndt, Hartmut; Baumgartner, Vanessa; Binkenstein, Julia; Birkhofer, Klaus; Blaser, Stefan; Blüthgen, Nico; Boch, Steffen; Böhm, Stefan; Börschig, Carmen; Buscot, Francois; Diekötter, Tim; Heinze, Johannes; Hölzel, Norbert; Jung, Kirsten; Klaus, Valentin H; Klein, Alexandra-Maria; Kleinebecker, Till; Klemmer, Sandra; Krauss, Jochen; Lange, Markus; Morris, E Kathryn; Müller, Jörg; Oelmann, Yvonne; Overmann, Jörg; Pašalić, Esther; Renner, Swen C; Rillig, Matthias C; Schaefer, H Martin; Schloter, Michael; Schmitt, Barbara; Schöning, Ingo; Schrumpf, Marion; Sikorski, Johannes; Socher, Stephanie A; Solly, Emily F; Sonnemann, Ilja; Sorkau, Elisabeth; Steckel, Juliane; Steffan-Dewenter, Ingolf; Stempfhuber, Barbara; Tschapka, Marco; Türke, Manfred; Venter, Paul; Weiner, Christiane N; Weisser, Wolfgang W; Werner, Michael; Westphal, Catrin; Wilcke, Wolfgang; Wolters, Volkmar; Wubet, Tesfaye; Wurst, Susanne; Fischer, Markus; Allan, Eric

2016-05-19

Species diversity promotes the delivery of multiple ecosystem functions (multifunctionality). However, the relative functional importance of rare and common species in driving the biodiversity-multifunctionality relationship remains unknown. We studied the relationship between the diversity of rare and common species (according to their local abundances and across nine different trophic groups), and multifunctionality indices derived from 14 ecosystem functions on 150 grasslands across a land-use intensity (LUI) gradient. The diversity of above- and below-ground rare species had opposite effects, with rare above-ground species being associated with high levels of multifunctionality, probably because their effects on different functions did not trade off against each other. Conversely, common species were only related to average, not high, levels of multifunctionality, and their functional effects declined with LUI. Apart from the community-level effects of diversity, we found significant positive associations between the abundance of individual species and multifunctionality in 6% of the species tested. Species-specific functional effects were best predicted by their response to LUI: species that declined in abundance with land use intensification were those associated with higher levels of multifunctionality. Our results highlight the importance of rare species for ecosystem multifunctionality and help guiding future conservation priorities. © 2016 The Author(s).

The relationship between spatial configuration and functional connectivity of brain regions

PubMed Central

Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C

2018-01-01

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used ‘functional connectivity fingerprints’ to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. PMID:29451491

Visual impairment, but not hearing impairment, is independently associated with lower subjective well-being among individuals over 95 years of age: A population-based study.

PubMed

Liu, Zuyun; Wu, Di; Huang, Jiapin; Qian, Degui; Chen, Fei; Xu, Jun; Li, Shilin; Jin, Li; Wang, Xiaofeng

2016-01-01

Sensory impairment affects an increasing number of elderly adults, with a negative psychological impact. Our objective was to examine the associations of visual and hearing impairment with subjective well-being (SWB), an important psychological concept defined by life satisfaction [LS], positive affect [PA], negative affect [NA], and affect balance [AB] among long-lived individuals (LLIs) over 95 years of age. Data on 442 LLIs from the Rugao longevity cohort, a population-based study in Rugao, China, were analyzed. Graded classifications of visual and hearing impairment (none, mild, moderate, and severe) were constructed from self-reported items. Bivariate correlation and multiple regression analysis were performed to test the associations. Approximately 66.1% and 87.3% of the subjects reported varying degrees of visual and hearing impairment. Following the degree of vision impairment, LS, PA, and AB decreased linearly, whereas NA increased linearly (all p for trend<0.05). Vision was significantly related to LS (r=0.238, p<0.001), PA (r=0.142, p<0.01), NA (r=-0.157, p<0.001), and AB (r=0.206, p<0.001). After adjustment for multiple variables including functional ability, an important factor of SWB, the associations of vision impairment with LS, NA, and AB, while diminished, still existed. Visual impairment, but not hearing impairment, was independently associated with low SWB among LLIs, and functional ability may play a mediating role in the observed relationship. The findings indicate that rehabilitation targeted for those with reduced vision and functioning in long-lived populations may be important for promoting well-being and quality of life. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[Quality of life after multiple trauma].

PubMed

Mörsdorf, P; Becker, S C; Holstein, J H; Burkhardt, M; Pohlemann, T

2014-03-01

Multiple trauma is an independent injury pattern which, because of its complexity, is responsible for 25 % of the costs for the treatment of all injured patients. Because of the often long-lasting physical impairment and the high incidence of residual permanent handicaps, it is apparent that multiple trauma can lead to a reduction in patient quality of life. The aim of this study was to give an overview of the known data concerning the change in quality of life for multiple trauma patients. Furthermore, predictors for the reduction of quality of life after multiple trauma will be identified. A MedLine search was performed to identify studies dealing with the outcome after multiple trauma. In addition to functional outcome parameters, the term quality of life has become more important in recent years when it comes to evaluating the outcome following injury. While the mortality after multiple trauma could be significantly reduced over the years, there is no comparable effect on the quality of life. Predictors for a worse quality of life after multiple trauma are female gender, high age, low social status, concomitant head injuries and injury to the lower extremities. The fact that mortality after multiple trauma has decreased but not impairment of the quality of life makes it clear that in addition to the acute medical treatment, a follow-up treatment including not only physiotherapy but also psychotherapy is crucial for multiple trauma patients.

Hypoxia and Mucosal Inflammation

PubMed Central

Colgan, Sean P.; Campbell, Eric L.; Kominsky, Douglas J.

2016-01-01

Sites of inflammation are defined by significant changes in metabolic activity. Recent studies have suggested that O2 metabolism and hypoxia play a prominent role in inflammation so-called “inflammatory hypoxia,” which results from a combination of recruited inflammatory cells (e.g., neutrophils and monocytes), the local proliferation of multiple cell types, and the activation of multiple O2-consuming enzymes during inflammation. These shifts in energy supply and demand result in localized regions of hypoxia and have revealed the important function off the transcription factor HIF (hypoxia-inducible factor) in the regulation of key target genes that promote inflammatory resolution. Analysis of these pathways has provided multiple opportunities for understanding basic mechanisms of inflammation and has defined new targets for intervention. Here, we review recent work addressing tissue hypoxia and metabolic control of inflammation and immunity. PMID:27193451

Importance of dual delivery systems for bone tissue engineering.

PubMed

Farokhi, Mehdi; Mottaghitalab, Fatemeh; Shokrgozar, Mohammad Ali; Ou, Keng-Liang; Mao, Chuanbin; Hosseinkhani, Hossein

2016-03-10

Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering. Copyright © 2015 Elsevier B.V. All rights reserved.

Exploration of Multi-State Conformational Dynamics and Underlying Global Functional Landscape of Maltose Binding Protein

PubMed Central

Wang, Yong; Tang, Chun; Wang, Erkang; Wang, Jin

2012-01-01

An increasing number of biological machines have been revealed to have more than two macroscopic states. Quantifying the underlying multiple-basin functional landscape is essential for understanding their functions. However, the present models seem to be insufficient to describe such multiple-state systems. To meet this challenge, we have developed a coarse grained triple-basin structure-based model with implicit ligand. Based on our model, the constructed functional landscape is sufficiently sampled by the brute-force molecular dynamics simulation. We explored maltose-binding protein (MBP) which undergoes large-scale domain motion between open, apo-closed (partially closed) and holo-closed (fully closed) states responding to ligand binding. We revealed an underlying mechanism whereby major induced fit and minor population shift pathways co-exist by quantitative flux analysis. We found that the hinge regions play an important role in the functional dynamics as well as that increases in its flexibility promote population shifts. This finding provides a theoretical explanation of the mechanistic discrepancies in PBP protein family. We also found a functional “backtracking” behavior that favors conformational change. We further explored the underlying folding landscape in response to ligand binding. Consistent with earlier experimental findings, the presence of ligand increases the cooperativity and stability of MBP. This work provides the first study to explore the folding dynamics and functional dynamics under the same theoretical framework using our triple-basin functional model. PMID:22532792

Bacterial chemoreceptors: high-performance signaling in networked arrays.

PubMed

Hazelbauer, Gerald L; Falke, Joseph J; Parkinson, John S

2008-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on-off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device.

Toward a multiscale modeling framework for understanding serotonergic function

PubMed Central

Wong-Lin, KongFatt; Wang, Da-Hui; Moustafa, Ahmed A; Cohen, Jeremiah Y; Nakamura, Kae

2017-01-01

Despite its importance in regulating emotion and mental wellbeing, the complex structure and function of the serotonergic system present formidable challenges toward understanding its mechanisms. In this paper, we review studies investigating the interactions between serotonergic and related brain systems and their behavior at multiple scales, with a focus on biologically-based computational modeling. We first discuss serotonergic intracellular signaling and neuronal excitability, followed by neuronal circuit and systems levels. At each level of organization, we will discuss the experimental work accompanied by related computational modeling work. We then suggest that a multiscale modeling approach that integrates the various levels of neurobiological organization could potentially transform the way we understand the complex functions associated with serotonin. PMID:28417684

Bacterial chemoreceptors: high-performance signaling in networked arrays

PubMed Central

Hazelbauer, Gerald L.; Falke, Joseph J.; Parkinson, John S.

2010-01-01

Chemoreceptors are crucial components in the bacterial sensory systems that mediate chemotaxis. Chemotactic responses exhibit exquisite sensitivity, extensive dynamic range and precise adaptation. The mechanisms that mediate these high-performance functions involve not only actions of individual proteins but also interactions among clusters of components, localized in extensive patches of thousands of molecules. Recently, these patches have been imaged in native cells, important features of chemoreceptor structure and on–off switching have been identified, and new insights have been gained into the structural basis and functional consequences of higher order interactions among sensory components. These new data suggest multiple levels of molecular interactions, each of which contribute specific functional features and together create a sophisticated signaling device. PMID:18165013

Working Memory in Children With Neurocognitive Effects From Sickle Cell Disease: Contributions of the Central Executive and Processing Speed

PubMed Central

Smith, Kelsey E.; Schatz, Jeffrey

2017-01-01

Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children with SCD and 85 matched comparison children using Baddeley’s working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD. PMID:27759435

Integrating multiple fitting regression and Bayes decision for cancer diagnosis with transcriptomic data from tumor-educated blood platelets.

PubMed

Huang, Guangzao; Yuan, Mingshun; Chen, Moliang; Li, Lei; You, Wenjie; Li, Hanjie; Cai, James J; Ji, Guoli

2017-10-07

The application of machine learning in cancer diagnostics has shown great promise and is of importance in clinic settings. Here we consider applying machine learning methods to transcriptomic data derived from tumor-educated platelets (TEPs) from individuals with different types of cancer. We aim to define a reliability measure for diagnostic purposes to increase the potential for facilitating personalized treatments. To this end, we present a novel classification method called MFRB (for Multiple Fitting Regression and Bayes decision), which integrates the process of multiple fitting regression (MFR) with Bayes decision theory. MFR is first used to map multidimensional features of the transcriptomic data into a one-dimensional feature. The probability density function of each class in the mapped space is then adjusted using the Gaussian probability density function. Finally, the Bayes decision theory is used to build a probabilistic classifier with the estimated probability density functions. The output of MFRB can be used to determine which class a sample belongs to, as well as to assign a reliability measure for a given class. The classical support vector machine (SVM) and probabilistic SVM (PSVM) are used to evaluate the performance of the proposed method with simulated and real TEP datasets. Our results indicate that the proposed MFRB method achieves the best performance compared to SVM and PSVM, mainly due to its strong generalization ability for limited, imbalanced, and noisy data.

Modulatory mechanisms and multiple functions of somatodendritic A-type K+ channel auxiliary subunits

PubMed Central

Jerng, Henry H.; Pfaffinger, Paul J.

2014-01-01

Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming α-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (ISA) channel based on Kv4 α-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPLPs). KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1) the molecular mechanism underlying the unique properties of different N-terminal variants, (2) the shaping of native ISA properties by the concerted actions of KChIPs and DPLP variants, and (3) the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders. PMID:24723849

Modulatory mechanisms and multiple functions of somatodendritic A-type K (+) channel auxiliary subunits.

PubMed

Jerng, Henry H; Pfaffinger, Paul J

2014-01-01

Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming α-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (ISA) channel based on Kv4 α-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPLPs). KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1) the molecular mechanism underlying the unique properties of different N-terminal variants, (2) the shaping of native ISA properties by the concerted actions of KChIPs and DPLP variants, and (3) the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders.

Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

PubMed Central

Essex, Marilyn J.; Shirtcliff, Elizabeth A.; Burk, Linnea R.; Ruttle, Paula L.; Klein, Marjorie H.; Slattery, Marcia J.; Kalin, Ned H.; Armstrong, Jeffrey M.

2012-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children’s HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (trait-like and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A 3-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its co-variation with mental health symptoms. ELS influenced trait-like cortisol level and slope, with both hyper- and hypo-arousal evident depending on type of ELS. Further, type(s) of ELS influenced co-variation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence. PMID:22018080

Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: a study of the allostatic process from childhood into adolescence.

PubMed

Essex, Marilyn J; Shirtcliff, Elizabeth A; Burk, Linnea R; Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M

2011-11-01

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

Decision tree analysis in subarachnoid hemorrhage: prediction of outcome parameters during the course of aneurysmal subarachnoid hemorrhage using decision tree analysis.

PubMed

Hostettler, Isabel Charlotte; Muroi, Carl; Richter, Johannes Konstantin; Schmid, Josef; Neidert, Marian Christoph; Seule, Martin; Boss, Oliver; Pangalu, Athina; Germans, Menno Robbert; Keller, Emanuela

2018-01-19

OBJECTIVE The aim of this study was to create prediction models for outcome parameters by decision tree analysis based on clinical and laboratory data in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS The database consisted of clinical and laboratory parameters of 548 patients with aSAH who were admitted to the Neurocritical Care Unit, University Hospital Zurich. To examine the model performance, the cohort was randomly divided into a derivation cohort (60% [n = 329]; training data set) and a validation cohort (40% [n = 219]; test data set). The classification and regression tree prediction algorithm was applied to predict death, functional outcome, and ventriculoperitoneal (VP) shunt dependency. Chi-square automatic interaction detection was applied to predict delayed cerebral infarction on days 1, 3, and 7. RESULTS The overall mortality was 18.4%. The accuracy of the decision tree models was good for survival on day 1 and favorable functional outcome at all time points, with a difference between the training and test data sets of < 5%. Prediction accuracy for survival on day 1 was 75.2%. The most important differentiating factor was the interleukin-6 (IL-6) level on day 1. Favorable functional outcome, defined as Glasgow Outcome Scale scores of 4 and 5, was observed in 68.6% of patients. Favorable functional outcome at all time points had a prediction accuracy of 71.1% in the training data set, with procalcitonin on day 1 being the most important differentiating factor at all time points. A total of 148 patients (27%) developed VP shunt dependency. The most important differentiating factor was hyperglycemia on admission. CONCLUSIONS The multiple variable analysis capability of decision trees enables exploration of dependent variables in the context of multiple changing influences over the course of an illness. The decision tree currently generated increases awareness of the early systemic stress response, which is seemingly pertinent for prognostication.

The evolvability of programmable hardware.

PubMed

Raman, Karthik; Wagner, Andreas

2011-02-06

In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected 'neutral networks' in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 10(45) logic circuits ('genotypes') and 10(19) logic functions ('phenotypes'). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry.

The evolvability of programmable hardware

PubMed Central

Raman, Karthik; Wagner, Andreas

2011-01-01

In biological systems, individual phenotypes are typically adopted by multiple genotypes. Examples include protein structure phenotypes, where each structure can be adopted by a myriad individual amino acid sequence genotypes. These genotypes form vast connected ‘neutral networks’ in genotype space. The size of such neutral networks endows biological systems not only with robustness to genetic change, but also with the ability to evolve a vast number of novel phenotypes that occur near any one neutral network. Whether technological systems can be designed to have similar properties is poorly understood. Here we ask this question for a class of programmable electronic circuits that compute digital logic functions. The functional flexibility of such circuits is important in many applications, including applications of evolutionary principles to circuit design. The functions they compute are at the heart of all digital computation. We explore a vast space of 1045 logic circuits (‘genotypes’) and 1019 logic functions (‘phenotypes’). We demonstrate that circuits that compute the same logic function are connected in large neutral networks that span circuit space. Their robustness or fault-tolerance varies very widely. The vicinity of each neutral network contains circuits with a broad range of novel functions. Two circuits computing different functions can usually be converted into one another via few changes in their architecture. These observations show that properties important for the evolvability of biological systems exist in a commercially important class of electronic circuitry. They also point to generic ways to generate fault-tolerant, adaptable and evolvable electronic circuitry. PMID:20534598

Architecture for Multiple Interacting Robot Intelligences

NASA Technical Reports Server (NTRS)

Peters, Richard Alan, II (Inventor)

2008-01-01

An architecture for robot intelligence enables a robot to learn new behaviors and create new behavior sequences autonomously and interact with a dynamically changing environment. Sensory information is mapped onto a Sensory Ego-Sphere (SES) that rapidly identifies important changes in the environment and functions much like short term memory. Behaviors are stored in a database associative memory (DBAM) that creates an active map from the robot's current state to a goal state and functions much like long term memory. A dream state converts recent activities stored in the SES and creates or modifies behaviors in the DBAM.

[Long non-coding RNAs in plants].

PubMed

Xiaoqing, Huang; Dandan, Li; Juan, Wu

2015-04-01

Long non-coding RNAs (lncRNAs), which are longer than 200 nucleotides in length, widely exist in organisms and function in a variety of biological processes. Currently, most of lncRNAs found in plants are transcribed by RNA polymerase Ⅱ and mediate gene expression through multiple mechanisms, such as target mimicry, transcription interference, histone methylation and DNA methylation, and play important roles in flowering, male sterility, nutrition metabolism, biotic and abiotic stress and other biological processes as regulators in plants. In this review, we summarize the databases, prediction methods, and possible functions of plant lncRNAs discovered in recent years.

Diagnosis of NMOS DRAM functional performance as affected by a picosecond dye laser

NASA Technical Reports Server (NTRS)

Kim, Q.; Schwartz, H. R.; Edmonds, L. D.; Zoutendyk, J. A.

1992-01-01

A picosec pulsed dye laser beam was at selected wavelengths successfully used to simulate heavy-ion single-event effects (SEEs) in negative channel NMOS DRAMs. A DRAM was used to develop the test technique because bit-mapping capability and previous heavy-ion upset data were available. The present analysis is the first to establish such a correlation between laser and heavy-ion data for devices, such as the NMOS DRAM, where charge collection is dominated by long-range diffusion, which is controlled by carrier density at remote distances from a depletion region. In the latter case, penetration depth is an important parameter and is included in the present analysis. A single-pulse picosecond dye laser beam (1.5 microns diameter) focused onto a single cell component can upset a single memory cell; clusters of memory cell upsets (multiple errors) were observed when the laser energy was increased above the threshold energy. The multiple errors were analyzed as a function of the bias voltage and total energy of a single pulse. A diffusion model to distinguish the multiple upsets from the laser-induced charge agreed well with previously reported heavy ion data.

Oxygen Vacancy-Tuned Physical Properties in Perovskite Thin Films with Multiple B-site Valance States

DOE PAGES

Enriquez, Erik; Chen, Aiping; Harrell, Zach; ...

2017-04-18

Controlling oxygen content in perovskite oxides with ABO 3 structure is one of most critical steps for tuning their functionality. Notably, there have been tremendous efforts to understand the effect of changes in oxygen content on the properties of perovskite thin films that are not composed of cations with multiple valance states. Here, we study the effect of oxygen vacancies on structural and electrical properties in epitaxial thin films of SrFeO 3-δ (SFO), where SFO is a compound with multiple valance states at the B site. Various annealing treatments are used to produce different oxygen contents in the films, whichmore » has resulted in significant structural changes in the fully strained SFO films. The out-of-plane lattice parameter and tetragonality increase with decreasing oxygen concentration, indicating the crystal structure is closely related to the oxygen content. Importantly, variation of the oxygen content in the films significantly affects the dielectric properties, leakage conduction mechanisms, and the resistive hysteresis of the materials. These results establish the relationship between oxygen content and structural and functional properties for a range of multivalent transition metal oxides.« less

Oxygen Vacancy-Tuned Physical Properties in Perovskite Thin Films with Multiple B-site Valance States

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

Enriquez, Erik; Chen, Aiping; Harrell, Zach

Controlling oxygen content in perovskite oxides with ABO 3 structure is one of most critical steps for tuning their functionality. Notably, there have been tremendous efforts to understand the effect of changes in oxygen content on the properties of perovskite thin films that are not composed of cations with multiple valance states. Here, we study the effect of oxygen vacancies on structural and electrical properties in epitaxial thin films of SrFeO 3-δ (SFO), where SFO is a compound with multiple valance states at the B site. Various annealing treatments are used to produce different oxygen contents in the films, whichmore » has resulted in significant structural changes in the fully strained SFO films. The out-of-plane lattice parameter and tetragonality increase with decreasing oxygen concentration, indicating the crystal structure is closely related to the oxygen content. Importantly, variation of the oxygen content in the films significantly affects the dielectric properties, leakage conduction mechanisms, and the resistive hysteresis of the materials. These results establish the relationship between oxygen content and structural and functional properties for a range of multivalent transition metal oxides.« less

The clinico-radiological paradox of cognitive function and MRI burden of white matter lesions in people with multiple sclerosis: A systematic review and meta-analysis.

PubMed

Mollison, Daisy; Sellar, Robin; Bastin, Mark; Mollison, Denis; Chandran, Siddharthan; Wardlaw, Joanna; Connick, Peter

2017-01-01

Moderate correlation exists between the imaging quantification of brain white matter lesions and cognitive performance in people with multiple sclerosis (MS). This may reflect the greater importance of other features, including subvisible pathology, or methodological limitations of the primary literature. To summarise the cognitive clinico-radiological paradox and explore the potential methodological factors that could influence the assessment of this relationship. Systematic review and meta-analysis of primary research relating cognitive function to white matter lesion burden. Fifty papers met eligibility criteria for review, and meta-analysis of overall results was possible in thirty-two (2050 participants). Aggregate correlation between cognition and T2 lesion burden was r = -0.30 (95% confidence interval: -0.34, -0.26). Wide methodological variability was seen, particularly related to key factors in the cognitive data capture and image analysis techniques. Resolving the persistent clinico-radiological paradox will likely require simultaneous evaluation of multiple components of the complex pathology using optimum measurement techniques for both cognitive and MRI feature quantification. We recommend a consensus initiative to support common standards for image analysis in MS, enabling benchmarking while also supporting ongoing innovation.

Dementia: A complex disease with multiple etiologies and multiple treatments.

PubMed

Fisher, Travis J; Schwartz, Ann C; Greenspan, Heather N; Heinrich, Thomas W

As the population of the United States ages, the rates of dementia are also likely to increase. Clinicians will, therefore, likely be asked to evaluate and treat an escalating number of patients experiencing a decline in multiple domains of cognitive function, which is the hallmark of neurocognitive disorders. It is also probable that clinicians will be confronted with management dilemmas related to the myriad of psychological and behavioral problems that often occur as a consequence of the neurocognitive impairment. In fact, these behavioral and psychological issues might be the initial symptoms that lead the patient to present to the clinician. Dementia has multiple potential etiologies, and a careful diagnostic assessment is imperative to best characterize the specific type of dementia impacting the patient. This is important, as knowing the type of dementia helps the clinician choose the most effective treatment. Potential treatments should be interdisciplinary in scope, patient/family-centered, and may include both nonpharmacologic and pharmacologic treatments. © The Author(s) 2016.

A study of the Interaction of bovine Hemoglobin with Synthetic dyes using Spectroscopic techniques and Molecular docking

NASA Astrophysics Data System (ADS)

Kamaljeet; Bansal, Saurabh; SenGupta, Uttara

2016-12-01

Synthetic dyes are a very efficient class of dyes that are ingested or come into contact with the skin from numerous sources (cosmetics, textiles, leather, paper, drugs). An important component of their safety profile is the interactions that they form after they enter the body. Hemoglobin is a functionally important protein that can form multiple interactions with soluble compounds present in the blood, and hence forms an important aspect of the toxicological or safety profile of the dyes. Here we study the interaction between bovine haemoglobin and organic dyes using UV-Vis absorbance and fluorescence spectroscopy. Molecular modelling was used to visualise the binding site and partners of the dye molecules, within the hemoglobin molecule. We find that all four dyes studied form sufficiently strong interactions with haemoglobin to allow for the formation of potentially toxic interactions. Molecular modelling showed that all 4 dyes bound within the central cavity of the haemoglobin molecule. However, binding partners could not be identified as multiple binding conformations with very similar energies were possible for each dye.

A Study of the Interaction of Bovine Hemoglobin with Synthetic Dyes Using Spectroscopic Techniques and Molecular Docking.

PubMed

Kamaljeet; Bansal, Saurabh; SenGupta, Uttara

2016-01-01

Synthetic dyes are a very efficient class of dyes that are ingested or come into contact with the skin from numerous sources (cosmetics, textiles, leather, paper, and drugs). An important component of their safety profile is the interactions that they form after they enter the body. Hemoglobin is a functionally important protein that can form multiple interactions with soluble compounds present in the blood, and hence forms an important aspect of the toxicological or safety profile of the dyes. Here we study the interaction between bovine hemoglobin and organic dyes using UV-Vis absorbance and fluorescence spectroscopy. Molecular modeling was used to visualize the binding site and partners of the dye molecules, within the hemoglobin molecule. We find that all four dyes studied form sufficiently strong interactions with hemoglobin to allow for the formation of potentially toxic interactions. Molecular modeling showed that all four dyes bind within the central cavity of the hemoglobin molecule. However, binding partners could not be identified as multiple binding conformations with very similar energies were possible for each dye.

Addressing Chronic Malnutrition through Multi-Sectoral, Sustainable Approaches: A Review of the Causes and Consequences

PubMed Central

Reinhardt, Kristina; Fanzo, Jessica

2014-01-01

Chronic malnutrition, including stunting, is an important example of a global challenge that spans multiple sectors, specifically health, agriculture, and the environment. The objective of this paper is to review current knowledge on the causes and consequences of chronic malnutrition and their relationship with multiple sectors. Understanding the causes includes approaching chronic malnutrition from the basic, underlying, and immediate levels. The causes reach from macro-level environmental influences to specific micronutrient intake. In order to effectively address stunting, it is important to understand the timing of stunting and the ability of individuals to catch up in terms of linear growth, cognitive ability, and immune function. The consequences of chronic malnutrition are transgenerational and they have an impact at the individual, community, and national level in the short- and long-term. There are still many gaps in knowledge regarding both the causes and consequences of chronic malnutrition, particularly when it comes to the interaction with agriculture and the environment, and understanding these gaps is important to addressing the burden of chronic malnutrition through evidence-based interventions. PMID:25988116

Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) Reveals Multiple Protease-Like Transcripts.

PubMed

Valencia, Arnubio; Wang, Haichuan; Soto, Alberto; Aristizabal, Manuel; Arboleda, Jorge W; Eyun, Seong-Il; Noriega, Daniel D; Siegfried, Blair

2016-01-01

The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest.

Pyrosequencing the Midgut Transcriptome of the Banana Weevil Cosmopolites sordidus (Germar) (Coleoptera: Curculionidae) Reveals Multiple Protease-Like Transcripts

PubMed Central

Valencia, Arnubio; Wang, Haichuan; Soto, Alberto; Aristizabal, Manuel; Arboleda, Jorge W.; Eyun, Seong-il; Noriega, Daniel D.; Siegfried, Blair

2016-01-01

The banana weevil Cosmopolites sordidus is an important and serious insect pest in most banana and plantain-growing areas of the world. In spite of the economic importance of this insect pest very little genomic and transcriptomic information exists for this species. In the present study, we characterized the midgut transcriptome of C. sordidus using massive 454-pyrosequencing. We generated over 590,000 sequencing reads that assembled into 30,840 contigs with more than 400 bp, representing a significant expansion of existing sequences available for this insect pest. Among them, 16,427 contigs contained one or more GO terms. In addition, 15,263 contigs were assigned an EC number. In-depth transcriptome analysis identified genes potentially involved in insecticide resistance, peritrophic membrane biosynthesis, immunity-related function and defense against pathogens, and Bacillus thuringiensis toxins binding proteins as well as multiple enzymes involved with protein digestion. This transcriptome will provide a valuable resource for understanding larval physiology and for identifying novel target sites and management approaches for this important insect pest. PMID:26949943

Multiple Functional Domains of Enterococcus faecalis Aggregation Substance Asc10 Contribute to Endocarditis Virulence ▿ †

PubMed Central

Chuang, Olivia N.; Schlievert, Patrick M.; Wells, Carol L.; Manias, Dawn A.; Tripp, Timothy J.; Dunny, Gary M.

2009-01-01

Aggregation substance proteins encoded by sex pheromone plasmids increase the virulence of Enterococcus faecalis in experimental pathogenesis models, including infectious endocarditis models. These large surface proteins may contain multiple functional domains involved in various interactions with other bacterial cells and with the mammalian host. Aggregation substance Asc10, encoded by plasmid pCF10, is induced during growth in the mammalian bloodstream, and pCF10 carriage gives E. faecalis a significant selective advantage in this environment. We employed a rabbit model to investigate the role of various functional domains of Asc10 in endocarditis. The data suggested that the bacterial load of the infected tissue was the best indicator of virulence. Isogenic strains carrying either no plasmid, wild-type pCF10, a pCF10 derivative with an in-frame deletion of the prgB gene encoding Asc10, or pCF10 derivatives expressing other alleles of prgB were examined in this model. Previously identified aggregation domains contributed to the virulence associated with the wild-type protein, and a strain expressing an Asc10 derivative in which glycine residues in two RGD motifs were changed to alanine residues showed the greatest reduction in virulence. Remarkably, this strain and the strain carrying the pCF10 derivative with the in-frame deletion of prgB were both significantly less virulent than an isogenic plasmid-free strain. The data demonstrate that multiple functional domains are important in Asc10-mediated interactions with the host during the course of experimental endocarditis and that in the absence of a functional prgB gene, pCF10 carriage is actually disadvantageous in vivo. PMID:18955479

Emergence of Functional Hierarchy in a Multiple Timescale Neural Network Model: A Humanoid Robot Experiment

PubMed Central

Yamashita, Yuichi; Tani, Jun

2008-01-01

It is generally thought that skilled behavior in human beings results from a functional hierarchy of the motor control system, within which reusable motor primitives are flexibly integrated into various sensori-motor sequence patterns. The underlying neural mechanisms governing the way in which continuous sensori-motor flows are segmented into primitives and the way in which series of primitives are integrated into various behavior sequences have, however, not yet been clarified. In earlier studies, this functional hierarchy has been realized through the use of explicit hierarchical structure, with local modules representing motor primitives in the lower level and a higher module representing sequences of primitives switched via additional mechanisms such as gate-selecting. When sequences contain similarities and overlap, however, a conflict arises in such earlier models between generalization and segmentation, induced by this separated modular structure. To address this issue, we propose a different type of neural network model. The current model neither makes use of separate local modules to represent primitives nor introduces explicit hierarchical structure. Rather than forcing architectural hierarchy onto the system, functional hierarchy emerges through a form of self-organization that is based on two distinct types of neurons, each with different time properties (“multiple timescales”). Through the introduction of multiple timescales, continuous sequences of behavior are segmented into reusable primitives, and the primitives, in turn, are flexibly integrated into novel sequences. In experiments, the proposed network model, coordinating the physical body of a humanoid robot through high-dimensional sensori-motor control, also successfully situated itself within a physical environment. Our results suggest that it is not only the spatial connections between neurons but also the timescales of neural activity that act as important mechanisms leading to functional hierarchy in neural systems. PMID:18989398

The importance of considering differential item functioning in investigating the impact of chronic conditions on health-related quality of life in a multi-ethnic Asian population.

PubMed

Abdin, Edimansyah; Subramaniam, Mythily; Picco, Louisa; Pang, Shirlene; Vaingankar, Janhavi Ajit; Shahwan, Shazana; Sagayadevan, Vathsala; Zhang, Yunjue; Chong, Siow Ann

2017-04-01

The present study aims to examine the impact of chronic conditions after adjusting for differential item functioning (DIF) on the various aspects of health-related quality of life (HRQoL) in a multi-ethnic Asian population in Singapore. Data on 3006 participants from a nation-wide cross-sectional survey of mental health literacy conducted in Singapore were used. Multiple Indicators Multiple Causes model was used to investigate the effects of chronic medical conditions on various HRQoL dimensions assessed with the 36-item Medical Outcomes Study Short Form Health Survey (SF-36) after adjusting for DIF. Twenty out of 36 items were detected with DIF for chronic conditions including high blood pressure, cardiovascular disorders, diabetes, cancer, neurological disorders and ulcer as well as for a few demographic factors such age, gender and marital status. Twenty significant associations between chronic conditions and SF-36 domains were observed. After controlling for all chronic conditions, socio-demographic and DIF items, a significant association emerged between cardiovascular disorders and physical functioning, while the association between diabetes and ulcer and general health became nonsignificant. All other associations remained statistically significant. Our findings provide useful information and important implications of DIF on the impact of chronic conditions on HRQoL. We found the impact of DIF with respect to the impact of chronic conditions on HRQoL to be minimal after accounting for measurement bias in this multiracial Asian population.

Autophagy in lung disease pathogenesis and therapeutics

PubMed Central

Ryter, Stefan W.; Choi, Augustine M.K.

2015-01-01

Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy) may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics. PMID:25617802

Bayesian modelling of lung function data from multiple-breath washout tests.

PubMed

Mahar, Robert K; Carlin, John B; Ranganathan, Sarath; Ponsonby, Anne-Louise; Vuillermin, Peter; Vukcevic, Damjan

2018-05-30

Paediatric respiratory researchers have widely adopted the multiple-breath washout (MBW) test because it allows assessment of lung function in unsedated infants and is well suited to longitudinal studies of lung development and disease. However, a substantial proportion of MBW tests in infants fail current acceptability criteria. We hypothesised that a model-based approach to analysing the data, in place of traditional simple empirical summaries, would enable more efficient use of these tests. We therefore developed a novel statistical model for infant MBW data and applied it to 1197 tests from 432 individuals from a large birth cohort study. We focus on Bayesian estimation of the lung clearance index, the most commonly used summary of lung function from MBW tests. Our results show that the model provides an excellent fit to the data and shed further light on statistical properties of the standard empirical approach. Furthermore, the modelling approach enables the lung clearance index to be estimated by using tests with different degrees of completeness, something not possible with the standard approach. Our model therefore allows previously unused data to be used rather than discarded, as well as routine use of shorter tests without significant loss of precision. Beyond our specific application, our work illustrates a number of important aspects of Bayesian modelling in practice, such as the importance of hierarchical specifications to account for repeated measurements and the value of model checking via posterior predictive distributions. Copyright © 2018 John Wiley & Sons, Ltd.

New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies.

PubMed

Nallathamby, Prakash D; Mortensen, Ninell P; Palko, Heather A; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J; Gu, Baohua; Roeder, Ryan K; Wang, Wei; Retterer, Scott T

2015-04-21

Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with (14)C, with a final activity of 0.097 nCi mg(-1) of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials.

New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies†

PubMed Central

Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J.; Gu, Baohua; Roeder, Ryan K.; Wang, Wei; Retterer, Scott T.

2016-01-01

Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90–110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of –35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg–1 of NPs. In chronic studies, the biodistribution profile is tracked using low-level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials. PMID:25790032

New Surface Radiolabeling Schemes of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) for Biodistribution Studies

DOE PAGES

Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; ...

2015-03-02

Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and 10 easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), wasmore » between 90 110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate 15 functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi/mg -1 of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-20 radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and 25 detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials.« less

Protein kinase FgSch9 serves as a mediator of the target of rapamycin and high osmolarity glycerol pathways and regulates multiple stress responses and secondary metabolism in Fusarium graminearum.

PubMed

Gu, Qin; Zhang, Chengqi; Yu, Fangwei; Yin, Yanni; Shim, Won-Bo; Ma, Zhonghua

2015-08-01

Saccharomyces cerevisiae protein kinase Sch9 is one of the downstream effectors of the target of rapamycin (TOR) complex 1 and plays multiple roles in stress resistance, longevity and nutrient sensing. However, the functions of Sch9 orthologs in filamentous fungi, particularly in pathogenic species, have not been characterized to date. Here, we investigated biological and genetic functions of FgSch9 in Fusarium graminearum. The FgSCH9 deletion mutant (ΔFgSch9) was defective in aerial hyphal growth, hyphal branching and conidial germination. The mutant exhibited increased sensitivity to osmotic and oxidative stresses, cell wall-damaging agents, and to rapamycin, while showing increased thermal tolerance. We identified FgMaf1 as one of the FgSch9-interacting proteins that plays an important role in regulating mycotoxin biosynthesis and virulence of F. graminearum. Co-immunoprecipitation and affinity capture-mass spectrometry assays showed that FgSch9 also interacts with FgTor and FgHog1. More importantly, both ΔFgSch9 and FgHog1 null mutant (ΔFgHog1) exhibited increased sensitivity to osmotic and oxidative stresses. This defect was more severe in the FgSch9/FgHog1 double mutant. Taken together, we propose that FgSch9 serves as a mediator of the TOR and high osmolarity glycerol pathways, and regulates vegetative differentiation, multiple stress responses and secondary metabolism in F. graminearum. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

The Importance of the Prenatal Environment in Behavioral Genetics: Introduction to Special Issue.

PubMed

Knopik, Valerie S; Neiderhiser, Jenae M; de Geus, Eco; Boomsma, Dorret

2016-05-01

We introduce and discuss a special issue on prenatal factors in genetics research, that includes 14 papers ranging from studies on chorionicity, smoking during pregnancy, and more general prenatal risks to papers about theory, methods and measurement. There are two review papers, one focused on chorioncity and the second on pre- and perinatal ischemia-hypoxia, that help to frame the state of research in these areas with a focus on the relevance across multiple fields of study. Taken together, these papers clearly demonstrate the importance of considering prenatal environment influences on functioning in offspring across the lifespan while also underscoring the importance of using genetically informed designs as a means to clarify causality.

"Multiple partial recognitions in dynamic equilibrium" in the binding sites of proteins form the molecular basis of promiscuous recognition of structurally diverse ligands.

PubMed

Kohda, Daisuke

2018-04-01

Promiscuous recognition of ligands by proteins is as important as strict recognition in numerous biological processes. In living cells, many short, linear amino acid motifs function as targeting signals in proteins to specify the final destination of the protein transport. In general, the target signal is defined by a consensus sequence containing wild-characters, and hence represented by diverse amino acid sequences. The classical lock-and-key or induced-fit/conformational selection mechanism may not cover all aspects of the promiscuous recognition. On the basis of our crystallographic and NMR studies on the mitochondrial Tom20 protein-presequence interaction, we proposed a new hypothetical mechanism based on "a rapid equilibrium of multiple states with partial recognitions". This dynamic, multiple recognition mode enables the Tom20 receptor to recognize diverse mitochondrial presequences with nearly equal affinities. The plant Tom20 is evolutionally unrelated to the animal Tom20 in our study, but is a functional homolog of the animal/fungal Tom20. NMR studies by another research group revealed that the presequence binding by the plant Tom20 was not fully explained by simple interaction modes, suggesting the presence of a similar dynamic, multiple recognition mode. Circumstantial evidence also suggested that similar dynamic mechanisms may be applicable to other promiscuous recognitions of signal peptides by the SRP54/Ffh and SecA proteins.

Massively parallel sparse matrix function calculations with NTPoly

NASA Astrophysics Data System (ADS)

Dawson, William; Nakajima, Takahito

2018-04-01

We present NTPoly, a massively parallel library for computing the functions of sparse, symmetric matrices. The theory of matrix functions is a well developed framework with a wide range of applications including differential equations, graph theory, and electronic structure calculations. One particularly important application area is diagonalization free methods in quantum chemistry. When the input and output of the matrix function are sparse, methods based on polynomial expansions can be used to compute matrix functions in linear time. We present a library based on these methods that can compute a variety of matrix functions. Distributed memory parallelization is based on a communication avoiding sparse matrix multiplication algorithm. OpenMP task parallellization is utilized to implement hybrid parallelization. We describe NTPoly's interface and show how it can be integrated with programs written in many different programming languages. We demonstrate the merits of NTPoly by performing large scale calculations on the K computer.

Ensemble gene function prediction database reveals genes important for complex I formation in Arabidopsis thaliana.

PubMed

Hansen, Bjoern Oest; Meyer, Etienne H; Ferrari, Camilla; Vaid, Neha; Movahedi, Sara; Vandepoele, Klaas; Nikoloski, Zoran; Mutwil, Marek

2018-03-01

Recent advances in gene function prediction rely on ensemble approaches that integrate results from multiple inference methods to produce superior predictions. Yet, these developments remain largely unexplored in plants. We have explored and compared two methods to integrate 10 gene co-function networks for Arabidopsis thaliana and demonstrate how the integration of these networks produces more accurate gene function predictions for a larger fraction of genes with unknown function. These predictions were used to identify genes involved in mitochondrial complex I formation, and for five of them, we confirmed the predictions experimentally. The ensemble predictions are provided as a user-friendly online database, EnsembleNet. The methods presented here demonstrate that ensemble gene function prediction is a powerful method to boost prediction performance, whereas the EnsembleNet database provides a cutting-edge community tool to guide experimentalists. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Multiple functions of BCL-2 family proteins.

PubMed

Hardwick, J Marie; Soane, Lucian

2013-02-01

BCL-2 family proteins are the regulators of apoptosis, but also have other functions. This family of interacting partners includes inhibitors and inducers of cell death. Together they regulate and mediate the process by which mitochondria contribute to cell death known as the intrinsic apoptosis pathway. This pathway is required for normal embryonic development and for preventing cancer. However, before apoptosis is induced, BCL-2 proteins have critical roles in normal cell physiology related to neuronal activity, autophagy, calcium handling, mitochondrial dynamics and energetics, and other processes of normal healthy cells. The relative importance of these physiological functions compared to their apoptosis functions in overall organismal physiology is difficult to decipher. Apoptotic and noncanonical functions of these proteins may be intertwined to link cell growth to cell death. Disentanglement of these functions may require delineation of biochemical activities inherent to the characteristic three-dimensional shape shared by distantly related viral and cellular BCL-2 family members.

Oligomerization but Not Membrane Bending Underlies the Function of Certain F-BAR Proteins in Cell Motility and Cytokinesis.

PubMed

McDonald, Nathan A; Vander Kooi, Craig W; Ohi, Melanie D; Gould, Kathleen L

2015-12-21

F-BAR proteins function in diverse cellular processes by linking membranes to the actin cytoskeleton. Through oligomerization, multiple F-BAR domains can bend membranes into tubules, though the physiological importance of F-BAR-to-F-BAR assemblies is not yet known. Here, we investigate the F-BAR domain of the essential cytokinetic scaffold, Schizosaccharomyces pombe Cdc15, during cytokinesis. Challenging a widely held view that membrane deformation is a fundamental property of F-BARs, we report that the Cdc15 F-BAR binds, but does not deform, membranes in vivo or in vitro, and six human F-BAR domains-including those from Fer and RhoGAP4-share this property. Nevertheless, tip-to-tip interactions between F-BAR dimers are critical for Cdc15 oligomerization and high-avidity membrane binding, stabilization of contractile ring components at the medial cortex, and the fidelity of cytokinesis. F-BAR oligomerization is also critical for Fer and RhoGAP4 physiological function, demonstrating its broad importance to F-BAR proteins that function without membrane bending. Copyright © 2015 Elsevier Inc. All rights reserved.

The bornavirus-derived human protein EBLN1 promotes efficient cell cycle transit, microtubule organisation and genome stability

PubMed Central

Myers, Katie N.; Barone, Giancarlo; Ganesh, Anil; Staples, Christopher J.; Howard, Anna E.; Beveridge, Ryan D.; Maslen, Sarah; Skehel, J. Mark; Collis, Spencer J.

2016-01-01

It was recently discovered that vertebrate genomes contain multiple endogenised nucleotide sequences derived from the non-retroviral RNA bornavirus. Strikingly, some of these elements have been evolutionary maintained as open reading frames in host genomes for over 40 million years, suggesting that some endogenised bornavirus-derived elements (EBL) might encode functional proteins. EBLN1 is one such element established through endogenisation of the bornavirus N gene (BDV N). Here, we functionally characterise human EBLN1 as a novel regulator of genome stability. Cells depleted of human EBLN1 accumulate DNA damage both under non-stressed conditions and following exogenously induced DNA damage. EBLN1-depleted cells also exhibit cell cycle abnormalities and defects in microtubule organisation as well as premature centrosome splitting, which we attribute in part, to improper localisation of the nuclear envelope protein TPR. Our data therefore reveal that human EBLN1 possesses important cellular functions within human cells, and suggest that other EBLs present within vertebrate genomes may also possess important cellular functions. PMID:27739501

Phosphorylation is required for the pathogen defense function of the Arabidopsis PEN3 ABC transporter.

PubMed

Underwood, William; Somerville, Shauna C

2017-10-03

The Arabidopsis PEN3 ABC transporter accumulates at sites of pathogen detection, where it is involved in defense against a number of pathogens. Perception of PAMPs by pattern recognition receptors initiates recruitment of PEN3 and also leads to PEN3 phosphorylation at multiple amino acid residues. Whether PAMP-induced phosphorylation of PEN3 is important for its defense function or focal recruitment has not been addressed. In this study, we evaluated the role of PEN3 phosphorylation in modulating the localization and defense function of the transporter. We report that PEN3 phosphorylation is critical for its function in defense, but dispensable for recruitment to powdery mildew penetration sites. These results indicate that PAMP-induced phosphorylation is likely to regulate the transport activity of PEN3.

Segregated Systems of Human Brain Networks.

PubMed

Wig, Gagan S

2017-12-01

The organization of the brain network enables its function. Evaluation of this organization has revealed that large-scale brain networks consist of multiple segregated subnetworks of interacting brain areas. Descriptions of resting-state network architecture have provided clues for understanding the functional significance of these segregated subnetworks, many of which correspond to distinct brain systems. The present report synthesizes accumulating evidence to reveal how maintaining segregated brain systems renders the human brain network functionally specialized, adaptable to task demands, and largely resilient following focal brain damage. The organizational properties that support system segregation are harmonious with the properties that promote integration across the network, but confer unique and important features to the brain network that are central to its function and behavior. Copyright © 2017 Elsevier Ltd. All rights reserved.

Global environmental change effects on ecosystems: the importance of land-use legacies.

PubMed

Perring, Michael P; De Frenne, Pieter; Baeten, Lander; Maes, Sybryn L; Depauw, Leen; Blondeel, Haben; Carón, María M; Verheyen, Kris

2016-04-01

One of the major challenges in ecology is to predict how multiple global environmental changes will affect future ecosystem patterns (e.g. plant community composition) and processes (e.g. nutrient cycling). Here, we highlight arguments for the necessary inclusion of land-use legacies in this endeavour. Alterations in resources and conditions engendered by previous land use, together with influences on plant community processes such as dispersal, selection, drift and speciation, have steered communities and ecosystem functions onto trajectories of change. These trajectories may be modulated by contemporary environmental changes such as climate warming and nitrogen deposition. We performed a literature review which suggests that these potential interactions have rarely been investigated. This crucial oversight is potentially due to an assumption that knowledge of the contemporary state allows accurate projection into the future. Lessons from other complex dynamic systems, and the recent recognition of the importance of previous conditions in explaining contemporary and future ecosystem properties, demand the testing of this assumption. Vegetation resurvey databases across gradients of land use and environmental change, complemented by rigorous experiments, offer a means to test for interactions between land-use legacies and multiple environmental changes. Implementing these tests in the context of a trait-based framework will allow biologists to synthesize compositional and functional ecosystem responses. This will further our understanding of the importance of land-use legacies in determining future ecosystem properties, and soundly inform conservation and restoration management actions. © 2015 John Wiley & Sons Ltd.

The Making of a Skull Base Team and the Value of Multidisciplinary Approach in the Management of Sinonasal and Ventral Skull Base Malignancies.

PubMed

Snyderman, Carl H; Wang, Eric W; Fernandez-Miranda, Juan C; Gardner, Paul A

2017-04-01

The management of sinonasal and ventral skull base malignancies is best performed by a team. Although the composition of the team may vary, it is important to have multidisciplinary representation. There are multiple obstacles, both individual and institutional, that must be overcome to develop a highly functioning team. Adequate training is an important part of team-building and can be fostered with surgical telementoring. A quality improvement program should be incorporated into the activities of a skull base team. Copyright © 2016 Elsevier Inc. All rights reserved.

How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?

PubMed

Dempsey, D'Maris Amick; Klessig, Daniel F

2017-03-23

Salicylic acid (SA) is an important plant hormone that regulates many aspects of plant growth and development, as well as resistance to (a)biotic stress. Efforts to identify SA effector proteins have revealed that SA binds to and alters the activity of multiple plant proteins-this represents a shift from the paradigm that hormones mediate their functions via one or a few receptors. SA and its derivatives also have multiple targets in animals; some of these proteins, like their plant counterparts, are associated with pathological processes. Together, these findings suggest that SA exerts its defense-associated effects in both kingdoms via a large number of targets.

The β-Arrestins: Multifunctional Regulators of G Protein-coupled Receptors.

PubMed

Smith, Jeffrey S; Rajagopal, Sudarshan

2016-04-22

The β-arrestins (βarrs) are versatile, multifunctional adapter proteins that are best known for their ability to desensitize G protein-coupled receptors (GPCRs), but also regulate a diverse array of cellular functions. To signal in such a complex fashion, βarrs adopt multiple conformations and are regulated at multiple levels to differentially activate downstream pathways. Recent structural studies have demonstrated that βarrs have a conserved structure and activation mechanism, with plasticity of their structural fold, allowing them to adopt a wide array of conformations. Novel roles for βarrs continue to be identified, demonstrating the importance of these dynamic regulators of cellular signaling. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Estradiol Membrane-Initiated Signaling in the Brain Mediates Reproduction.

PubMed

Micevych, Paul E; Mermelstein, Paul G; Sinchak, Kevin

2017-11-01

Over the past few years our understanding of estrogen signaling in the brain has expanded rapidly. Estrogens are synthesized in the periphery and in the brain, acting on multiple receptors to regulate gene transcription, neural function, and behavior. Various estrogen-sensitive signaling pathways often operate in concert within the same cell, increasing the complexity of the system. In females, estrogen concentrations fluctuate over the estrous/menstrual cycle, dynamically modulating estrogen receptor (ER) expression, activity, and trafficking. These dynamic changes influence multiple behaviors but are particularly important for reproduction. Using the female rodent model, we review our current understanding of estradiol signaling in the regulation of sexual receptivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI

DTIC Science & Technology

2015-10-01

Page | 2 AWARD NUMBER: W81XWH-13-1-0464 TITLE: Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional MRI...Sep 2014 – 29 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Detection of Brain Reorganization in Pediatric Multiple Sclerosis Using Functional...findings include: 1) detection of brain organization in a cohort of 24 pediatric onset multiple sclerosis patients (POMS) and 25 healthy controls

Expression of the Antioxidative Enzyme Peroxiredoxin 2 in Multiple Sclerosis Lesions in Relation to Inflammation

PubMed Central

Voigt, David; Scheidt, Uta; Derfuss, Tobias; Brück, Wolfgang; Junker, Andreas

2017-01-01

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, characterized by demyelination and axonal damage as well as neuronal degeneration. Since oxygen-derived free radicals are an important factor leading to tissue damage in inflammatory multiple sclerosis (MS) lesions, research on antioxidative systems is essential to identify endogenous factors which can possibly counteract oxidative damage. As an important scavenging enzyme family, peroxiredoxins (PRDXs) play a crucial role in preventing oxidative damage; however little is known about their expression and function in MS lesions. In the present study we examined the expression of PRDX2 in white matter lesions of MS patients with long-standing, chronic disease. PRDX2 expression was investigated by immunohistochemistry in the context of oxidative stress and inflammation (determined by microglia/macrophage and T cell infiltration) in ten MS autopsy cases as well as seven control autopsy cases. PRDX2 was found to be upregulated in white matter MS lesions mainly in astrocytes, and its expression level was positively correlated with the degree of inflammation and oxidative stress. Our data suggest that PRDX2 expression contributes to the resistance of astrocytes against oxidative damage. PMID:28375164

Faunal assemblages and multi-scale habitat patterns in headwater tributaries of the South Fork Trinity River - an unregulated river embedded within a multiple-use landscape

Treesearch

H. H. Jr. Welsh; J. J. G. R. Hodgson; J. M. Emlen Duda

2010-01-01

Headwaters can represent 80% of stream kilometers in a watershed, and they also have unique physical and biological properties that have only recently been recognized for their importance in sustaining healthy functioning stream networks and their ecological services. We sampled 60 headwater tributaries in the South Fork Trinity River, a 2,430 km2...

Charting organellar importomes by quantitative mass spectrometry

PubMed Central

Peikert, Christian D.; Mani, Jan; Morgenstern, Marcel; Käser, Sandro; Knapp, Bettina; Wenger, Christoph; Harsman, Anke; Oeljeklaus, Silke; Schneider, André; Warscheid, Bettina

2017-01-01

Protein import into organelles is essential for all eukaryotes and facilitated by multi-protein translocation machineries. Analysing whether a protein is transported into an organelle is largely restricted to single constituents. This renders knowledge about imported proteins incomplete, limiting our understanding of organellar biogenesis and function. Here we introduce a method that enables charting an organelle's importome. The approach relies on inducible RNAi-mediated knockdown of an essential subunit of a translocase to impair import and quantitative mass spectrometry. To highlight its potential, we established the mitochondrial importome of Trypanosoma brucei, comprising 1,120 proteins including 331 new candidates. Furthermore, the method allows for the identification of proteins with dual or multiple locations and the substrates of distinct protein import pathways. We demonstrate the specificity and versatility of this ImportOmics method by targeting import factors in mitochondria and glycosomes, which demonstrates its potential for globally studying protein import and inventories of organelles. PMID:28485388

Return to work after severe multiple injuries: a multidimensional approach on status 1 and 2 years postinjury.

PubMed

Soberg, Helene Lundgaard; Finset, Arnstein; Bautz-Holter, Erik; Sandvik, Leiv; Roise, Olav

2007-02-01

The assessment of factors associated with return to work (RTW) after multiple trauma is important in trauma research. Goals in rehabilitation should comprise RTW. The purpose of this study was to examine the RTW rate and which factors predicted RTW for patients with severe multiple injuries using a prospective cohort design. In all, 100 patients with a New Injury Severity Score (NISS) >15, aged 18 to 67 years and admitted to a trauma referral center, were included starting January 2002 through June 2003. Outcomes were assessed 6 weeks after discharge and 1 and 2 years postinjury. Instruments were the Brief Approach/Avoidance Coping Questionnaire, Multidimensional Health Locus of Control, Short Form-36, the World Health Organization Disability Assessment Schedule II, and a cognitive function scale (COG). Mean age was 34.5 years (SD 13.5), 83% were male, and 66% were blue-collar workers. Mean NISS was 35.1 (SD 12.7). At 1 year, 28% achieved complete RTW, 43% at 2 years. Mean time back to work was 12.8 months (SD 5.9). Differences between the RTW and not complete RTW (NRTW) groups concerned personal and demographic variables, and physical and psychosocial functioning. Survival analysis showed that risk factors for NRTW were lower education, length of stay in hospital/rehabilitation >20 weeks, and low social functioning shortly after the return home. The majority of the patients had not completely returned to work 2 years postinjury. Demographic and injury related factors and social functioning were significant predictors of RTW status.

Associations Between Fatigue and Disability, Functional Mobility, Depression, and Quality of Life in People with Multiple Sclerosis

PubMed Central

Bush, Steffani; Gappmaier, Eduard

2016-01-01

Background: Fatigue is a common symptom in people with multiple sclerosis (MS), but its associations with disability, functional mobility, depression, and quality of life (QOL) remain unclear. We aimed to determine the associations between different levels of fatigue and disability, functional mobility, depression, and physical and mental QOL in people with MS. Methods: Eighty-nine individuals with MS (mean [SD] disease duration = 13.6 [9.8] years, mean [SD] Expanded Disability Status Scale [EDSS] score = 5.3 [1.5]) and no concurrent relapses were retrospectively analyzed. Participants were divided into two groups based on five-item Modified Fatigue Impact Scale (MFIS-5) scores: group LF (n = 32, MFIS-5 score ≤10 [low levels of fatigue]) and group HF (n = 57, MFIS-5 score >10 [high levels of fatigue]). Results: Sixty-four percent of the sample reported high levels of fatigue. Compared with group LF, group HF demonstrated significantly (P < .05) greater impairments in the Timed Up and Go test, Activities-specific Balance Confidence scale, and 12-item Multiple Sclerosis Walking Scale scores; depression; and QOL but not in the EDSS scores, which were not significantly different between groups. Conclusions: Fatigue was found to be a predominant symptom in the study participants. Individuals reporting higher levels of fatigue concomitantly exhibited greater impairments in functional mobility, depression, and physical and mental QOL. Disability was not found to be related to level of fatigue. These findings can be important for appropriate assessment and management of individuals with MS with fatigue. PMID:27134580

Wetlands as large-scale nature-based solutions: status and future challenges for research and management

NASA Astrophysics Data System (ADS)

Thorslund, Josefin; Jarsjö, Jerker; Destouni, Georgia

2017-04-01

Wetlands are often considered as nature-based solutions that can provide a multitude of services of great social, economic and environmental value to humankind. The services may include recreation, greenhouse gas sequestration, contaminant retention, coastal protection, groundwater level and soil moisture regulation, flood regulation and biodiversity support. Changes in land-use, water use and climate can all impact wetland functions and occur at scales extending well beyond the local scale of an individual wetland. However, in practical applications, management decisions usually regard and focus on individual wetland sites and local conditions. To understand the potential usefulness and services of wetlands as larger-scale nature-based solutions, e.g. for mitigating negative impacts from large-scale change pressures, one needs to understand the combined function multiple wetlands at the relevant large scales. We here systematically investigate if and to what extent research so far has addressed the large-scale dynamics of landscape systems with multiple wetlands, which are likely to be relevant for understanding impacts of regional to global change. Our investigation regards key changes and impacts of relevance for nature-based solutions, such as large-scale nutrient and pollution retention, flow regulation and coastal protection. Although such large-scale knowledge is still limited, evidence suggests that the aggregated functions and effects of multiple wetlands in the landscape can differ considerably from those observed at individual wetlands. Such scale differences may have important implications for wetland function-effect predictability and management under large-scale change pressures and impacts, such as those of climate change.

Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species.

PubMed

Pan, Xu; Song, Yao-Bin; Liu, Guo-Fang; Hu, Yu-Kun; Ye, Xue-Hua; Cornwell, William K; Prinzing, Andreas; Dong, Ming; Cornelissen, Johannes H C

2015-08-18

In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such contribution varies among plant species at given irradiance regime, (2) whether interspecific variation in such contribution correlates with interspecific variation in the decomposition rate under shade; and (3) whether this correlation can be explained by leaf traits. We conducted a factorial experiment to determine the effects of solar radiation and environmental moisture for the mass loss and the decomposition constant k-values of 13 species litters collected in Northern China. The contribution of solar radiation to leaf litter decomposition varied significantly among species. Solar radiation accelerated decomposition in particular in the species that already decompose quickly under shade. Functional traits, notably specific leaf area, might predict the interspecific variation in that contribution. Our results provide the first empirical evidence for how the effect of solar radiation on decomposition varies among multiple species. Thus, the effect of solar radiation on the carbon flux between biosphere and atmosphere may depend on the species composition of the vegetation.

Functional traits drive the contribution of solar radiation to leaf litter decomposition among multiple arid-zone species

PubMed Central

Pan, Xu; Song, Yao-Bin; Liu, Guo-Fang; Hu, Yu-Kun; Ye, Xue-Hua; Cornwell, William K.; Prinzing, Andreas; Dong, Ming; Cornelissen, Johannes H.C.

2015-01-01

In arid zones, strong solar radiation has important consequences for ecosystem processes. To better understand carbon and nutrient dynamics, it is important to know the contribution of solar radiation to leaf litter decomposition of different arid-zone species. Here we investigated: (1) whether such contribution varies among plant species at given irradiance regime, (2) whether interspecific variation in such contribution correlates with interspecific variation in the decomposition rate under shade; and (3) whether this correlation can be explained by leaf traits. We conducted a factorial experiment to determine the effects of solar radiation and environmental moisture for the mass loss and the decomposition constant k-values of 13 species litters collected in Northern China. The contribution of solar radiation to leaf litter decomposition varied significantly among species. Solar radiation accelerated decomposition in particular in the species that already decompose quickly under shade. Functional traits, notably specific leaf area, might predict the interspecific variation in that contribution. Our results provide the first empirical evidence for how the effect of solar radiation on decomposition varies among multiple species. Thus, the effect of solar radiation on the carbon flux between biosphere and atmosphere may depend on the species composition of the vegetation. PMID:26282711

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7.

PubMed

Gullett, Jessica M; Bible, Amber; Alexandre, Gladys

2017-07-01

Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense , Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. Copyright © 2017 American Society for Microbiology.

Distinct Domains of CheA Confer Unique Functions in Chemotaxis and Cell Length in Azospirillum brasilense Sp7

PubMed Central

Gullett, Jessica M.

2017-01-01

ABSTRACT Chemotaxis is the movement of cells in response to gradients of diverse chemical cues. Motile bacteria utilize a conserved chemotaxis signal transduction system to bias their motility and navigate through a gradient. A central regulator of chemotaxis is the histidine kinase CheA. This cytoplasmic protein interacts with membrane-bound receptors, which assemble into large polar arrays, to propagate the signal. In the alphaproteobacterium Azospirillum brasilense, Che1 controls transient increases in swimming speed during chemotaxis, but it also biases the cell length at division. However, the exact underlying molecular mechanisms for Che1-dependent control of multiple cellular behaviors are not known. Here, we identify specific domains of the CheA1 histidine kinase implicated in modulating each of these functions. We show that CheA1 is produced in two isoforms: a membrane-anchored isoform produced as a fusion with a conserved seven-transmembrane domain of unknown function (TMX) at the N terminus and a soluble isoform similar to prototypical CheA. Site-directed and deletion mutagenesis combined with behavioral assays confirm the role of CheA1 in chemotaxis and implicate the TMX domain in mediating changes in cell length. Fluorescence microscopy further reveals that the membrane-anchored isoform is distributed around the cell surface while the soluble isoform localizes at the cell poles. Together, the data provide a mechanism for the role of Che1 in controlling multiple unrelated cellular behaviors via acquisition of a new domain in CheA1 and production of distinct functional isoforms. IMPORTANCE Chemotaxis provides a significant competitive advantage to bacteria in the environment, and this function has been transferred laterally multiple times, with evidence of functional divergence in different genomic contexts. The molecular principles that underlie functional diversification of chemotaxis in various genomic contexts are unknown. Here, we provide a molecular mechanism by which a single CheA protein controls two unrelated functions: chemotaxis and cell length. Acquisition of this multifunctionality is seemingly a recent evolutionary event. The findings illustrate a mechanism by which chemotaxis function may be co-opted to regulate additional cellular functions. PMID:28416707

Domains of importance for parents, medical professionals and youth with cerebral palsy considering treatment outcomes.

PubMed

Vargus-Adams, J N; Martin, L K

2011-03-01

The aim of this study was to assess the domains of importance in therapeutic intervention for cerebral palsy (CP) using categories of the International Classification of Functioning, Disability, and Health - Children and Youth Version (ICF-CY). A total of 17 youth, 19 parents and 39 medical professionals responded to the open-ended query: 'What are the things you find most important to consider when you evaluate the effects of an intervention for yourself/your child/your patient with cerebral palsy?' Surveys were either mailed or conducted on-line. Responses were coded by two reviewers using the ICF-CY and discrepancies were resolved. Responses were distributed across the ICF-CY domains of Body Functions and Structures, Activities and Participation, and Environmental Factors, as well as non-ICF-CY concepts including quality of life. The most common responses overall were pain, motor function, mobility, community life and public services. Youth identified strength, gait pattern, hand/arm use and use of assistive technologies as priorities whereas parents were concerned with motor function, communication, mobility and provision of public services. Medical professionals listed pain, function, mobility, community life and participation most often. All surveyed groups indicate a desire to see changes in body functions and structures (pain, mental function, strength, movement), activities and participation (communication, hand/arm use, walking, school, recreation/community life) and quality of life following therapeutic interventions for CP. These results demonstrate the multiple, varied concerns regarding CP across the spectrum of functioning and health. © 2010 Blackwell Publishing Ltd.

Physiological and pathological functions of acid-sensing ion channels in the central nervous system

PubMed Central

Chu, Xiang-Ping; Xiong, Zhi-Gang

2012-01-01

Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain ischemia, multiple sclerosis, epileptic seizures, and malignant glioma. Thus, targeting these channels may lead to novel therapeutic interventions for neurological disorders. The goal of this review is to provide an update on recent advances in our understanding of the functions of ASICs in the CNS. PMID:22204324

Potential importance of B cells in aging and aging-associated neurodegenerative diseases.

PubMed

Biragyn, Arya; Aliseychik, Maria; Rogaev, Evgeny

2017-04-01

Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases.

Heterogeneity of reward mechanisms.

PubMed

Lajtha, A; Sershen, H

2010-06-01

The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli and that the mechanism is relatively simple. The presently available information shows that the mechanisms involved are more complex and have multiple elements. Multiple brain regions, multiple receptors, multiple distinct neurons, multiple transmitters, multiple transporters, circuits, peptides, proteins, metabolism of transmitters, and phosphorylation, all participate in reward mechanisms. The system is variable, is changed during development, is sex-dependent, and is influenced by genetic differences. Not all of the elements participate in the reward of all stimuli. Different set of mechanisms are involved in the reward of different drugs of abuse, yet different mechanisms in the reward of natural stimuli such as food or sexual activity; thus there are different systems that distinguish different stimuli. Separate functions of the reward system such as anticipation, evaluation, consummation and identification; all contain function-specific elements. The level of the stimulus also influences the participation of the elements of the reward system, there are possible reactions to even below threshold stimuli, and excessive stimuli can change reward to aversion involving parts of the system. Learning and memory of past reward is an important integral element of reward and addictive behavior. Many of the reward elements are altered by repeated or chronic stimuli, and chronic exposure to one drug is likely to alter the response to another stimulus. To evaluate and identify the reward stimulus thus requires heterogeneity of the reward components in the brain.

DNA is structured as a linear "jigsaw puzzle" in the genomes of Arabidopsis, rice, and budding yeast.

PubMed

Liu, Yun-Hua; Zhang, Meiping; Wu, Chengcang; Huang, James J; Zhang, Hong-Bin

2014-01-01

Knowledge of how a genome is structured and organized from its constituent elements is crucial to understanding its biology and evolution. Here, we report the genome structuring and organization pattern as revealed by systems analysis of the sequences of three model species, Arabidopsis, rice and yeast, at the whole-genome and chromosome levels. We found that all fundamental function elements (FFE) constituting the genomes, including genes (GEN), DNA transposable elements (DTE), retrotransposable elements (RTE), simple sequence repeats (SSR), and (or) low complexity repeats (LCR), are structured in a nonrandom and correlative manner, thus leading to a hypothesis that the DNA of the species is structured as a linear "jigsaw puzzle". Furthermore, we showed that different FFE differ in their importance in the formation and evolution of the DNA jigsaw puzzle structure between species. DTE and RTE play more important roles than GEN, LCR, and SSR in Arabidopsis, whereas GEN and RTE play more important roles than LCR, SSR, and DTE in rice. The genes having multiple recognized functions play more important roles than those having single functions. These results provide useful knowledge necessary for better understanding genome biology and evolution of the species and for effective molecular breeding of rice.

Splicing regulatory factors, ageing and age-related disease.

PubMed

Latorre, Eva; Harries, Lorna W

2017-07-01

Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Reliability based design including future tests and multiagent approaches

NASA Astrophysics Data System (ADS)

Villanueva, Diane

The initial stages of reliability-based design optimization involve the formulation of objective functions and constraints, and building a model to estimate the reliability of the design with quantified uncertainties. However, even experienced hands often overlook important objective functions and constraints that affect the design. In addition, uncertainty reduction measures, such as tests and redesign, are often not considered in reliability calculations during the initial stages. This research considers two areas that concern the design of engineering systems: 1) the trade-off of the effect of a test and post-test redesign on reliability and cost and 2) the search for multiple candidate designs as insurance against unforeseen faults in some designs. In this research, a methodology was developed to estimate the effect of a single future test and post-test redesign on reliability and cost. The methodology uses assumed distributions of computational and experimental errors with re-design rules to simulate alternative future test and redesign outcomes to form a probabilistic estimate of the reliability and cost for a given design. Further, it was explored how modeling a future test and redesign provides a company an opportunity to balance development costs versus performance by simultaneously designing the design and the post-test redesign rules during the initial design stage. The second area of this research considers the use of dynamic local surrogates, or surrogate-based agents, to locate multiple candidate designs. Surrogate-based global optimization algorithms often require search in multiple candidate regions of design space, expending most of the computation needed to define multiple alternate designs. Thus, focusing on solely locating the best design may be wasteful. We extended adaptive sampling surrogate techniques to locate multiple optima by building local surrogates in sub-regions of the design space to identify optima. The efficiency of this method was studied, and the method was compared to other surrogate-based optimization methods that aim to locate the global optimum using two two-dimensional test functions, a six-dimensional test function, and a five-dimensional engineering example.

Scheduling optimization of design stream line for production research and development projects

NASA Astrophysics Data System (ADS)

Liu, Qinming; Geng, Xiuli; Dong, Ming; Lv, Wenyuan; Ye, Chunming

2017-05-01

In a development project, efficient design stream line scheduling is difficult and important owing to large design imprecision and the differences in the skills and skill levels of employees. The relative skill levels of employees are denoted as fuzzy numbers. Multiple execution modes are generated by scheduling different employees for design tasks. An optimization model of a design stream line scheduling problem is proposed with the constraints of multiple executive modes, multi-skilled employees and precedence. The model considers the parallel design of multiple projects, different skills of employees, flexible multi-skilled employees and resource constraints. The objective function is to minimize the duration and tardiness of the project. Moreover, a two-dimensional particle swarm algorithm is used to find the optimal solution. To illustrate the validity of the proposed method, a case is examined in this article, and the results support the feasibility and effectiveness of the proposed model and algorithm.

Maintaining Bone Health in Patients With Multiple Myeloma: Survivorship Care Plan of the International Myeloma Foundation Nurse Leadership Board

PubMed Central

Miceli, Teresa S.; Colson, Kathleen; Faiman, Beth M.; Miller, Kena; Tariman, Joseph D.

2014-01-01

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice. PMID:21816707

Pair Cascades and Deathlines in Magnetic Fields with Offset Polar Caps

NASA Technical Reports Server (NTRS)

Harding, Alice K.; Muslimov, Alex G.

2012-01-01

We present results of electron-positron pair cascade simulations in a dipole magnetic field whose polar cap is offset from the dipole axis. In such a field geometry, the polar cap is displaced a small fraction of the neutron star radius from the star symmetry axis and the field line radius of curvature is modified. Using the modified parallel electric field near the offset polar cap, we simulate pair cascades to determine the pair deathlines and pair multiplicities as a function of the offset. We find that the pair multiplicity can change dr;unatically with a modest offset, with a significant increase on one side of the polar cap. Lower pair deathlines allow a larger fraction of the pulsar population, that include old and millisecond pulsars, to produce cascades with high multiplicity. The results have some important implications for pulsar particle production, high-energy emission and cosmic-ray contribution.

Maintaining bone health in patients with multiple myeloma: survivorship care plan of the International Myeloma Foundation Nurse Leadership Board.

PubMed

Miceli, Teresa S; Colson, Kathleen; Faiman, Beth M; Miller, Kena; Tariman, Joseph D

2011-08-01

About 90% of individuals with multiple myeloma will develop osteolytic bone lesions from increased osteoclastic and decreased osteoblastic activity. Severe morbidities from pathologic fractures and other skeletal events can lead to poor circulation, blood clots, muscle wasting, compromised performance status, and overall poor survival. Supportive care targeting bone disease is an essential adjunct to antimyeloma therapy. In addition, the maintenance of bone health in patients with multiple myeloma can significantly improve quality of life. Oncology nurses and other healthcare providers play a central role in the management of bone disease and maintenance throughout the course of treatment. Safe administration of bisphosphonates, promotion of exercise, maintenance of adequate nutrition, vitamin and mineral supplementation, scheduled radiographic examinations, and monitoring of bone complications are among the important functions that oncology nurses and healthcare providers perform in clinical practice.

The Use of Cannabis and Cannabinoids in Treating Symptoms of Multiple Sclerosis: a Systematic Review of Reviews.

PubMed

Nielsen, Suzanne; Germanos, Rada; Weier, Megan; Pollard, John; Degenhardt, Louisa; Hall, Wayne; Buckley, Nicholas; Farrell, Michael

2018-02-13

Pharmaceutical cannabinoids such as nabiximols, nabilone and dronabinol, and plant-based cannabinoids have been investigated for their therapeutic potential in treating multiple sclerosis (MS) symptoms. This review of reviews aimed to synthesise findings from high quality systematic reviews that examined the safety and effectiveness of cannabinoids in multiple sclerosis. We examined the outcomes of disability and disability progression, pain, spasticity, bladder function, tremor/ataxia, quality of life and adverse effects. We identified 11 eligible systematic reviews providing data from 32 studies, including 10 moderate to high quality RCTs. Five reviews concluded that there was sufficient evidence that cannabinoids may be effective for symptoms of pain and/or spasticity in MS. Few reviews reported conclusions for other symptoms. Recent high quality reviews find cannabinoids may have modest effects in MS for pain or spasticity. Future research should include studies with non-cannabinoid comparators; this is an important gap in the evidence.

Multi-scale modularity and motif distributional effect in metabolic networks.

PubMed

Gao, Shang; Chen, Alan; Rahmani, Ali; Zeng, Jia; Tan, Mehmet; Alhajj, Reda; Rokne, Jon; Demetrick, Douglas; Wei, Xiaohui

2016-01-01

Metabolism is a set of fundamental processes that play important roles in a plethora of biological and medical contexts. It is understood that the topological information of reconstructed metabolic networks, such as modular organization, has crucial implications on biological functions. Recent interpretations of modularity in network settings provide a view of multiple network partitions induced by different resolution parameters. Here we ask the question: How do multiple network partitions affect the organization of metabolic networks? Since network motifs are often interpreted as the super families of evolved units, we further investigate their impact under multiple network partitions and investigate how the distribution of network motifs influences the organization of metabolic networks. We studied Homo sapiens, Saccharomyces cerevisiae and Escherichia coli metabolic networks; we analyzed the relationship between different community structures and motif distribution patterns. Further, we quantified the degree to which motifs participate in the modular organization of metabolic networks.

Predicting the cumulative effect of multiple disturbances on seagrass connectivity.

PubMed

Grech, Alana; Hanert, Emmanuel; McKenzie, Len; Rasheed, Michael; Thomas, Christopher; Tol, Samantha; Wang, Mingzhu; Waycott, Michelle; Wolter, Jolan; Coles, Rob

2018-03-15

The rate of exchange, or connectivity, among populations effects their ability to recover after disturbance events. However, there is limited information on the extent to which populations are connected or how multiple disturbances affect connectivity, especially in coastal and marine ecosystems. We used network analysis and the outputs of a biophysical model to measure potential functional connectivity and predict the impact of multiple disturbances on seagrasses in the central Great Barrier Reef World Heritage Area (GBRWHA), Australia. The seagrass networks were densely connected, indicating that seagrasses are resilient to the random loss of meadows. Our analysis identified discrete meadows that are important sources of seagrass propagules and that serve as stepping stones connecting various different parts of the network. Several of these meadows were close to urban areas or ports and likely to be at risk from coastal development. Deep water meadows were highly connected to coastal meadows and may function as a refuge, but only for non-foundation species. We evaluated changes to the structure and functioning of the seagrass networks when one or more discrete meadows were removed due to multiple disturbance events. The scale of disturbance required to disconnect the seagrass networks into two or more components was on average >245 km, about half the length of the metapopulation. The densely connected seagrass meadows of the central GBRWHA are not limited by the supply of propagules; therefore, management should focus on improving environmental conditions that support natural seagrass recruitment and recovery processes. Our study provides a new framework for assessing the impact of global change on the connectivity and persistence of coastal and marine ecosystems. Without this knowledge, management actions, including coastal restoration, may prove unnecessary and be unsuccessful. © 2018 John Wiley & Sons Ltd.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation.

PubMed

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H; Yang, Rui; Killela, Patrick J; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Liang, Junbo; Wang, Sizhen; Jiao, Yuchen; Yan, Hai; Tao, Hou-Quan

2015-05-01

Several somatic mutation hotspots were recently identified in the telomerase reverse transcriptase (TERT) promoter region in human cancers. Large scale studies of these mutations in multiple tumour types are limited, in particular in Asian populations. This study aimed to: analyse TERT promoter mutations in multiple tumour types in a large Chinese patient cohort, investigate novel tumour types and assess the functional significance of the mutations. TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumour types and 799 tumour tissues from Chinese cancer patients. Thymic epithelial tumours, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR), telomerase activity by the telomeric repeat amplification protocol (TRAP) assay and promoter activity by the luciferase reporter assay. TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%) and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in gastrointestinal stromal tumour (GIST), thymic epithelial tumours, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. TERT promoter mutations are frequent in multiple tumour types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumourigenesis, making them potential therapeutic targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumor types are associated with increased TERT expression and telomerase activation

PubMed Central

Huang, Dong-Sheng; Wang, Zhaohui; He, Xu-Jun; Diplas, Bill H.; Yang, Rui; Killela, Patrick J.; Liang, Junbo; Meng, Qun; Ye, Zai-Yuan; Wang, Wei; Jiang, Xiao-Ting; Xu, Li; He, Xiang-Lei; Zhao, Zhong-Sheng; Xu, Wen-Juan; Wang, Hui-Ju; Ma, Ying-Yu; Xia, Ying-Jie; Li, Li; Zhang, Ru-Xuan; Jin, Tao; Zhao, Zhong-Kuo; Xu, Ji; Yu, Sheng; Wu, Fang; Wang, Si-Zhen; Jiao, Yu-Chen; Yan, Hai; Tao, Hou-Quan

2015-01-01

Background Several somatic mutation hotspots were recently identified in the TERT promoter region in human cancers. Large scale studies of these mutations in multiple tumor types are limited, in particular in Asian populations. This study aimed to: analyze TERT promoter mutations in multiple tumor types in a large Chinese patient cohort, investigate novel tumor types and assess the functional significance of the mutations. Methods TERT promoter mutation status was assessed by Sanger sequencing for 13 different tumor types and 799 tumor tissues from Chinese cancer patients. Thymic epithelial tumors, gastrointestinal leiomyoma, and gastric schwannoma were included, for which the TERT promoter has not been previously sequenced. Functional studies included TERT expression by RT-qPCR, telomerase activity by the TRAP assay, and promoter activity by the luciferase reporter assay. Results TERT promoter mutations were highly frequent in glioblastoma (83.9%), urothelial carcinoma (64.5%), oligodendroglioma (70.0%), medulloblastoma (33.3%), and hepatocellular carcinoma (31.4%). C228T and C250T were the most common mutations. In urothelial carcinoma, several novel rare mutations were identified. TERT promoter mutations were absent in GIST, thymic epithelial tumors, gastrointestinal leiomyoma, gastric schwannoma, cholangiocarcinoma, gastric and pancreatic cancer. TERT promoter mutations highly correlated with upregulated TERT mRNA expression and telomerase activity in adult gliomas. These mutations differentially enhanced the transcriptional activity of the TERT core promoter. Conclusions TERT promoter mutations are frequent in multiple tumor types and have similar distributions in Chinese cancer patients. The functional significance of these mutations reflect the importance to telomere maintenance and hence tumorigenesis, making them potential therapeutic targets. PMID:25843513

Why Is the Correlation between Gene Importance and Gene Evolutionary Rate So Weak?

PubMed Central

Wang, Zhi; Zhang, Jianzhi

2009-01-01

One of the few commonly believed principles of molecular evolution is that functionally more important genes (or DNA sequences) evolve more slowly than less important ones. This principle is widely used by molecular biologists in daily practice. However, recent genomic analysis of a diverse array of organisms found only weak, negative correlations between the evolutionary rate of a gene and its functional importance, typically measured under a single benign lab condition. A frequently suggested cause of the above finding is that gene importance determined in the lab differs from that in an organism's natural environment. Here, we test this hypothesis in yeast using gene importance values experimentally determined in 418 lab conditions or computationally predicted for 10,000 nutritional conditions. In no single condition or combination of conditions did we find a much stronger negative correlation, which is explainable by our subsequent finding that always-essential (enzyme) genes do not evolve significantly more slowly than sometimes-essential or always-nonessential ones. Furthermore, we verified that functional density, approximated by the fraction of amino acid sites within protein domains, is uncorrelated with gene importance. Thus, neither the lab-nature mismatch nor a potentially biased among-gene distribution of functional density explains the observed weakness of the correlation between gene importance and evolutionary rate. We conclude that the weakness is factual, rather than artifactual. In addition to being weakened by population genetic reasons, the correlation is likely to have been further weakened by the presence of multiple nontrivial rate determinants that are independent from gene importance. These findings notwithstanding, we show that the principle of slower evolution of more important genes does have some predictive power when genes with vastly different evolutionary rates are compared, explaining why the principle can be practically useful despite the weakness of the correlation. PMID:19132081

Robot-assisted gait training in multiple sclerosis patients: a randomized trial.

PubMed

Schwartz, Isabella; Sajin, Anna; Moreh, Elior; Fisher, Iris; Neeb, Martin; Forest, Adina; Vaknin-Dembinsky, Adi; Karusis, Dimitrios; Meiner, Zeev

2012-06-01

Preservation of locomotor activity in multiple sclerosis (MS) patients is of utmost importance. Robotic-assisted body weight-supported treadmill training is a promising method to improve gait functions in neurologically impaired patients, although its effectiveness in MS patients is still unknown. To compare the effectiveness of robot-assisted gait training (RAGT) with that of conventional walking treatment (CWT) on gait and generalized functions in a group of stable MS patients. A prospective randomized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS score 5-7. Primary outcome measures were gait parameters and the secondary outcomes were functional and quality of life parameters. All tests were performed at baseline, 3 and 6 months post-treatment by a blinded rater. Fifteen and 17 patients were randomly allocated to RAGT and CWT, respectively. Both groups were comparable at baseline in all parameters. As compared with baseline, although some gait parameters improved significantly following the treatment at each time point there was no difference between the groups. Both FIM and EDSS scores improved significantly post-treatment with no difference between the groups. At 6 months, most gait and functional parameters had returned to baseline. Robot-assisted gait training is feasible and safe and may be an effective additional therapeutic option in MS patients with severe walking disabilities.

Physiological and functional failure in chronic obstructive pulmonary disease, congestive heart failure and cancer: a debilitating intersection of sarcopenia, cachexia and breathlessness.

PubMed

Dudgeon, Deborah; Baracos, Vickie E

2016-09-01

Loss of skeletal muscle mass and cachexia are important manifestations of chronic obstructive pulmonary disease and have been associated with breathlessness, functional limitation and poor prognosis. A number of other life-limiting illnesses, including cancer and chronic heart failure as well as acute conditions seen in ICU such as sepsis, are characteristically associated with cachexia and sarcopenia. These conditions may have respiratory muscle atrophy of sufficient magnitude to contribute to the development of breathlessness and associated functional limitation. The purpose of this review is to summarize findings related to a direct role for severe respiratory muscle wasting in the etiology of breathlessness in advanced, life limiting illness. Localized wasting of respiratory muscles appears to be part of systemic wasting of skeletal muscles, driven by deconditioning, nutritional insufficiencies and inflammation, and because of disease-specific factors (tumor factors and exacerbations), anabolic insufficiency, autonomic dysfunction, drugs (such as corticosteroids and chemotherapy agents), mechanical ventilation and comorbidities. Marked morphological and biochemical abnormalities have been noted in diaphragm muscle biopsies. Older patients with multiple comorbidities associated with muscle loss and cachexia are likely to be at elevated risk of respiratory muscle atrophy and functional loss, because of the presence of multiple, interacting etiologic factors.

Emergent properties of interacting populations of spiking neurons.

PubMed

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations.

Money Management Activities in Persons With Multiple Sclerosis.

PubMed

Goverover, Yael; Haas, Shannon; DeLuca, John

2016-11-01

To examine whether participants with multiple sclerosis (MS) have more problems in managing finances compared with persons without MS, and to examine the variables that may contribute to these problems. A cross-sectional study. Nonprofit rehabilitation research institution and the community. Participants (N=53) comprised adults with MS (n=30) and persons without MS (n=23) who were recruited from a nonprofit rehabilitation research institution and from the community. Not applicable. Participants were administered a battery of neuropsychological tests, a money management survey, and a functional test to assess money management skills. Individuals with MS reported and demonstrated more problems managing money than persons without MS. Impaired cognitive functioning was significantly correlated with difficulties in money management. Self-report of functional status (Functional Behavior Profile) was significantly correlated with self-reported money management skills. To our knowledge, this is the first study to examine money management in MS. Money management is an important activity of daily living that presents problems for individuals with MS. Managing one's own money requires adequate processing speed abilities as well as executive-attentional abilities. Additional studies are needed to explore this area and understand the nature of the problem. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Biofuel combustion. Energetics and kinetics of hydrogen abstraction from carbon-1 in n-butanol by the hydroperoxyl radical calculated by coupled cluster and density functional theories and multistructural variational transition-state theory with multidimensional tunneling.

PubMed

Alecu, I M; Zheng, Jingjing; Papajak, Ewa; Yu, Tao; Truhlar, Donald G

2012-12-20

Multistructural canonical variational transition-state theory with small-curvature multidimensional tunneling (MS-CVT/SCT) is employed to calculate thermal rate constants for hydrogen-atom abstraction from carbon-1 of n-butanol by the hydroperoxyl radical over the temperature range 250-2000 K. The M08-SO hybrid meta-GGA density functional was validated against CCSD(T)-F12a explicitly correlated wave function calculations with the jul-cc-pVTZ basis set. It was then used to compute the properties of all stationary points and the energies and Hessians of a few nonstationary points along the reaction path, which were then used to generate a potential energy surface by the multiconfiguration Shepard interpolation (MCSI) method. The internal rotations in the transition state for this reaction (like those in the reactant alcohol) are strongly coupled to each other and generate multiple stable conformations, which make important contributions to the partition functions. It is shown that neglecting to account for the multiple-structure effects and torsional potential anharmonicity effects that arise from the torsional modes would lead to order-of-magnitude errors in the calculated rate constants at temperatures of interest in combustion.

Neural Plasticity in Multiple Sclerosis: The Functional and Molecular Background

PubMed Central

Glabinski, Andrzej

2015-01-01

Multiple sclerosis is an autoimmune neurodegenerative disorder resulting in motor dysfunction and cognitive decline. The inflammatory and neurodegenerative changes seen in the brains of MS patients lead to progressive disability and increasing brain atrophy. The most common type of MS is characterized by episodes of clinical exacerbations and remissions. This suggests the presence of compensating mechanisms for accumulating damage. Apart from the widely known repair mechanisms like remyelination, another important phenomenon is neuronal plasticity. Initially, neuroplasticity was connected with the developmental stages of life; however, there is now growing evidence confirming that structural and functional reorganization occurs throughout our lifetime. Several functional studies, utilizing such techniques as fMRI, TBS, or MRS, have provided valuable data about the presence of neuronal plasticity in MS patients. CNS ability to compensate for neuronal damage is most evident in RR-MS; however it has been shown that brain plasticity is also preserved in patients with substantial brain damage. Regardless of the numerous studies, the molecular background of neuronal plasticity in MS is still not well understood. Several factors, like IL-1β, BDNF, PDGF, or CB1Rs, have been implicated in functional recovery from the acute phase of MS and are thus considered as potential therapeutic targets. PMID:26229689

Emergent Properties of Interacting Populations of Spiking Neurons

PubMed Central

Cardanobile, Stefano; Rotter, Stefan

2011-01-01

Dynamic neuronal networks are a key paradigm of increasing importance in brain research, concerned with the functional analysis of biological neuronal networks and, at the same time, with the synthesis of artificial brain-like systems. In this context, neuronal network models serve as mathematical tools to understand the function of brains, but they might as well develop into future tools for enhancing certain functions of our nervous system. Here, we present and discuss our recent achievements in developing multiplicative point processes into a viable mathematical framework for spiking network modeling. The perspective is that the dynamic behavior of these neuronal networks is faithfully reflected by a set of non-linear rate equations, describing all interactions on the population level. These equations are similar in structure to Lotka-Volterra equations, well known by their use in modeling predator-prey relations in population biology, but abundant applications to economic theory have also been described. We present a number of biologically relevant examples for spiking network function, which can be studied with the help of the aforementioned correspondence between spike trains and specific systems of non-linear coupled ordinary differential equations. We claim that, enabled by the use of multiplicative point processes, we can make essential contributions to a more thorough understanding of the dynamical properties of interacting neuronal populations. PMID:22207844

Expression of CD44 3'-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis.

PubMed

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B

2011-04-01

The non-coding 3'-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3'-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3'-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3'-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3'-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed.

Expression of CD44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis

PubMed Central

Jeyapalan, Zina; Deng, Zhaoqun; Shatseva, Tatiana; Fang, Ling; He, Chengyan; Yang, Burton B.

2011-01-01

The non-coding 3′-untranslated region (UTR) plays an important role in the regulation of microRNA (miRNA) functions, since it can bind and inactivate multiple miRNAs. Here, we show the 3′-UTR of CD44 is able to antagonize cytoplasmic miRNAs, and result in the increased translation of CD44 and downstream target mRNA, CDC42. A series of cell function assays in the human breast cancer cell line, MT-1, have shown that the CD44 3′-UTR inhibits proliferation, colony formation and tumor growth. Furthermore, it modulated endothelial cell activities, favored angiogenesis, induced tumor cell apoptosis and increased sensitivity to Docetaxel. These results are due to the interaction of the CD44 3′-UTR with multiple miRNAs. Computational algorithms have predicted three miRNAs, miR-216a, miR-330 and miR-608, can bind to both the CD44 and CDC42 3′-UTRs. This was confirmed with luciferase assays, western blotting and immunohistochemical staining and correlated with a series of siRNA assays. Thus, the non-coding CD44 3′-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. PMID:21149267

Comparing phase-sensitive and phase-insensitive echolocation target images using a monaural audible sonar.

PubMed

Kuc, Roman

2018-04-01

This paper describes phase-sensitive and phase-insensitive processing of monaural echolocation waveforms to generate target maps. Composite waveforms containing both the emission and echoes are processed to estimate the target impulse response using an audible sonar. Phase-sensitive processing yields the composite signal envelope, while phase-insensitive processing that starts with the composite waveform power spectrum yields the envelope of the autocorrelation function. Analysis and experimental verification show that multiple echoes form an autocorrelation function that produces near-range phantom-reflector artifacts. These artifacts interfere with true target echoes when the first true echo occurs at a time that is less than the total duration of the target echoes. Initial comparison of phase-sensitive and phase-insensitive maps indicates that both display important target features, indicating that phase is not vital. A closer comparison illustrates the improved resolution of phase-sensitive processing, the near-range phantom-reflectors produced by phase-insensitive processing, and echo interference and multiple reflection artifacts that were independent of the processing.

Modeling Pan Evaporation for Kuwait by Multiple Linear Regression

PubMed Central

Almedeij, Jaber

2012-01-01

Evaporation is an important parameter for many projects related to hydrology and water resources systems. This paper constitutes the first study conducted in Kuwait to obtain empirical relations for the estimation of daily and monthly pan evaporation as functions of available meteorological data of temperature, relative humidity, and wind speed. The data used here for the modeling are daily measurements of substantial continuity coverage, within a period of 17 years between January 1993 and December 2009, which can be considered representative of the desert climate of the urban zone of the country. Multiple linear regression technique is used with a procedure of variable selection for fitting the best model forms. The correlations of evaporation with temperature and relative humidity are also transformed in order to linearize the existing curvilinear patterns of the data by using power and exponential functions, respectively. The evaporation models suggested with the best variable combinations were shown to produce results that are in a reasonable agreement with observation values. PMID:23226984

Object Perception Impairments Predict Instrumental Activities of Daily Living Dependence in Alzheimer's Disease

PubMed Central

JEFFERSON, ANGELA L.; BARAKAT, LAMIA P.; GIOVANNETTI, TANIA; PAUL, ROBERT H.; GLOSSER, GUILA

2009-01-01

This study examined the contribution of object perception and spatial localization to functional dependence among Alzheimer's disease (AD) patients. Forty patients with probable AD completed measures assessing verbal recognition memory, working memory, object perception, spatial localization, semantic knowledge, and global cognition. Primary caregivers completed a measure of activities of daily living (ADLs) that included instrumental and basic self-care subscales (i.e., IADLs and BADLs, respectively). Stepwise multiple regressions revealed that global cognition accounted for significant portions of variance among the ADL total, IADL, and BADL scores. However, when global cognition was removed from the model, object perception was the only significant cognitive predictor of the ADL total and IADL subscale scores, accounting for 18.5% and 19.3% of the variance, respectively. When considering multiple cognitive components simultaneously, object perception and the integrity of the inferotemporal cortex is important in the completion of functional abilities in general and IADLs in particular among AD patients. PMID:16822730

MSDB: A Comprehensive Database of Simple Sequence Repeats.

PubMed

Avvaru, Akshay Kumar; Saxena, Saketh; Sowpati, Divya Tej; Mishra, Rakesh Kumar

2017-06-01

Microsatellites, also known as Simple Sequence Repeats (SSRs), are short tandem repeats of 1-6 nt motifs present in all genomes, particularly eukaryotes. Besides their usefulness as genome markers, SSRs have been shown to perform important regulatory functions, and variations in their length at coding regions are linked to several disorders in humans. Microsatellites show a taxon-specific enrichment in eukaryotic genomes, and some may be functional. MSDB (Microsatellite Database) is a collection of >650 million SSRs from 6,893 species including Bacteria, Archaea, Fungi, Plants, and Animals. This database is by far the most exhaustive resource to access and analyze SSR data of multiple species. In addition to exploring data in a customizable tabular format, users can view and compare the data of multiple species simultaneously using our interactive plotting system. MSDB is developed using the Django framework and MySQL. It is freely available at http://tdb.ccmb.res.in/msdb. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Resilience to Meet the Challenge of Addiction

PubMed Central

Alim, Tanja N.; Lawson, William B.; Feder, Adriana; Iacoviello, Brian M.; Saxena, Shireen; Bailey, Christopher R.; Greene, Allison M.; Neumeister, Alexander

2012-01-01

Acute and chronic stress–related mechanisms play an important role in the development of addiction and its chronic, relapsing nature. Multisystem adaptations in brain, body, behavioral, and social function may contribute to a dysregulated physiological state that is maintained beyond the homeostatic range. In addition, chronic abuse of substances leads to an altered set point across multiple systems. Resilience can be defined as the absence of psychopathology despite exposure to high stress and reflects a person’s ability to cope successfully in the face of adversity, demonstrating adaptive psychological and physiological stress responses. The study of resilience can be approached by examining interindividual stress responsibility at multiple phenotypic levels, ranging from psychological differences in the way people cope with stress to differences in neurochemical or neural circuitry function. The ultimate goal of such research is the development of strategies and interventions to enhance resilience and coping in the face of stress and prevent the onset of addiction problems or relapse. PMID:23584116

Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity

PubMed Central

Herrero-Martin, Griselda; Puri, Sapna; Taketo, Makoto Mark; Rojas, Anabel; Hebrok, Matthias; Cano, David A.

2016-01-01

Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries. PMID:27736991

On the estimate of deviations of partial sums of a multiple Fourier-Walsh series of the form S2j,⋯,2jf (x ) of a function in the metric L1(Qk)

NASA Astrophysics Data System (ADS)

Igenberlina, Alua; Matin, Dauren; Turgumbayev, Mendybay

2017-09-01

In this paper, deviations of the partial sums of a multiple Fourier-Walsh series of a function in the metric L1(Qk) on a dyadic group are investigated. This estimate plays an important role in the study of equivalent normalizations in this space by means of a difference, oscillation, and best approximation by polynomials in the Walsh system. The classical classical Besov space and its equivalent normalizations are set forth in the well-known monographs of Nikolsky S.M., Besov O.V., Ilyin V.P., Triebel H.; in the works of Kazakh scientists such as Amanov T.I., Mynbaev K.T., Otelbaev M.O., Smailov E.S.. The Besov spaces on the dyadic group and the Vilenkin groups in the one-dimensional case are considered in works by Ombe H., Bloom Walter R, Fournier J., Onneweer C.W., Weyi S., Jun Tateoka.

Spectral decompositions of multiple time series: a Bayesian non-parametric approach.

PubMed

Macaro, Christian; Prado, Raquel

2014-01-01

We consider spectral decompositions of multiple time series that arise in studies where the interest lies in assessing the influence of two or more factors. We write the spectral density of each time series as a sum of the spectral densities associated to the different levels of the factors. We then use Whittle's approximation to the likelihood function and follow a Bayesian non-parametric approach to obtain posterior inference on the spectral densities based on Bernstein-Dirichlet prior distributions. The prior is strategically important as it carries identifiability conditions for the models and allows us to quantify our degree of confidence in such conditions. A Markov chain Monte Carlo (MCMC) algorithm for posterior inference within this class of frequency-domain models is presented.We illustrate the approach by analyzing simulated and real data via spectral one-way and two-way models. In particular, we present an analysis of functional magnetic resonance imaging (fMRI) brain responses measured in individuals who participated in a designed experiment to study pain perception in humans.

Development of a brain monitoring system for multimodality investigation in awake rats.

PubMed

Limnuson, Kanokwan; Narayan, Raj K; Chiluwal, Amrit; Bouton, Chad; Ping Wang; Chunyan Li

2016-08-01

Multimodal brain monitoring is an important approach to gain insight into brain function, modulation, and pathology. We have developed a unique micromachined neural probe capable of real-time continuous monitoring of multiple physiological, biochemical and electrophysiological variables. However, to date, it has only been used in anesthetized animals due to a lack of an appropriate interface for awake animals. We have developed a versatile headstage for recording the small neural signal and bridging the sensors to the remote sensing units for multimodal brain monitoring in awake rats. The developed system has been successfully validated in awake rats by simultaneously measuring four cerebral variables: electrocorticography, oxygen tension, temperature and cerebral blood flow. Reliable signal recordings were obtained with minimal artifacts from movement and environmental noise. For the first time, multiple variables of cerebral function and metabolism were simultaneously recorded from awake rats using a single neural probe. The system is envisioned for studying the effects of pharmacologic treatments, mapping the development of central nervous system diseases, and better understanding normal cerebral physiology.

A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

PubMed Central

Rand, Kristin A.; Song, Chi; Dean, Eric; Serie, Daniel J.; Curtin, Karen; Sheng, Xin; Hu, Donglei; Huff, Carol Ann; Bernal-Mizrachi, Leon; Tomasson, Michael H.; Ailawadhi, Sikander; Singhal, Seema; Pawlish, Karen; Peters, Edward S.; Bock, Cathryn H.; Stram, Alex; Van Den Berg, David J; Edlund, Christopher K.; V.Conti, David; Zimmerman, Todd; Hwang, Amie E.; Huntsman, Scott; Graff, John; Nooka, Ajay; Kong, Yinfei; Pregja, Silvana L.; Berndt, Sonja I.; Blot, William J.; Carpten, John; Casey, Graham; Chu, Lisa; Diver, W. Ryan; Stevens, Victoria L.; Lieber, Michael R.; Goodman, Phyllis J.; Hennis, Anselm J.M.; Hsing, Ann W.; Mehta, Jayesh; Kittles, Rick A.; Kolb, Suzanne; Klein, Eric A.; Leske, Cristina; Murphy, Adam B.; Nemesure, Barbara; Neslund-Dudas, Christine; Strom, Sara S.; Vij, Ravi; Rybicki, Benjamin A.; Stanford, Janet L.; Signorello, Lisa B.; Witte, John S.; Ambrosone, Christine B.; Bhatti, Parveen; John, Esther M.; Bernstein, Leslie; Zheng, Wei; Olshan, Andrew F.; Hu, Jennifer J.; Ziegler, Regina G.; Nyante, Sarah J.; Bandera, Elisa V.; Birmann, Brenda M.; Ingles, Sue A.; Press, Michael F.; Atanackovic, Djordje; Glenn, Martha J.; Cannon-Albright, Lisa A.; Jones, Brandt; Tricot, Guido; Martin, Thomas G.; Kumar, Shaji K.; Wolf, Jeffrey L.; Deming, Sandra L.; Rothman, Nathaniel; Brooks-Wilson, Angela R.; Rajkumar, S. Vincent; Kolonel, Laurence N.; Chanock, Stephen J.; Slager, Susan L.; Severson, Richard K.; Janakiraman, Nalini; Terebelo, Howard R.; Brown, Elizabeth E.; De Roos, Anneclaire J.; Mohrbacher, Ann F.; Colditz, Graham A.; Giles, Graham G.; Spinelli, John J.; Chiu, Brian C.; Munshi, Nikhil C.; Anderson, Kenneth C.; Levy, Joan; Zonder, Jeffrey A.; Orlowski, Robert Z.; Lonial, Sagar; Camp, Nicola J.; Vachon, Celine M.; Ziv, Elad; Stram, Daniel O.; Hazelett, Dennis J.; Haiman, Christopher A.; Cozen, Wendy

2017-01-01

Background Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM). Methods We performed association testing of common variation in eight regions in 1,264 MM patients and 1,479 controls of European ancestry (EA) and 1,305 MM patients and 7,078 controls of African ancestry (AA) and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. Results We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (p<0.05) associated with MM risk in AAs and EAs and the variant in 3p22.1 was associated in EAs only. In a combined AA-EA meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically signficantly associated with MM risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 3′ end of the CDCA7L transcription termination site. A missense variant at 17p11.2 (rs34562254, Pro251Leu, OR=1.32, p=2.93×10−7) in TNFRSF13B, encodes a lymphocyte-specific protein in the tumor necrosis factor receptor family that interacts with the NF-κB pathway. SNPs correlated with the index signal in 22q13.1 cluster around the promoter and enhancer regions of CBX7. Conclusions We found that reported MM susceptibility regions contain risk variants important across populations supporting the use of multiple racial/ethnic groups with different underlying genetic architecture to enhance the localization and identification of putatively functional alleles. Impact A subset of reported risk loci for multiple myeloma have consistent affects across populations and are likely to be functional. PMID:27587788

New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies

NASA Astrophysics Data System (ADS)

Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J.; Gu, Baohua; Roeder, Ryan K.; Wang, Wei; Retterer, Scott T.

2015-04-01

Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 +/- 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg-1 of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials.Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 +/- 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg-1 of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach described here is applicable to the synthesis of a large class of nanomaterials with multiple core and surface functionalities. This work combined with the biodistribution data suggests that the radiolabeling schemes carried out in this study have broad implications for use in pharmacokinetic studies for a variety of nanomaterials. Electronic supplementary information (ESI) available: (S1) High-Resolution Transmission Electron Microscopy (HRTEM) image of iron oxide nanoparticles, (S2) Superconducting Quantum Interference Device (SQUID) measurement of magnetization of super paramagnetic iron oxide nanoparticles, (S3) Fourier Transform Infrared Spectroscopy (FT-IR) spectra of Fe-Si-COO- synthesised using Grignard reagents (S4) FT-IR spectra of iron oxide nanoparticles silanized with commercially available N-[(3-Trimethoxysilyl)propyl]ethylenediamine triacetic acid tripotassium salt, (S5) Synthesis of hyperbranched amine functionalized iron oxide nanoparticles from amino propyl triethyl silane functionalized iron nanoparticles using ethyleneimine as an initiator and polymerizing agent. See DOI: 10.1039/c4nr06441k

Human factors considerations for training astronauts to function effectively in multiple environments

NASA Technical Reports Server (NTRS)

Cohen, Malcolm M.

1991-01-01

This paper reviews some of the basic issues involved in training individuals to function appropriately under the several conditions that comprise the aerospace environment. The topic of transfer of training is examined in some detail, and the use of high-fidelity simulators in various training programs is discussed. Both current and classical techniques used to train astronauts are noted, and some relatively new and innovative training techniques and methods are described. Particularly, the paper discusses an important aspect of functioning appropriately in a given environment that is based on how well the operator calibrates his motor activity for that specific environment. The role of motor-sensory feedback for the acquisition of motor skills is discussed in the context of training.

Testing Associations of Plant Functional Diversity with Carbon and Nitrogen Storage along a Restoration Gradient of Sandy Grassland

PubMed Central

Zuo, Xiaoan; Zhou, Xin; Lv, Peng; Zhao, Xueyong; Zhang, Jing; Wang, Shaokun; Yue, Xiyuan

2016-01-01

The trait-based approach shows that ecosystem function is strongly affected by plant functional diversity as reflected by the traits of the most abundant species (community-weighted mean, CWM) and functional dispersion (FDis). Effects of CWM and FDis individually support the biomass ratio hypothesis and the niche complementarity hypothesis. However, there is little empirical evidence on the relative roles of CWM traits and FDis in explaining the carbon (C) and nitrogen (N) storage in grassland ecosystems. We measured plant functional traits in the 34 most abundant species across 24 sites along a restoration gradient of sandy grassland (mobile dune, semi-fixed dune, fixed dune, and grassland) in Horqin Sand Land, northern China. Thereafter, we calculated the CWM traits, the functional divergence of each single trait (FDvar) and the trait dispersion of multiple traits (FDis). We also measured the C and N storage in plant, litter, root, and soil. Using a stepwise multiple regression analysis, we further assessed which of the functional diversity components best explained C and N storage in the sandy grassland restoration. We found consistent links between C or N storage and leaf traits related to plant resource use strategy. However, the CWM of plant height was retained as an important predictor of C and N storage in plant, litter, soil, and total ecosystem in the final multiple models. CWMs of specific leaf area and plant height best predicted soil C and N storage and total ecosystem N storage. FDis was one of good predictors of litter C and N storage as well as total ecosystem C storage. These results suggest that ecosystem C and N pools in the sandy grassland restoration are primarily associated with the traits of the most abundant species in communities, thereby supporting the biomass ratio hypothesis. The positive associations of FDis with C storage in litter and total ecosystem provide evidence to support the niche complementarity hypothesis. Both functional traits of dominant species and traits’ dispersion in plant communities could contribute to explaining total ecosystem C storage. Thus, single- and multi-trait indices of functional composition play a crucial role in predicting C storage in sandy grasslands. PMID:26925089

Multiple Resting-State Networks Are Associated With Tremors and Cognitive Features in Essential Tremor.

PubMed

Fang, Weidong; Chen, Huiyue; Wang, Hansheng; Zhang, Han; Liu, Mengqi; Puneet, Munankami; Lv, Fajin; Cheng, Oumei; Wang, Xuefeng; Lu, Xiurong; Luo, Tianyou

2015-12-01

The heterogeneous clinical features of essential tremor indicate that the dysfunctions of this syndrome are not confined to motor networks, but extend to nonmotor networks. Currently, these neural network dysfunctions in essential tremor remain unclear. In this study, independent component analysis of resting-state functional MRI was used to study these neural network mechanisms. Thirty-five essential tremor patients and 35 matched healthy controls with clinical and neuropsychological tests were included, and eight resting-state networks were identified. After considering the structure and head-motion factors and testing the reliability of the selected resting-state networks, we assessed the functional connectivity changes within or between resting-state networks. Finally, image-behavior correlation analysis was performed. Compared to healthy controls, essential tremor patients displayed increased functional connectivity in the sensorimotor and salience networks and decreased functional connectivity in the cerebellum network. Additionally, increased functional network connectivity was observed between anterior and posterior default mode networks, and a decreased functional network connectivity was noted between the cerebellum network and the sensorimotor and posterior default mode networks. Importantly, the functional connectivity changes within and between these resting-state networks were correlated with the tremor severity and total cognitive scores of essential tremor patients. The findings of this study provide the first evidence that functional connectivity changes within and between multiple resting-state networks are associated with tremors and cognitive features of essential tremor, and this work demonstrates a potential approach for identifying the underlying neural network mechanisms of this syndrome. © 2015 International Parkinson and Movement Disorder Society.

Global sensitivity analysis for identifying important parameters of nitrogen nitrification and denitrification under model uncertainty and scenario uncertainty

NASA Astrophysics Data System (ADS)

Chen, Zhuowei; Shi, Liangsheng; Ye, Ming; Zhu, Yan; Yang, Jinzhong

2018-06-01

Nitrogen reactive transport modeling is subject to uncertainty in model parameters, structures, and scenarios. By using a new variance-based global sensitivity analysis method, this paper identifies important parameters for nitrogen reactive transport with simultaneous consideration of these three uncertainties. A combination of three scenarios of soil temperature and two scenarios of soil moisture creates a total of six scenarios. Four alternative models describing the effect of soil temperature and moisture content are used to evaluate the reduction functions used for calculating actual reaction rates. The results show that for nitrogen reactive transport problem, parameter importance varies substantially among different models and scenarios. Denitrification and nitrification process is sensitive to soil moisture content status rather than to the moisture function parameter. Nitrification process becomes more important at low moisture content and low temperature. However, the changing importance of nitrification activity with respect to temperature change highly relies on the selected model. Model-averaging is suggested to assess the nitrification (or denitrification) contribution by reducing the possible model error. Despite the introduction of biochemical heterogeneity or not, fairly consistent parameter importance rank is obtained in this study: optimal denitrification rate (Kden) is the most important parameter; reference temperature (Tr) is more important than temperature coefficient (Q10); empirical constant in moisture response function (m) is the least important one. Vertical distribution of soil moisture but not temperature plays predominant role controlling nitrogen reaction. This study provides insight into the nitrogen reactive transport modeling and demonstrates an effective strategy of selecting the important parameters when future temperature and soil moisture carry uncertainties or when modelers face with multiple ways of establishing nitrogen models.

Salivary gland ultrasonography as a primary imaging tool for predicting efficacy of xerostomia treatment in patients with Sjögren's syndrome.

PubMed

Takagi, Yukinori; Sumi, Misa; Nakamura, Hideki; Sato, Shuntaro; Kawakami, Atsushi; Nakamura, Takashi

2016-02-01

To evaluate ultrasonography (US) grading of salivary gland disease as a predictor of treatment efficacy for impaired salivary function in xerostomia patients with or without Sjögren's syndrome (SS). We retrospectively analysed the prognostic importance of salivary US grading in 317 patients (168 with SS and 149 without SS). US images of the parotid and submandibular glands in each patient were individually categorized into grades 0-4 based on the extent of damage to the gland; and the sum total grade of the two gland types on either side was assigned a US score of 0-8 for each patient. The relative importance of US score and demographic and clinical variables was assessed using stepwise multiple regression analysis after various durations of xerostomia treatment. Multiple regression analysis indicated that the baseline US score before treatment was the most important factor [standardized regression coefficient (β) = -0.523, t-statistic (t) = -7.967, P < 0.001] in predicting negative outcomes in SS patients. Treatment duration (β = 0.277, t = 4.225, P < 0.001) was also a significant but less important positive variable. On the other hand, US grading did not effectively predict treatment outcomes in non-SS patients, with treatment duration (β = 0.199, t = 2.486, P = 0.014) and baseline salivary flow rate before treatment (β = -0.172, t = -2.159, P = 0.032) being significant but weak predictors of positive and negative outcome, respectively. Salivary gland US grading may help to predict outcomes of treatment for impaired salivary function in patients with SS. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Statistical technique for analysing functional connectivity of multiple spike trains.

PubMed

Masud, Mohammad Shahed; Borisyuk, Roman

2011-03-15

A new statistical technique, the Cox method, used for analysing functional connectivity of simultaneously recorded multiple spike trains is presented. This method is based on the theory of modulated renewal processes and it estimates a vector of influence strengths from multiple spike trains (called reference trains) to the selected (target) spike train. Selecting another target spike train and repeating the calculation of the influence strengths from the reference spike trains enables researchers to find all functional connections among multiple spike trains. In order to study functional connectivity an "influence function" is identified. This function recognises the specificity of neuronal interactions and reflects the dynamics of postsynaptic potential. In comparison to existing techniques, the Cox method has the following advantages: it does not use bins (binless method); it is applicable to cases where the sample size is small; it is sufficiently sensitive such that it estimates weak influences; it supports the simultaneous analysis of multiple influences; it is able to identify a correct connectivity scheme in difficult cases of "common source" or "indirect" connectivity. The Cox method has been thoroughly tested using multiple sets of data generated by the neural network model of the leaky integrate and fire neurons with a prescribed architecture of connections. The results suggest that this method is highly successful for analysing functional connectivity of simultaneously recorded multiple spike trains. Copyright © 2011 Elsevier B.V. All rights reserved.

Increased Range of Motion Is Important for Functional Outcome and Satisfaction After Total Knee Arthroplasty in Asian Patients.

PubMed

Ha, Chul-Won; Park, Yong-Beom; Song, Young-Suk; Kim, Jun-Ho; Park, Yong-Geun

2016-06-01

Although range of motion (ROM) is considered as an important factor for good outcome after total knee arthroplasty (TKA), the association of the degree of ROM with functional outcome and patient satisfaction is debated. We, therefore, investigated whether increased ROM would affect functional outcome and patient satisfaction after TKA in Asian patients. We reviewed 630 patients who underwent primary TKA with minimum 2-year follow-up. Clinical outcomes were evaluated by Knee Society (KS) score, Western Ontario and McMaster Universities osteoarthritis index, and high-flexion knee score. Patient satisfaction was evaluated using a validated questionnaire. The association of ROM and change in ROM (cROM) with clinical outcomes and satisfaction were analyzed using partial correlation analysis and multiple median regression analysis. All functional scores showed significant correlation with postoperative ROM (r = 0.129, P = .001 in Knee Society score; r = -0.101, P = .012 in Western Ontario and McMaster Universities osteoarthritis index; r = 0.183, P < .001 in high-flexion knee score). cROM correlated with satisfaction (r = 0.192, P = .005). Postoperative ROM and cROM were revealed as predisposing factors affecting function outcome using multivariable regression analysis. cROM was found as a predisposing factor affecting satisfaction. Based on the results of this study, ROM positively associated with functional outcome and cROM positively associated with patient satisfaction after TKA. These findings suggest that increased ROM after TKA is an important factor for functional outcome and satisfaction in Asian patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction.

PubMed

Podlasek, Carol A; Mulhall, John; Davies, Kelvin; Wingard, Christopher J; Hannan, Johanna L; Bivalacqua, Trinity J; Musicki, Biljana; Khera, Mohit; González-Cadavid, Nestor F; Burnett, Arthur L

2016-08-01

The biological importance of testosterone is generally accepted by the medical community; however, controversy focuses on its relevance to sexual function and the sexual response, and our understanding of the extent of its role in this area is evolving. To provide scientific evidence examining the role of testosterone at the cellular and molecular levels as it pertains to normal erectile physiology and the development of erectile dysfunction and to assist in guiding successful therapeutic interventions for androgen-dependent sexual dysfunction. In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current basic science literature examining the role of testosterone in sexual function and dysfunction. Testosterone plays an important role in sexual function through multiple processes: physiologic (stimulates activity of nitric oxide synthase), developmental (establishes and maintains the structural and functional integrity of the penis), neural (development, maintenance, function, and plasticity of the cavernous nerve and pelvic ganglia), therapeutically for dysfunctional regulation (beneficial effect on aging, diabetes, and prostatectomy), and phosphodiesterase type 5 inhibition (testosterone supplement to counteract phosphodiesterase type 5 inhibitor resistance). Despite controversies concerning testosterone with regard to sexual function, basic science studies provide incontrovertible evidence for a significant role of testosterone in sexual function and suggest that properly administered testosterone therapy is potentially advantageous for treating male sexual dysfunction. Published by Elsevier Inc.

A qualitative analysis of adolescent, caregiver, and clinician perceptions of the impact of migraines on adolescents' social functioning.

PubMed

Donovan, Elizabeth; Mehringer, Stacey; Zeltzer, Lonnie K

2013-12-01

Migraines dramatically affect adolescents' quality of life. One area of particular importance is the impact of migraines on adolescents' social functioning. To understand the impact of migraines on adolescents' social functioning from multiple informants, we performed semistructured interviews with adolescents who have migraines, their caregivers, and clinicians who treat adolescents who have migraines. Three major themes related to social functioning were identified from the adolescent interviews: The need to be alone; lack of support from siblings; and the feeling of not being understood by others. The caregiver interviews yielded three main themes related to family functioning: that plans can change quickly; that family life revolves around helping the child with the migraine; and parents' feelings of inadequacy in helping their child. There were two main themes derived from the clinician interviews related to perception of family functioning: the importance of parental involvement; and the role of adolescents' school and social lives in migraine prevention. There are a number of unmet needs among adolescents with recurrent migraine and their families. Interviews with adolescents, caregivers, and clinicians suggest a number of areas for intervention. Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

GeneSCF: a real-time based functional enrichment tool with support for multiple organisms.

PubMed

Subhash, Santhilal; Kanduri, Chandrasekhar

2016-09-13

High-throughput technologies such as ChIP-sequencing, RNA-sequencing, DNA sequencing and quantitative metabolomics generate a huge volume of data. Researchers often rely on functional enrichment tools to interpret the biological significance of the affected genes from these high-throughput studies. However, currently available functional enrichment tools need to be updated frequently to adapt to new entries from the functional database repositories. Hence there is a need for a simplified tool that can perform functional enrichment analysis by using updated information directly from the source databases such as KEGG, Reactome or Gene Ontology etc. In this study, we focused on designing a command-line tool called GeneSCF (Gene Set Clustering based on Functional annotations), that can predict the functionally relevant biological information for a set of genes in a real-time updated manner. It is designed to handle information from more than 4000 organisms from freely available prominent functional databases like KEGG, Reactome and Gene Ontology. We successfully employed our tool on two of published datasets to predict the biologically relevant functional information. The core features of this tool were tested on Linux machines without the need for installation of more dependencies. GeneSCF is more reliable compared to other enrichment tools because of its ability to use reference functional databases in real-time to perform enrichment analysis. It is an easy-to-integrate tool with other pipelines available for downstream analysis of high-throughput data. More importantly, GeneSCF can run multiple gene lists simultaneously on different organisms thereby saving time for the users. Since the tool is designed to be ready-to-use, there is no need for any complex compilation and installation procedures.

Family Functioning and Dysfunctional Eating Among Italian Adolescents: The Moderating Role of Gender.

PubMed

Laghi, Fiorenzo; McPhie, Meghan L; Baumgartner, Emma; Rawana, Jennine S; Pompili, Sara; Baiocco, Roberto

2016-02-01

The first aim of this study was to examine the association between different dimensions of family functioning and dysfunctional eating in a sample of Italian adolescent boys and girls. The second aim was to investigate whether gender moderates the relationship between family functioning and dysfunctional eating. Seven hundred and twenty seven adolescents (500 boys and 227 girls) with ages ranging from 15 to 18 years completed a survey of self-report measures. Findings from hierarchical multiple regression analysis suggested that aspects of family functioning such as flexibility, cohesion, disengagement, enmeshment, rigidity and chaotic were related to dysfunctional eating in adolescents. Additionally the results indicated differences between boys and girls, in particular dysfunctional eating in adolescent boys seemed to be more affected by dimensions of enmeshment and disengagement than dysfunctional eating in girls. This research highlights the important role of various aspects of family functioning in relation to dysfunctional eating in adolescents.

The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity

PubMed Central

Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.

2012-01-01

The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406

Endoreplication and polyploidy: insights into development and disease

PubMed Central

Fox, Donald T.; Duronio, Robert J.

2013-01-01

Polyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that control the generation of polyploidy and have recently begun to provide clues to its physiological function. These studies demonstrate that cellular polyploidy plays important roles during normal development and also contributes to human disease, particularly cancer. PMID:23222436

Nanometric summation architecture based on optical near-field interaction between quantum dots.

PubMed

Naruse, Makoto; Miyazaki, Tetsuya; Kubota, Fumito; Kawazoe, Tadashi; Kobayashi, Kiyoshi; Sangu, Suguru; Ohtsu, Motoichi

2005-01-15

A nanoscale data summation architecture is proposed and experimentally demonstrated based on the optical near-field interaction between quantum dots. Based on local electromagnetic interactions between a few nanometric elements via optical near fields, we can combine multiple excitations at a certain quantum dot, which allows construction of a summation architecture. Summation plays a key role for content-addressable memory, which is one of the most important functions in optical networks.

Sampled-Data Kalman Filtering and Multiple Model Adaptive Estimation for Infinite-Dimensional Continuous-Time Systems

DTIC Science & Technology

2007-03-01

mathematical frame- 1-6 work of linear algebra and functional analysis [122, 33], while Kalman-Bucy filtering [96, 32] is an especially important...Engineering, Air Force Institute of Technology (AU), Wright- Patterson AFB, Ohio, March 2002. 85. Hoffman, Kenneth and Ray Kunze. Linear Algebra (Second Edition...Engineering, Air Force Institute of Technology (AU), Wright- Patterson AFB, Ohio, December 1989. 189. Strang, Gilbert. Linear Algebra and Its Applications

Percolation galaxy groups and clusters in the sdss redshift survey: identification, catalogs, and the multiplicity function

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

Berlind, Andreas A.; Frieman, Joshua A.; Weinberg, David H.

2006-01-01

We identify galaxy groups and clusters in volume-limited samples of the SDSS redshift survey, using a redshift-space friends-of-friends algorithm. We optimize the friends-of-friends linking lengths to recover galaxy systems that occupy the same dark matter halos, using a set of mock catalogs created by populating halos of N-body simulations with galaxies. Extensive tests with these mock catalogs show that no combination of perpendicular and line-of-sight linking lengths is able to yield groups and clusters that simultaneously recover the true halo multiplicity function, projected size distribution, and velocity dispersion. We adopt a linking length combination that yields, for galaxy groups withmore » ten or more members: a group multiplicity function that is unbiased with respect to the true halo multiplicity function; an unbiased median relation between the multiplicities of groups and their associated halos; a spurious group fraction of less than {approx}1%; a halo completeness of more than {approx}97%; the correct projected size distribution as a function of multiplicity; and a velocity dispersion distribution that is {approx}20% too low at all multiplicities. These results hold over a range of mock catalogs that use different input recipes of populating halos with galaxies. We apply our group-finding algorithm to the SDSS data and obtain three group and cluster catalogs for three volume-limited samples that cover 3495.1 square degrees on the sky. We correct for incompleteness caused by fiber collisions and survey edges, and obtain measurements of the group multiplicity function, with errors calculated from realistic mock catalogs. These multiplicity function measurements provide a key constraint on the relation between galaxy populations and dark matter halos.« less

Multiple Ion Binding Equilibria, Reaction Kinetics, and Thermodynamics in Dynamic Models of Biochemical Pathways

PubMed Central

Vinnakota, Kalyan C.; Wu, Fan; Kushmerick, Martin J.; Beard, Daniel A.

2009-01-01

The operation of biochemical systems in vivo and in vitro is strongly influenced by complex interactions between biochemical reactants and ions such as H+, Mg2+, K+, and Ca2+. These are important second messengers in metabolic and signaling pathways that directly influence the kinetics and thermodynamics of biochemical systems. Herein we describe the biophysical theory and computational methods to account for multiple ion binding to biochemical reactants and demonstrate the crucial effects of ion binding on biochemical reaction kinetics and thermodynamics. In simulations of realistic systems, the concentrations of these ions change with time due to dynamic buffering and competitive binding. In turn, the effective thermodynamic properties vary as functions of cation concentrations and important environmental variables such as temperature and overall ionic strength. Physically realistic simulations of biochemical systems require incorporating all of these phenomena into a coherent mathematical description. Several applications to physiological systems are demonstrated based on this coherent simulation framework. PMID:19216922

The metabolic enzyme fructose-1,6-bisphosphate aldolase acts as a transcriptional regulator in pathogenic Francisella.

PubMed

Ziveri, Jason; Tros, Fabiola; Guerrera, Ida Chiara; Chhuon, Cerina; Audry, Mathilde; Dupuis, Marion; Barel, Monique; Korniotis, Sarantis; Fillatreau, Simon; Gales, Lara; Cahoreau, Edern; Charbit, Alain

2017-10-11

The enzyme fructose-bisphosphate aldolase occupies a central position in glycolysis and gluconeogenesis pathways. Beyond its housekeeping role in metabolism, fructose-bisphosphate aldolase has been involved in additional functions and is considered as a potential target for drug development against pathogenic bacteria. Here, we address the role of fructose-bisphosphate aldolase in the bacterial pathogen Francisella novicida. We demonstrate that fructose-bisphosphate aldolase is important for bacterial multiplication in macrophages in the presence of gluconeogenic substrates. In addition, we unravel a direct role of this metabolic enzyme in transcription regulation of genes katG and rpoA, encoding catalase and an RNA polymerase subunit, respectively. We propose a model in which fructose-bisphosphate aldolase participates in the control of host redox homeostasis and the inflammatory immune response.The enzyme fructose-bisphosphate aldolase (FBA) plays central roles in glycolysis and gluconeogenesis. Here, Ziveri et al. show that FBA of the pathogen Francisella novicida acts, in addition, as a transcriptional regulator and is important for bacterial multiplication in macrophages.

Validity, invariance and responsiveness of a self-report measure of functional limitations and disability in multiple sclerosis.

PubMed

Motl, Robert W; McAuley, Edward; Suh, Yoojin

2010-01-01

This study examined the structural and external aspects of score validity for the abbreviated Late Life-Function and Disability Inventory (LL-FDI) as well as its longitudinal measurement invariance and responsiveness in individuals with multiple sclerosis (MS). The sample included 292 individuals with MS who completed a battery of questionnaires on two occasions separated by 6 months. The battery included the abbreviated LL-FDI along with measures of mobility disability; neurological impairments; symptoms of fatigue, anxiety, depression and pain; health status; and quality of life. The data were analysed using Analysis of Moment Structures (AMOS) and Statistical Package for the Social Sciences (SPSS), versions 16.0. Confirmatory factor analysis supported the structural validity and longitudinal measurement invariance of the disability and functional limitations components of the abbreviated LL-FDI. MANOVA and bivariate correlations supported the external aspects of score validity based on differences in mean scores as a function of clinical MS course (relapsing vs. progressive) and level of mobility disability (mild vs. moderate mobility disability) and associations with measures of neurological impairments, symptoms, health status and QOL, respectively. ANOVA established the responsiveness (i.e., sensitivity for reflecting clinically important differences in health status across time) of the functional limitations and disability components of the abbreviated LL-FDI for detecting changes in mobility disability across 6-months. Such findings provide a new option for the measurement of functional limitations and disability using the abbreviated LL-FDI in persons with MS.

Genome-wide co-localization of Polycomb orthologs and their effects on gene expression in human fibroblasts

PubMed Central

2014-01-01

Background Polycomb group proteins form multicomponent complexes that are important for establishing lineage-specific patterns of gene expression. Mammalian cells encode multiple permutations of the prototypic Polycomb repressive complex 1 (PRC1) with little evidence for functional specialization. An aim of this study is to determine whether the multiple orthologs that are co-expressed in human fibroblasts act on different target genes and whether their genomic location changes during cellular senescence. Results Deep sequencing of chromatin immunoprecipitated with antibodies against CBX6, CBX7, CBX8, RING1 and RING2 reveals that the orthologs co-localize at multiple sites. PCR-based validation at representative loci suggests that a further six PRC1 proteins have similar binding patterns. Importantly, sequential chromatin immunoprecipitation with antibodies against different orthologs implies that multiple variants of PRC1 associate with the same DNA. At many loci, the binding profiles have a distinctive architecture that is preserved in two different types of fibroblast. Conversely, there are several hundred loci at which PRC1 binding is cell type-specific and, contrary to expectations, the presence of PRC1 does not necessarily equate with transcriptional silencing. Interestingly, the PRC1 binding profiles are preserved in senescent cells despite changes in gene expression. Conclusions The multiple permutations of PRC1 in human fibroblasts congregate at common rather than specific sites in the genome and with overlapping but distinctive binding profiles in different fibroblasts. The data imply that the effects of PRC1 complexes on gene expression are more subtle than simply repressing the loci at which they bind. PMID:24485159

The Cultural Adaptability of Intermediate Measures of Functional Outcome in Schizophrenia*

PubMed Central

Rubin, Maureen; Fredrick, Megan M.; Mintz, Jim; Nuechterlein, Keith H.; Schooler, Nina R.; Jaeger, Judith; Peters, Nancy M.; Buller, Raimund; Marder, Stephen R.; Dube, Sanjay

2012-01-01

The Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative was designed to encourage the development of cognitive enhancing agents for schizophrenia. For a medication to receive this indication, regulatory agencies require evidence of improvement in both cognition and functional outcome. Because medication trials are conducted across multiple countries, we examined ratings of the cross-cultural adaptability of 4 intermediate measures of functional outcome (Independent Living Scales, UCSD Performance-based Skills Assessment, Test of Adaptive Behavior in Schizophrenia, Cognitive Assessment Interview [CAI]) made by experienced clinical researchers at 31 sites in 8 countries. English-speaking research staff familiar with conducting medication trials rated the extent to which each subscale of each intermediate measure could be applied to their culture and to subgroups within their culture based on gender, geographic region, ethnicity, and socioeconomic status on the Cultural Adaptation Rating Scale. Ratings suggested that the CAI would be easiest to adapt across cultures. However, in a recent study, the CAI was found to have weaker psychometric properties than some of the other measures. Problems were identified for specific subscales on all the performance-based assessments across multiple countries. India, China, and Mexico presented the greatest challenges in adaptation. For international clinical trials, it would be important to use the measures that are most adaptable, to adapt subscales that are problematic for specific countries or regions, or to develop a battery composed of the subscales from different instruments that may be most acceptable across multiple cultures with minimal adaptation. PMID:21134973

The role of the host in a cooperating mainframe and workstation environment, volumes 1 and 2

NASA Technical Reports Server (NTRS)

Kusmanoff, Antone; Martin, Nancy L.

1989-01-01

In recent years, advancements made in computer systems have prompted a move from centralized computing based on timesharing a large mainframe computer to distributed computing based on a connected set of engineering workstations. A major factor in this advancement is the increased performance and lower cost of engineering workstations. The shift to distributed computing from centralized computing has led to challenges associated with the residency of application programs within the system. In a combined system of multiple engineering workstations attached to a mainframe host, the question arises as to how does a system designer assign applications between the larger mainframe host and the smaller, yet powerful, workstation. The concepts related to real time data processing are analyzed and systems are displayed which use a host mainframe and a number of engineering workstations interconnected by a local area network. In most cases, distributed systems can be classified as having a single function or multiple functions and as executing programs in real time or nonreal time. In a system of multiple computers, the degree of autonomy of the computers is important; a system with one master control computer generally differs in reliability, performance, and complexity from a system in which all computers share the control. This research is concerned with generating general criteria principles for software residency decisions (host or workstation) for a diverse yet coupled group of users (the clustered workstations) which may need the use of a shared resource (the mainframe) to perform their functions.

Encoding Time in Feedforward Trajectories of a Recurrent Neural Network Model.

PubMed

Hardy, N F; Buonomano, Dean V

2018-02-01

Brain activity evolves through time, creating trajectories of activity that underlie sensorimotor processing, behavior, and learning and memory. Therefore, understanding the temporal nature of neural dynamics is essential to understanding brain function and behavior. In vivo studies have demonstrated that sequential transient activation of neurons can encode time. However, it remains unclear whether these patterns emerge from feedforward network architectures or from recurrent networks and, furthermore, what role network structure plays in timing. We address these issues using a recurrent neural network (RNN) model with distinct populations of excitatory and inhibitory units. Consistent with experimental data, a single RNN could autonomously produce multiple functionally feedforward trajectories, thus potentially encoding multiple timed motor patterns lasting up to several seconds. Importantly, the model accounted for Weber's law, a hallmark of timing behavior. Analysis of network connectivity revealed that efficiency-a measure of network interconnectedness-decreased as the number of stored trajectories increased. Additionally, the balance of excitation (E) and inhibition (I) shifted toward excitation during each unit's activation time, generating the prediction that observed sequential activity relies on dynamic control of the E/I balance. Our results establish for the first time that the same RNN can generate multiple functionally feedforward patterns of activity as a result of dynamic shifts in the E/I balance imposed by the connectome of the RNN. We conclude that recurrent network architectures account for sequential neural activity, as well as for a fundamental signature of timing behavior: Weber's law.

Maternally derived trypsin may have multiple functions in the early development of turbot (Scopthalmus maximus).

PubMed

Chi, Liang; Liu, Qinghua; Xu, Shihong; Xiao, Zhizhong; Ma, Daoyuan; Li, Jun

2015-10-01

Trypsin is an important serine protease that is considered to be involved in digestion of protein in teleost fish. Nevertheless, studies on trypsin/trypsinogen in fish embryos are very limited. In this study, the trypsinogen of turbot (Scophthalmus maximus) (tTG) was identified and the expression patterns and activity of trypsinogen/trypsin were investigated. The results showed that the tTG mRNA was evenly distributed in the oocytes and was also expressed along the yolk periphery in early embryos. At later embryo stages and 1 days after hatching (dph), the tTG mRNA concentrated at the alimentary tract and head. Quantitative expression analysis showed that the tTG transcripts decreased after fertilization until the gastrula stage, then increased with the embryo and larvae development. This result was also confirmed by the specific activity analysis of trypsin and in-situ-hybridization (ISH). All of the results indicated that tTG in early embryo stages was maternally derived and expressed by itself after gastrula stages. Additionally, location of tTG mRNA in embryos and larvae was investigated; we considered that trypsin may have multiple functions during the embryo development process. Based on our results regarding trypsinogen in embryos and early development, we concluded that the trypsin/trypsinogen in turbot embryos was inherited from a maternal source and we suggested that trypsin in early development has multiple functions in the process of development. Copyright © 2015 Elsevier Inc. All rights reserved.

Robust biological parametric mapping: an improved technique for multimodal brain image analysis

NASA Astrophysics Data System (ADS)

Yang, Xue; Beason-Held, Lori; Resnick, Susan M.; Landman, Bennett A.

2011-03-01

Mapping the quantitative relationship between structure and function in the human brain is an important and challenging problem. Numerous volumetric, surface, region of interest and voxelwise image processing techniques have been developed to statistically assess potential correlations between imaging and non-imaging metrics. Recently, biological parametric mapping has extended the widely popular statistical parametric approach to enable application of the general linear model to multiple image modalities (both for regressors and regressands) along with scalar valued observations. This approach offers great promise for direct, voxelwise assessment of structural and functional relationships with multiple imaging modalities. However, as presented, the biological parametric mapping approach is not robust to outliers and may lead to invalid inferences (e.g., artifactual low p-values) due to slight mis-registration or variation in anatomy between subjects. To enable widespread application of this approach, we introduce robust regression and robust inference in the neuroimaging context of application of the general linear model. Through simulation and empirical studies, we demonstrate that our robust approach reduces sensitivity to outliers without substantial degradation in power. The robust approach and associated software package provides a reliable way to quantitatively assess voxelwise correlations between structural and functional neuroimaging modalities.

Direct Evidence for the Formation of Diastereoisomeric Benzylpenicilloyl Haptens from Benzylpenicillin and Benzylpenicillenic Acid in PatientsS⃞

PubMed Central

Meng, Xiaoli; Jenkins, Rosalind E.; Berry, Neil G.; Maggs, James L.; Farrell, John; Lane, Catherine S.; Stachulski, Andrew V.; French, Neil S.; Naisbitt, Dean J.; Pirmohamed, Munir

2011-01-01

Covalent binding to proteins to form neoantigens is thought to be central to the pathogenesis of penicillin hypersensitivity reactions. We have undertaken detailed mass spectrometric studies to define the mechanism and protein chemistry of hapten formation from benzylpenicillin (BP) and its rearrangement product, benzylpenicillenic acid (PA). Mass spectrometric analysis of human serum albumin exposed to BP and PA in vitro revealed that at low concentrations (drug protein molar ratio 0.001:1) and during short time incubations BP and PA selectively target different residues, Lys199 and Lys525, respectively. Molecular modeling showed that the selectivity was a function of noncovalent interaction before covalent modification. With increased exposure to higher concentrations of BP and PA, multiple epitopes were detected on albumin, demonstrating that the multiplicity of hapten formation is a function of time and concentration. More importantly, we have demonstrated direct evidence that PA is a hapten accounting for the diastereoisomeric BP antigen formation in albumin isolated from the blood of patients receiving penicillin. Furthermore, PA was found to be more potent than BP with respect to stimulation of T cells from patients with penicillin hypersensitivity, illustrating the functional relevance of diastereoisomeric hapten formation. PMID:21680886

The expanding universe of neurotrophic factors: therapeutic potential in aging and age-associated disorders.

PubMed

Lanni, C; Stanga, S; Racchi, M; Govoni, S

2010-01-01

Multiple molecular, cellular, structural and functional changes occur in the brain during aging. Neural cells may respond to these changes adaptively by employing multiple mechanisms in order to maintain the integrity of nerve cell circuits and to facilitate responses to environmental demands. Otherwise, they may succumb to neurodegenerative cascades that result in disorders such as Alzheimer's and Parkinson's diseases. An important role in this balancement is played by neurotrophic factors, which are central to many aspects of nervous system function since they regulate the development, maintenance and survival of neurons and neuron-supporting cells such as glia and oligodendrocytes. A vast amount of evidence indicates that alterations in levels of neurotrophic factors or their receptors can lead to neuronal death and contribute to aging as well as to the pathogenesis of diseases of abnormal trophic support (such as neurodegenerative diseases and depression) and diseases of abnormal excitability (such as epilepsy and central pain sensitization). Cellular and molecular mechanisms by which neurotrophic factors may influence cell survival and excitability are also critically examined to provide novel concepts and targets for the treatment of physiological changes bearing detrimental functional alterations and of different diseases affecting the central nervous system during aging.

Radiogenomics: a systems biology approach to understanding genetic risk factors for radiotherapy toxicity ?

PubMed Central

Herskind, Carsten; Talbot, Christopher J.; Kerns, Sarah L.; Veldwijk, Marlon R.; Rosenstein, Barry S.; West, Catharine M. L.

2016-01-01

Adverse reactions in normal tissue after radiotherapy (RT) limit the dose that can be given to tumour cells. Since 80% of individual variation in clinical response is estimated to be caused by patient-related factors, identifying these factors might allow prediction of patients with increased risk of developing severe reactions. While inactivation of cell renewal is considered a major cause of toxicity in early-reacting normal tissues, complex interactions involving multiple cell types, cytokines, and hypoxia seem important for late reactions. Here, we review ‘omics’ approaches such as screening of genetic polymorphisms or gene expression analysis, and assess the potential of epigenetic factors, posttranslational modification, signal transduction, and metabolism. Furthermore, functional assays have suggested possible associations with clinical risk of adverse reaction. Pathway analysis incorporating different ‘omics’ approaches may be more efficient in identifying critical pathways than pathway analysis based on single ‘omics’ data sets. Integrating these pathways with functional assays may be powerful in identifying multiple subgroups of RT patients characterized by different mechanisms. Thus ‘omics’ and functional approaches may synergize if they are integrated into radiogenomics ‘systems biology’ to facilitate the goal of individualised radiotherapy. PMID:26944314

AIM: a comprehensive Arabidopsis interactome module database and related interologs in plants.

PubMed

Wang, Yi; Thilmony, Roger; Zhao, Yunjun; Chen, Guoping; Gu, Yong Q

2014-01-01

Systems biology analysis of protein modules is important for understanding the functional relationships between proteins in the interactome. Here, we present a comprehensive database named AIM for Arabidopsis (Arabidopsis thaliana) interactome modules. The database contains almost 250,000 modules that were generated using multiple analysis methods and integration of microarray expression data. All the modules in AIM are well annotated using multiple gene function knowledge databases. AIM provides a user-friendly interface for different types of searches and offers a powerful graphical viewer for displaying module networks linked to the enrichment annotation terms. Both interactive Venn diagram and power graph viewer are integrated into the database for easy comparison of modules. In addition, predicted interologs from other plant species (homologous proteins from different species that share a conserved interaction module) are available for each Arabidopsis module. AIM is a powerful systems biology platform for obtaining valuable insights into the function of proteins in Arabidopsis and other plants using the modules of the Arabidopsis interactome. Database URL:http://probes.pw.usda.gov/AIM Published by Oxford University Press 2014. This work is written by US Government employees and is in the public domain in the US.

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models

ERIC Educational Resources Information Center

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

A new approach of watermarking technique by means multichannel wavelet functions

NASA Astrophysics Data System (ADS)

Agreste, Santa; Puccio, Luigia

2012-12-01

The digital piracy involving images, music, movies, books, and so on, is a legal problem that has not found a solution. Therefore it becomes crucial to create and to develop methods and numerical algorithms in order to solve the copyright problems. In this paper we focus the attention on a new approach of watermarking technique applied to digital color images. Our aim is to describe the realized watermarking algorithm based on multichannel wavelet functions with multiplicity r = 3, called MCWM 1.0. We report a large experimentation and some important numerical results in order to show the robustness of the proposed algorithm to geometrical attacks.

Unraveling secrets of telomeres: one molecule at a time

PubMed Central

Lin, Jiangguo; Kaur, Parminder; Countryman, Preston; Opresko, Patricia L.; Wang, Hong

2016-01-01

Telomeres play important roles in maintaining the stability of linear chromosomes. Telomere maintenance involves dynamic actions of multiple proteins interacting with long repetitive sequences and complex dynamic DNA structures, such as G-quadruplexes, T-loops and t-circles. Given the heterogeneity and complexity of telomeres, single-molecule approaches are essential to fully understand the structure-function relationships that govern telomere maintenance. In this review, we present a brief overview of the principles of single-molecule imaging and manipulation techniques. We then highlight results obtained from applying these single-molecule techniques for studying structure, dynamics and functions of G-quadruplexes, telomerase, and shelterin proteins. PMID:24569170

Exercise Benefits Coronary Heart Disease.

PubMed

Wang, Lei; Ai, Dongmei; Zhang, Ning

2017-01-01

Coronary heart disease (CHD) is a group of diseases that include: no symptoms, angina, myocardial infarction, ischemia cardiomyopathy and sudden cardiac death. And it results from multiple risks factors consisting of invariable factors (e.g. age, gender, etc.) and variable factors (e.g. dyslipidemia, hypertension, diabetes, smoking, etc.). Meanwhile, CHD could cause impact not only localized in the heart, but also on pulmonary function, whole-body skeletal muscle function, activity ability, psychological status, etc. Nowadays, CHD has been the leading cause of death in the world. However, many clinical researches showed that exercise training plays an important role in cardiac rehabilitation and can bring a lot of benefits for CHD patients.

Neurocognitive and Family Functioning and Quality of Life Among Young Adult Survivors of Childhood Brain Tumors

PubMed Central

Hocking, Matthew C.; Hobbie, Wendy L.; Deatrick, Janet A.; Lucas, Matthew S.; Szabo, Margo M.; Volpe, Ellen M.; Barakat, Lamia P.

2012-01-01

Many childhood brain tumor survivors experience significant neurocognitive late effects across multiple domains that negatively affect quality of life. A theoretical model of survivorship suggests that family functioning and survivor neurocognitive functioning interact to affect survivor and family outcomes. This paper reviews the types of neurocognitive late effects experienced by survivors of pediatric brain tumors. Quantitative and qualitative data from three case reports of young adult survivors and their mothers are analyzed according to the theoretical model and presented in this paper to illustrate the importance of key factors presented in the model. The influence of age at brain tumor diagnosis, family functioning, and family adaptation to illness on survivor quality of life and family outcomes are highlighted. Future directions for research and clinical care for this vulnerable group of survivors are discussed. PMID:21722062

ASSESSMENT OF UPPER EXTREMITY IMPAIRMENT, FUNCTION, AND ACTIVITY FOLLOWING STROKE: FOUNDATIONS FOR CLINICAL DECISION MAKING

PubMed Central

Lang, Catherine E.; Bland, Marghuretta D.; Bailey, Ryan R.; Schaefer, Sydney Y.; Birkenmeier, Rebecca L.

2012-01-01

The purpose of this review is to provide a comprehensive approach for assessing the upper extremity (UE) after stroke. First, common upper extremity impairments and how to assess them are briefly discussed. While multiple UE impairments are typically present after stroke, the severity of one impairment, paresis, is the primary determinant of UE functional loss. Second, UE function is operationally defined and a number of clinical measures are discussed. It is important to consider how impairment and loss of function affect UE activity outside of the clinical environment. Thus, this review also identifies accelerometry as an objective method for assessing UE activity in daily life. Finally, the role that each of these levels of assessment should play in clinical decision making is discussed in order to optimize the provision of stroke rehabilitation services. PMID:22975740

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial

PubMed Central

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-01-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists. PMID:27134355

Improvements in cognition, quality of life, and physical performance with clinical Pilates in multiple sclerosis: a randomized controlled trial.

PubMed

Küçük, Fadime; Kara, Bilge; Poyraz, Esra Çoşkuner; İdiman, Egemen

2016-03-01

[Purpose] The aim of this study was to determine the effects of clinical Pilates in multiple sclerosis patients. [Subjects and Methods] Twenty multiple sclerosis patients were enrolled in this study. The participants were divided into two groups as the clinical Pilates and control groups. Cognition (Multiple Sclerosis Functional Composite), balance (Berg Balance Scale), physical performance (timed performance tests, Timed up and go test), tiredness (Modified Fatigue Impact scale), depression (Beck Depression Inventory), and quality of life (Multiple Sclerosis International Quality of Life Questionnaire) were measured before and after treatment in all participants. [Results] There were statistically significant differences in balance, timed performance, tiredness and Multiple Sclerosis Functional Composite tests between before and after treatment in the clinical Pilates group. We also found significant differences in timed performance tests, the Timed up and go test and the Multiple Sclerosis Functional Composite between before and after treatment in the control group. According to the difference analyses, there were significant differences in Multiple Sclerosis Functional Composite and Multiple Sclerosis International Quality of Life Questionnaire scores between the two groups in favor of the clinical Pilates group. There were statistically significant clinical differences in favor of the clinical Pilates group in comparison of measurements between the groups. Clinical Pilates improved cognitive functions and quality of life compared with traditional exercise. [Conclusion] In Multiple Sclerosis treatment, clinical Pilates should be used as a holistic approach by physical therapists.

Ketoacylsynthase Domains of a Polyunsaturated Fatty Acid Synthase in Thraustochytrium sp. Strain ATCC 26185 Can Effectively Function as Stand-Alone Enzymes in Escherichia coli.

PubMed

Xie, Xi; Meesapyodsuk, Dauenpen; Qiu, Xiao

2017-05-01

Thraustochytrium sp. strain ATCC 26185 accumulates a high level of docosahexaenoic acid (DHA), a nutritionally important ω-3 very-long-chain polyunsaturated fatty acid (VLCPUFA) synthesized primarily by polyunsaturated fatty acid (PUFA) synthase, a type I polyketide synthase-like megaenzyme. The PUFA synthase in this species comprises three large subunits, each with multiple catalytic domains. It was hypothesized that among these domains, ketoacylsynthase (KS) domains might be critical for catalyzing the condensation of specific unsaturated acyl-acyl carrier proteins (ACPs) with malonyl-ACP, thereby retaining double bonds in an extended acyl chain. To investigate the functions of these putative KS domains, two segment sequences from subunit A (KS-A) and subunit B (KS-B) of the PUFA synthase were dissected and then expressed as stand-alone enzymes in Escherichia coli The results showed that both KS-A and KS-B domains could complement the defective phenotypes of both E. coli fabB and fabF mutants. Overexpression of these domains in wild-type E. coli led to increases in total fatty acid production. KS-B produced a higher ratio of unsaturated fatty acids (UFAs) to saturated fatty acids (SFAs), while KS-A could improve the overall production of fatty acids more effectively, particularly for the production of SFAs, implying that KS-A is more comparable to FabF, while KS-B is more similar to FabB in catalytic functions. Successful complementation and functional expression of the embedded KS domains in E. coli are the first step forward in studying the molecular mechanism of the PUFA synthase for the biosynthesis of VLCPUFAs in Thraustochytrium IMPORTANCE Very-long-chain polyunsaturated fatty acids (VLCPUFAs) are important for human health. They can be biosynthesized in either an aerobic pathway or an anaerobic pathway in nature. However, abundant VLCPUFAs in marine microorganisms are primarily synthesized by polyunsaturated fatty acid (PUFA) synthase, a megaenzyme with multiple subunits, each with multiple catalytic domains. Furthermore, the fundamental mechanism for this enzyme to synthesize these fatty acids still remains unknown. This report started with dissecting the embedded KS domains of the PUFA synthase from marine protist Thraustochytrium sp. strain ATCC 26185 and then expressing them in wild-type E. coli and mutants defective in condensation of acyl-ACP with malonyl-ACP. Successful complementation of the mutants and improved fatty acid production in the overexpression experiments indicate that these KS domains can effectively function as stand-alone enzymes in E. coli This result has paved the way for further studying of molecular mechanisms of the PUFA synthase for the biosynthesis of VLCPUFAs. Copyright © 2017 American Society for Microbiology.

Ketoacylsynthase Domains of a Polyunsaturated Fatty Acid Synthase in Thraustochytrium sp. Strain ATCC 26185 Can Effectively Function as Stand-Alone Enzymes in Escherichia coli

PubMed Central

Xie, Xi; Meesapyodsuk, Dauenpen

2017-01-01

ABSTRACT Thraustochytrium sp. strain ATCC 26185 accumulates a high level of docosahexaenoic acid (DHA), a nutritionally important ω-3 very-long-chain polyunsaturated fatty acid (VLCPUFA) synthesized primarily by polyunsaturated fatty acid (PUFA) synthase, a type I polyketide synthase-like megaenzyme. The PUFA synthase in this species comprises three large subunits, each with multiple catalytic domains. It was hypothesized that among these domains, ketoacylsynthase (KS) domains might be critical for catalyzing the condensation of specific unsaturated acyl-acyl carrier proteins (ACPs) with malonyl-ACP, thereby retaining double bonds in an extended acyl chain. To investigate the functions of these putative KS domains, two segment sequences from subunit A (KS-A) and subunit B (KS-B) of the PUFA synthase were dissected and then expressed as stand-alone enzymes in Escherichia coli. The results showed that both KS-A and KS-B domains could complement the defective phenotypes of both E. coli fabB and fabF mutants. Overexpression of these domains in wild-type E. coli led to increases in total fatty acid production. KS-B produced a higher ratio of unsaturated fatty acids (UFAs) to saturated fatty acids (SFAs), while KS-A could improve the overall production of fatty acids more effectively, particularly for the production of SFAs, implying that KS-A is more comparable to FabF, while KS-B is more similar to FabB in catalytic functions. Successful complementation and functional expression of the embedded KS domains in E. coli are the first step forward in studying the molecular mechanism of the PUFA synthase for the biosynthesis of VLCPUFAs in Thraustochytrium. IMPORTANCE Very-long-chain polyunsaturated fatty acids (VLCPUFAs) are important for human health. They can be biosynthesized in either an aerobic pathway or an anaerobic pathway in nature. However, abundant VLCPUFAs in marine microorganisms are primarily synthesized by polyunsaturated fatty acid (PUFA) synthase, a megaenzyme with multiple subunits, each with multiple catalytic domains. Furthermore, the fundamental mechanism for this enzyme to synthesize these fatty acids still remains unknown. This report started with dissecting the embedded KS domains of the PUFA synthase from marine protist Thraustochytrium sp. strain ATCC 26185 and then expressing them in wild-type E. coli and mutants defective in condensation of acyl-ACP with malonyl-ACP. Successful complementation of the mutants and improved fatty acid production in the overexpression experiments indicate that these KS domains can effectively function as stand-alone enzymes in E. coli. This result has paved the way for further studying of molecular mechanisms of the PUFA synthase for the biosynthesis of VLCPUFAs. PMID:28213537

The relationship between spatial configuration and functional connectivity of brain regions.

PubMed

Bijsterbosch, Janine Diane; Woolrich, Mark W; Glasser, Matthew F; Robinson, Emma C; Beckmann, Christian F; Van Essen, David C; Harrison, Samuel J; Smith, Stephen M

2018-02-16

Brain connectivity is often considered in terms of the communication between functionally distinct brain regions. Many studies have investigated the extent to which patterns of coupling strength between multiple neural populations relates to behaviour. For example, studies have used 'functional connectivity fingerprints' to characterise individuals' brain activity. Here, we investigate the extent to which the exact spatial arrangement of cortical regions interacts with measures of brain connectivity. We find that the shape and exact location of brain regions interact strongly with the modelling of brain connectivity, and present evidence that the spatial arrangement of functional regions is strongly predictive of non-imaging measures of behaviour and lifestyle. We believe that, in many cases, cross-subject variations in the spatial configuration of functional brain regions are being interpreted as changes in functional connectivity. Therefore, a better understanding of these effects is important when interpreting the relationship between functional imaging data and cognitive traits. © 2018, Bijsterbosch et al.

A non-linear regression analysis program for describing electrophysiological data with multiple functions using Microsoft Excel.

PubMed

Brown, Angus M

2006-04-01

The objective of this present study was to demonstrate a method for fitting complex electrophysiological data with multiple functions using the SOLVER add-in of the ubiquitous spreadsheet Microsoft Excel. SOLVER minimizes the difference between the sum of the squares of the data to be fit and the function(s) describing the data using an iterative generalized reduced gradient method. While it is a straightforward procedure to fit data with linear functions, and we have previously demonstrated a method of non-linear regression analysis of experimental data based upon a single function, it is more complex to fit data with multiple functions, usually requiring specialized expensive computer software. In this paper we describe an easily understood program for fitting experimentally acquired data, in this case the stimulus-evoked compound action potential from the mouse optic nerve, with multiple Gaussian functions. The program is flexible and can be applied to describe data with a wide variety of user-input functions.

Adaptation of the Electra Radio to Support Multiple Receive Channels

NASA Technical Reports Server (NTRS)

Satorius, Edgar H.; Shah, Biren N.; Bruvold, Kristoffer N.; Bell, David J.

2011-01-01

Proposed future Mars missions plan communication between multiple assets (rovers). This paper presents the results of a study carried out to assess the potential adaptation of the Electra radio to a multi-channel transceiver. The basic concept is a Frequency Division multiplexing (FDM) communications scheme wherein different receiver architectures are examined. Options considered include: (1) multiple IF slices, A/D and FPGAs each programmed with an Electra baseband modem; (2) common IF but multiple A/Ds and FPGAs and (3) common IF, single A/D and single or multiple FPGAs programmed to accommodate the FDM signals. These options represent the usual tradeoff between analog and digital complexity. Given the space application, a common IF is preferable; however, multiple users present dynamic range challenges (e.g., near-far constraints) that would favor multiple IF slices (Option 1). Vice versa, with a common IF and multiple A/Ds (Option 2), individual AGC control of the A/Ds would be an important consideration. Option 3 would require a common AGC control strategy and would entail multiple digital down conversion paths within the FPGA. In this paper, both FDM parameters as well as the different Electra design options will be examined. In particular, signal channel spacing as a function of user data rates and transmit powers will be evaluated. In addition, tradeoffs between the different Electra design options will be presented with the ultimate goal of defining an augmented Electra radio architecture for potential future missions.

Having a Lot of a Good Thing: Multiple Important Group Memberships as a Source of Self-Esteem

PubMed Central

Jetten, Jolanda; Branscombe, Nyla R.; Haslam, S. Alexander; Haslam, Catherine; Cruwys, Tegan; Jones, Janelle M.; Cui, Lijuan; Dingle, Genevieve; Liu, James; Murphy, Sean; Thai, Anh; Walter, Zoe; Zhang, Airong

2015-01-01

Membership in important social groups can promote a positive identity. We propose and test an identity resource model in which personal self-esteem is boosted by membership in additional important social groups. Belonging to multiple important group memberships predicts personal self-esteem in children (Study 1a), older adults (Study 1b), and former residents of a homeless shelter (Study 1c). Study 2 shows that the effects of multiple important group memberships on personal self-esteem are not reducible to number of interpersonal ties. Studies 3a and 3b provide longitudinal evidence that multiple important group memberships predict personal self-esteem over time. Studies 4 and 5 show that collective self-esteem mediates this effect, suggesting that membership in multiple important groups boosts personal self-esteem because people take pride in, and derive meaning from, important group memberships. Discussion focuses on when and why important group memberships act as a social resource that fuels personal self-esteem. PMID:26017554

The importance of the function of exercise in the relationship between obligatory exercise and eating and body image concerns.

PubMed

De Young, Kyle P; Anderson, Drew A

2010-01-01

This study tested whether exercising in response to negative affect moderates the association between obligatory exercise and eating and body image psychopathology. Participants (n=226) completed the Eating Disorders Examination-Questionnaire (EDE-Q), Obligatory Exercise Questionnaire (OEQ), and a question assessing whether they ever exercise in response to negative affect. In total, 132 (58.4%) participants endorsed exercising in response to negative affect. Multiple regression analyses revealed significant main effects of negative affect motivated exercise, OEQ total scores, and gender on all four EDE-Q subscales and significant interactions of negative affect motivated exercise and OEQ scores on the Eating Concern, Shape Concern, and Weight Concern scales but not the Restraint scale of the EDE-Q. Obligatory exercisers may not demonstrate elevated eating and body image concerns in the absence of negative affect motivated exercise, providing further support of the importance of the function of exercise.

An epigenetic view of developmental diseases: new targets, new therapies.

PubMed

Xie, Pei; Zang, Li-Qun; Li, Xue-Kun; Shu, Qiang

2016-08-01

Function of epigenetic modifications is one of the most competitive fields in life science. Over the past several decades, it has been revealed that epigenetic modifications play essential roles in development and diseases including developmental diseases. In the present review, we summarize the recent progress about the function of epigenetic regulation, especially DNA and RNA modifications in developmental diseases. Original research articles and literature reviews published in PubMed-indexed journals. DNA modifications including methylation and demethylation can regulate gene expression, and are involved in development and multiple diseases including Rett syndrome, Autism spectrum disorders, congenital heart disease and cancer, etc. RNA methylation and demethylation play important roles in RNA processing, reprogramming, circadian, and neuronal activity, and then modulate development. DNA and RNA modifications play important roles in development and diseases through regulating gene expression. Epigenetic components could serve as novel targets for the treatment of developmental diseases.

Using Knowledge of Chemical and Structural Defenses of Seaweeds to Develop a Standardized Measure of Herbivory in Tropical and Subtropical Habitats

NASA Astrophysics Data System (ADS)

Paul, V. J.

2016-02-01

Herbivory is an important process determining the structure and function of marine ecosystems, and this is especially true on coral reefs and in associated tropical and subtropical habitats where grazing by fishes can be intense. As reef degradation is occurring on a global scale, and overfishing can contribute to this problem, rates of herbivory can be an important indicator of reef function and resilience. Our goal was to develop a standardized herbivory assay that can be deployed globally to measure the impact of herbivorous fishes across multiple habitat types. Many tropical and subtropical seaweeds contain chemical and structural defenses that can protect them from herbivores, and this information was key to selecting a range of marine plants that are differentially palatable to herbivorous fishes for these assays. We present method development and experimental results from extensive deployment of these herbivory assays at Carrie Bow Cay, Belize.

Multiple paternity and sporophytic inbreeding depression in a dioicous moss species.

PubMed

Szövényi, P; Ricca, M; Shaw, A J

2009-11-01

Multiple paternity (polyandry) frequently occurs in flowering plants and animals and is assumed to have an important function in the evolution of reproductive traits. Polyandry in bryophytes may occur among multiple sporophytes of a female gametophyte; however, its occurrence and extent is unknown. In this study we investigate the occurrence and extent of multiple paternity, spatial genetic structure, and sporophytic inbreeding depression in natural populations of a dioicous bryophyte species, Sphagnum lescurii, using microsatellite markers. Multiple paternity is prevalent among sporophytes of a female gametophyte and male genotypes exhibit significant skew in paternity. Despite significant spatial genetic structure in the population, suggesting frequent inbreeding, the number of inbred and outbred sporophytes was balanced, resulting in an average fixation coefficient and population level selfing rate of zero. In line with the prediction of sporophytic inbreeding depression sporophyte size was significantly correlated with the level of heterozygosity. Furthermore, female gametophytes preferentially supported sporophytes with higher heterozygosity. These results indicate that polyandry provides the opportunity for postfertilization selection in bryophytes having short fertilization distances and spatially structured populations facilitating inbreeding. Preferential maternal support of the more heterozygous sporophytes suggests active inbreeding avoidance that may have significant implications for mating system evolution in bryophytes.

[Incomplete Carney's Triad and arterial hypertension in a young woman].

PubMed

Allievi, Alberto; Araya, Valentina; Calvar, Cecilia; Cimino, Conrado; Delle Piane, Hugo; Diaz, Gabriela; Gianni, Marta; Prudkin, Ludmila

2006-01-01

The case of young woman with arterial hypertension diagnosed two years before, is here presented; she had a ferropenic anemia caused by digestive loss of blood. Multiple gastric tumors and pararenal non functioning paraganglioma were found. No chondromas were detected. An incomplete Carney's Triad was diagnosed. We remark that multiple gastric tumors in a young adult suggest the possibility of gastrointestinal stromal tumors (GIST) Endoscopic biopsy frequently is not effective because these tumors are deep placed in the muscular gastric layers. The importance of specific techniques for a positive diagnosis are emphasized. Continuous follow up is needed because these tumors have uncertain prognosis. Lung chondromas may appear years later after the GIST was removed and might be confused with GIST metastases.

Prolonged delirium misdiagnosed as a mood disorder.

PubMed

Cao, Fei; Salem, Haitham; Nagpal, Caesa; Teixeira, Antonio L

2017-01-01

Delirium can be conceptualized as an acute decline in cognitive function that typically lasts from hours to a few days. Prolonged delirium can also affect patients with multiple predisposing and/or precipitating factors. In clinical practice, prolonged delirium is often unrecognized, and can be misdiagnosed as other psychiatric disorders. We describe a case of a 59-year-old male presenting with behavioral and cognitive symptoms that was first misdiagnosed as a mood disorder in a general hospital setting. After prolonged delirium due to multiple factors was confirmed, the patient was treated accordingly with symptomatic management. He evolved with progressive improvement of his clinical status. Early diagnosis and management of prolonged delirium are important to improve patient prognosis and avoid iatrogenic measures.

Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) for Conformational Space Search of Peptide and Miniprotein

PubMed Central

Hao, Ge-Fei; Xu, Wei-Fang; Yang, Sheng-Gang; Yang, Guang-Fu

2015-01-01

Protein and peptide structure predictions are of paramount importance for understanding their functions, as well as the interactions with other molecules. However, the use of molecular simulation techniques to directly predict the peptide structure from the primary amino acid sequence is always hindered by the rough topology of the conformational space and the limited simulation time scale. We developed here a new strategy, named Multiple Simulated Annealing-Molecular Dynamics (MSA-MD) to identify the native states of a peptide and miniprotein. A cluster of near native structures could be obtained by using the MSA-MD method, which turned out to be significantly more efficient in reaching the native structure compared to continuous MD and conventional SA-MD simulation. PMID:26492886

Integrating the ICF with positive psychology: Factors predicting role participation for mothers with multiple sclerosis.

PubMed

Farber, Ruth S; Kern, Margaret L; Brusilovsky, Eugene

2015-05-01

Being a mother has become a realizable life role for women with disabilities and chronic illnesses, including multiple sclerosis (MS). Identifying psychosocial factors that facilitate participation in important life roles-including motherhood-is essential to help women have fuller lives despite the challenge of their illness. By integrating the International Classification of Functioning, Disability, and Health (ICF) and a positive psychology perspective, this study examined how environmental social factors and positive personal factors contribute to daily role participation and satisfaction with parental participation. One hundred and 11 community-dwelling mothers with MS completed Ryff's Psychological Well-Being Scales, the Medical Outcome Study Social Support Survey, the Short Form-36, and the Parental Participation Scale. Hierarchical regression analyses examined associations between social support and positive personal factors (environmental mastery, self-acceptance, purpose in life) with daily role participation (physical and emotional) and satisfaction with parental participation. One-way ANOVAs tested synergistic combinations of social support and positive personal factors. Social support predicted daily role participation (fewer limitations) and greater satisfaction with parental participation. Positive personal factors contributed additional unique variance. Positive personal factors and social support synergistically predicted better function and greater satisfaction than either alone. Integrating components of the ICF and positive psychology provides a useful model for understanding how mothers with MS can thrive despite challenge or impairment. Both positive personal factors and environmental social factors were important contributors to positive role functioning. Incorporating these paradigms into treatment may help mothers with MS participate more fully in meaningful life roles. (c) 2015 APA, all rights reserved).

Annual grass invasion in sagebrush-steppe: The relative importance of climate, soil properties and biotic interactions

USGS Publications Warehouse

Bansal, Sheel; Sheley, Roger L.

2016-01-01

The invasion by winter-annual grasses (AGs) such as Bromus tectorum into sagebrush steppe throughout the western USA is a classic example of a biological invasion with multiple, interacting climate, soil and biotic factors driving the invasion, although few studies have examined all components together. Across a 6000-km2 area of the northern Great Basin, we conducted a field assessment of 100 climate, soil, and biotic (functional group abundances, diversity) factors at each of 90 sites that spanned an invasion gradient ranging from 0 to 100 % AG cover. We first determined which biotic and abiotic factors had the strongest correlative relationships with AGs and each resident functional group. We then used regression and structural equation modeling to explore how multiple ecological factors interact to influence AG abundance. Among biotic interactions, we observed negative relationships between AGs and biodiversity, perennial grass cover, resident species richness, biological soil crust cover and shrub density, whereas perennial and annual forb cover, tree cover and soil microbial biomass had no direct linkage to AG. Among abiotic factors, AG cover was strongly related to climate (increasing cover with increasing temperature and aridity), but had weak relationships with soil factors. Our structural equation model showed negative effects of perennial grasses and biodiversity on AG cover while integrating the negative effects of warmer climate and positive influence of belowground processes on resident functional groups. Our findings illustrate the relative importance of biotic interactions and climate on invasive abundance, while soil properties appear to have stronger relationships with resident biota than with invasives.

GenPlay Multi-Genome, a tool to compare and analyze multiple human genomes in a graphical interface.

PubMed

Lajugie, Julien; Fourel, Nicolas; Bouhassira, Eric E

2015-01-01

Parallel visualization of multiple individual human genomes is a complex endeavor that is rapidly gaining importance with the increasing number of personal, phased and cancer genomes that are being generated. It requires the display of variants such as SNPs, indels and structural variants that are unique to specific genomes and the introduction of multiple overlapping gaps in the reference sequence. Here, we describe GenPlay Multi-Genome, an application specifically written to visualize and analyze multiple human genomes in parallel. GenPlay Multi-Genome is ideally suited for the comparison of allele-specific expression and functional genomic data obtained from multiple phased genomes in a graphical interface with access to multiple-track operation. It also allows the analysis of data that have been aligned to custom genomes rather than to a standard reference and can be used as a variant calling format file browser and as a tool to compare different genome assembly, such as hg19 and hg38. GenPlay is available under the GNU public license (GPL-3) from http://genplay.einstein.yu.edu. The source code is available at https://github.com/JulienLajugie/GenPlay. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Plant structure predicts leaf litter capture in the tropical montane bromeliad Tillandsia turneri.

PubMed

Ospina-Bautista, F; Estévez Varón, J V

2016-05-03

Leaves intercepted by bromeliads become an important energy and matter resource for invertebrate communities, bacteria, fungi, and the plant itself. The relationship between bromeliad structure, defined as its size and complexity, and accumulated leaf litter was studied in 55 bromeliads of Tillandsia turneri through multiple regression and the Akaike information criterion. Leaf litter accumulation in bromeliads was best explained by size and complexity variables such as plant cover, sheath length, and leaf number. In conclusion, plant structure determines the amount of litter that enters bromeliads, and changes in its structure could affect important processes within ecosystem functioning or species richness.

Managing multiple image stacks from confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Zerbe, Joerg; Goetze, Christian H.; Zuschratter, Werner

1999-05-01

A major goal in neuroanatomy is to obtain precise information about the functional organization of neuronal assemblies and their interconnections. Therefore, the analysis of histological sections frequently requires high resolution images in combination with an overview about the structure. To overcome this conflict we have previously introduced a software for the automatic acquisition of multiple image stacks (3D-MISA) in confocal laser scanning microscopy. Here, we describe a Windows NT based software for fast and easy navigation through the multiple images stacks (MIS-browser), the visualization of individual channels and layers and the selection of user defined subregions. In addition, the MIS browser provides useful tools for the visualization and evaluation of the datavolume, as for instance brightness and contrast corrections of individual layers and channels. Moreover, it includes a maximum intensity projection, panning and zoom in/out functions within selected channels or focal planes (x/y) and tracking along the z-axis. The import module accepts any tiff-format and reconstructs the original image arrangement after the user has defined the sequence of images in x/y and z and the number of channels. The implemented export module allows storage of user defined subregions (new single image stacks) for further 3D-reconstruction and evaluation.

An effective and robust method for tracking multiple fish in video image based on fish head detection.

PubMed

Qian, Zhi-Ming; Wang, Shuo Hong; Cheng, Xi En; Chen, Yan Qiu

2016-06-23

Fish tracking is an important step for video based analysis of fish behavior. Due to severe body deformation and mutual occlusion of multiple swimming fish, accurate and robust fish tracking from video image sequence is a highly challenging problem. The current tracking methods based on motion information are not accurate and robust enough to track the waving body and handle occlusion. In order to better overcome these problems, we propose a multiple fish tracking method based on fish head detection. The shape and gray scale characteristics of the fish image are employed to locate the fish head position. For each detected fish head, we utilize the gray distribution of the head region to estimate the fish head direction. Both the position and direction information from fish detection are then combined to build a cost function of fish swimming. Based on the cost function, global optimization method can be applied to associate the target between consecutive frames. Results show that our method can accurately detect the position and direction information of fish head, and has a good tracking performance for dozens of fish. The proposed method can successfully obtain the motion trajectories for dozens of fish so as to provide more precise data to accommodate systematic analysis of fish behavior.

Toward a Dynamically Reconfigurable Computing and Communication System for Small Spacecraft

NASA Technical Reports Server (NTRS)

Kifle, Muli; Andro, Monty; Tran, Quang K.; Fujikawa, Gene; Chu, Pong P.

2003-01-01

Future science missions will require the use of multiple spacecraft with multiple sensor nodes autonomously responding and adapting to a dynamically changing space environment. The acquisition of random scientific events will require rapidly changing network topologies, distributed processing power, and a dynamic resource management strategy. Optimum utilization and configuration of spacecraft communications and navigation resources will be critical in meeting the demand of these stringent mission requirements. There are two important trends to follow with respect to NASA's (National Aeronautics and Space Administration) future scientific missions: the use of multiple satellite systems and the development of an integrated space communications network. Reconfigurable computing and communication systems may enable versatile adaptation of a spacecraft system's resources by dynamic allocation of the processor hardware to perform new operations or to maintain functionality due to malfunctions or hardware faults. Advancements in FPGA (Field Programmable Gate Array) technology make it possible to incorporate major communication and network functionalities in FPGA chips and provide the basis for a dynamically reconfigurable communication system. Advantages of higher computation speeds and accuracy are envisioned with tremendous hardware flexibility to ensure maximum survivability of future science mission spacecraft. This paper discusses the requirements, enabling technologies, and challenges associated with dynamically reconfigurable space communications systems.

Protein Structure Classification and Loop Modeling Using Multiple Ramachandran Distributions.

PubMed

Najibi, Seyed Morteza; Maadooliat, Mehdi; Zhou, Lan; Huang, Jianhua Z; Gao, Xin

2017-01-01

Recently, the study of protein structures using angular representations has attracted much attention among structural biologists. The main challenge is how to efficiently model the continuous conformational space of the protein structures based on the differences and similarities between different Ramachandran plots. Despite the presence of statistical methods for modeling angular data of proteins, there is still a substantial need for more sophisticated and faster statistical tools to model the large-scale circular datasets. To address this need, we have developed a nonparametric method for collective estimation of multiple bivariate density functions for a collection of populations of protein backbone angles. The proposed method takes into account the circular nature of the angular data using trigonometric spline which is more efficient compared to existing methods. This collective density estimation approach is widely applicable when there is a need to estimate multiple density functions from different populations with common features. Moreover, the coefficients of adaptive basis expansion for the fitted densities provide a low-dimensional representation that is useful for visualization, clustering, and classification of the densities. The proposed method provides a novel and unique perspective to two important and challenging problems in protein structure research: structure-based protein classification and angular-sampling-based protein loop structure prediction.

Conditional Spectral Analysis of Replicated Multiple Time Series with Application to Nocturnal Physiology.

PubMed

Krafty, Robert T; Rosen, Ori; Stoffer, David S; Buysse, Daniel J; Hall, Martica H

2017-01-01

This article considers the problem of analyzing associations between power spectra of multiple time series and cross-sectional outcomes when data are observed from multiple subjects. The motivating application comes from sleep medicine, where researchers are able to non-invasively record physiological time series signals during sleep. The frequency patterns of these signals, which can be quantified through the power spectrum, contain interpretable information about biological processes. An important problem in sleep research is drawing connections between power spectra of time series signals and clinical characteristics; these connections are key to understanding biological pathways through which sleep affects, and can be treated to improve, health. Such analyses are challenging as they must overcome the complicated structure of a power spectrum from multiple time series as a complex positive-definite matrix-valued function. This article proposes a new approach to such analyses based on a tensor-product spline model of Cholesky components of outcome-dependent power spectra. The approach exibly models power spectra as nonparametric functions of frequency and outcome while preserving geometric constraints. Formulated in a fully Bayesian framework, a Whittle likelihood based Markov chain Monte Carlo (MCMC) algorithm is developed for automated model fitting and for conducting inference on associations between outcomes and spectral measures. The method is used to analyze data from a study of sleep in older adults and uncovers new insights into how stress and arousal are connected to the amount of time one spends in bed.

Factors Influencing Amount of Weekly Exercise Time in Colorectal Cancer Survivors.

PubMed

Chou, Yun-Jen; Lai, Yeur-Hur; Lin, Been-Ren; Liang, Jin-Tung; Shun, Shiow-Ching

Performing regular exercise of at least 150 minutes weekly has benefits for colorectal cancer survivors. However, barriers inhibit these survivors from performing regular exercise. The aim of this study was to explore exercise behaviors and significant factors influencing weekly exercise time of more than 150 minutes in colorectal cancer survivors. A cross-sectional study design was used to recruit participants in Taiwan. Guided by the ecological model of health behavior, exercise barriers were assessed including intrapersonal, interpersonal, and environment-related barriers. A multiple logistic regression was used to explore the factors associated with the amount of weekly exercise. Among 321 survivors, 57.0% of them had weekly exercise times of more than 150 minutes. The results identified multiple levels of significant factors related to weekly exercise times including intrapersonal factors (occupational status, functional status, pain, interest in exercise, and beliefs about the importance of exercise) and exercise barriers related to environmental factors (lack of time and bad weather). No interpersonal factors were found to be significant. Colorectal cancer survivors experienced low levels of physical and psychological distress. Multiple levels of significant factors related to exercise time including intrapersonal factors as well as exercise barriers related to environmental factors should be considered. Healthcare providers should discuss with their patients how to perform exercise programs; the discussion should address multiple levels of the ecological model such as any pain problems, functional status, employment status, and time limitations, as well as community environment.

The opercular mouth-opening mechanism of largemouth bass functions as a 3D four-bar linkage with three degrees of freedom.

PubMed

Olsen, Aaron M; Camp, Ariel L; Brainerd, Elizabeth L

2017-12-15

The planar, one degree of freedom (1-DoF) four-bar linkage is an important model for understanding the function, performance and evolution of numerous biomechanical systems. One such system is the opercular mechanism in fishes, which is thought to function like a four-bar linkage to depress the lower jaw. While anatomical and behavioral observations suggest some form of mechanical coupling, previous attempts to model the opercular mechanism as a planar four-bar have consistently produced poor model fits relative to observed kinematics. Using newly developed, open source mechanism fitting software, we fitted multiple three-dimensional (3D) four-bar models with varying DoF to in vivo kinematics in largemouth bass to test whether the opercular mechanism functions instead as a 3D four-bar with one or more DoF. We examined link position error, link rotation error and the ratio of output to input link rotation to identify a best-fit model at two different levels of variation: for each feeding strike and across all strikes from the same individual. A 3D, 3-DoF four-bar linkage was the best-fit model for the opercular mechanism, achieving link rotational errors of less than 5%. We also found that the opercular mechanism moves with multiple degrees of freedom at the level of each strike and across multiple strikes. These results suggest that active motor control may be needed to direct the force input to the mechanism by the axial muscles and achieve a particular mouth-opening trajectory. Our results also expand the versatility of four-bar models in simulating biomechanical systems and extend their utility beyond planar or single-DoF systems. © 2017. Published by The Company of Biologists Ltd.

VoxelStats: A MATLAB Package for Multi-Modal Voxel-Wise Brain Image Analysis.

PubMed

Mathotaarachchi, Sulantha; Wang, Seqian; Shin, Monica; Pascoal, Tharick A; Benedet, Andrea L; Kang, Min Su; Beaudry, Thomas; Fonov, Vladimir S; Gauthier, Serge; Labbe, Aurélie; Rosa-Neto, Pedro

2016-01-01

In healthy individuals, behavioral outcomes are highly associated with the variability on brain regional structure or neurochemical phenotypes. Similarly, in the context of neurodegenerative conditions, neuroimaging reveals that cognitive decline is linked to the magnitude of atrophy, neurochemical declines, or concentrations of abnormal protein aggregates across brain regions. However, modeling the effects of multiple regional abnormalities as determinants of cognitive decline at the voxel level remains largely unexplored by multimodal imaging research, given the high computational cost of estimating regression models for every single voxel from various imaging modalities. VoxelStats is a voxel-wise computational framework to overcome these computational limitations and to perform statistical operations on multiple scalar variables and imaging modalities at the voxel level. VoxelStats package has been developed in Matlab(®) and supports imaging formats such as Nifti-1, ANALYZE, and MINC v2. Prebuilt functions in VoxelStats enable the user to perform voxel-wise general and generalized linear models and mixed effect models with multiple volumetric covariates. Importantly, VoxelStats can recognize scalar values or image volumes as response variables and can accommodate volumetric statistical covariates as well as their interaction effects with other variables. Furthermore, this package includes built-in functionality to perform voxel-wise receiver operating characteristic analysis and paired and unpaired group contrast analysis. Validation of VoxelStats was conducted by comparing the linear regression functionality with existing toolboxes such as glim_image and RMINC. The validation results were identical to existing methods and the additional functionality was demonstrated by generating feature case assessments (t-statistics, odds ratio, and true positive rate maps). In summary, VoxelStats expands the current methods for multimodal imaging analysis by allowing the estimation of advanced regional association metrics at the voxel level.

The same pocket in menin binds both MLL and JUND but has opposite effects on transcription

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

Huang, Jing; Gurung, Buddha; Wan, Bingbing

2013-04-08

Menin is a tumour suppressor protein whose loss or inactivation causes multiple endocrine neoplasia 1 (MEN1), a hereditary autosomal dominant tumour syndrome that is characterized by tumorigenesis in multiple endocrine organs. Menin interacts with many proteins and is involved in a variety of cellular processes. Menin binds the JUN family transcription factor JUND and inhibits its transcriptional activity. Several MEN1 missense mutations disrupt the menin-JUND interaction, suggesting a correlation between the tumour-suppressor function of menin and its suppression of JUND-activated transcription. Menin also interacts with mixed lineage leukaemia protein 1 (MLL1), a histone H3 lysine 4 methyltransferase, and functions asmore » an oncogenic cofactor to upregulate gene transcription and promote MLL1-fusion-protein-induced leukaemogenesis. A recent report on the tethering of MLL1 to chromatin binding factor lens epithelium-derived growth factor (LEDGF) by menin indicates that menin is a molecular adaptor coordinating the functions of multiple proteins. Despite its importance, how menin interacts with many distinct partners and regulates their functions remains poorly understood. Here we present the crystal structures of human menin in its free form and in complexes with MLL1 or with JUND, or with an MLL1-LEDGF heterodimer. These structures show that menin contains a deep pocket that binds short peptides of MLL1 or JUND in the same manner, but that it can have opposite effects on transcription. The menin-JUND interaction blocks JUN N-terminal kinase (JNK)-mediated JUND phosphorylation and suppresses JUND-induced transcription. In contrast, menin promotes gene transcription by binding the transcription activator MLL1 through the peptide pocket while still interacting with the chromatin-anchoring protein LEDGF at a distinct surface formed by both menin and MLL1.« less

Pronounced Structural and Functional Damage in Early Adult Pediatric-Onset Multiple Sclerosis with No or Minimal Clinical Disability.

PubMed

Giorgio, Antonio; Zhang, Jian; Stromillo, Maria Laura; Rossi, Francesca; Battaglini, Marco; Nichelli, Lucia; Mortilla, Marzia; Portaccio, Emilio; Hakiki, Bahia; Amato, Maria Pia; De Stefano, Nicola

2017-01-01

Pediatric-onset multiple sclerosis (POMS) may represent a model of vulnerability to damage occurring during a period of active maturation of the human brain. Whereas adaptive mechanisms seem to take place in the POMS brain in the short-medium term, natural history studies have shown that these patients reach irreversible disability, despite slower progression, at a significantly younger age than adult-onset MS (AOMS) patients. We tested for the first time whether significant brain alterations already occurred in POMS patients in their early adulthood and with no or minimal disability ( n  = 15) in comparison with age- and disability-matched AOMS patients ( n  = 14) and to normal controls (NC, n  = 20). We used a multimodal MRI approach by modeling, using FSL, voxelwise measures of microstructural integrity of white matter tracts and gray matter volumes with those of intra- and internetwork functional connectivity (FC) (analysis of variance, p  ≤ 0.01, corrected for multiple comparisons across space). POMS patients showed, when compared with both NC and AOMS patients, altered measures of diffusion tensor imaging (reduced fractional anisotropy and/or increased diffusivities) and higher probability of lesion occurrence in a clinically eloquent region for physical disability such as the posterior corona radiata. In addition, POMS patients showed, compared with the other two groups, reduced long-range FC, assessed from resting functional MRI, between default mode network and secondary visual network, whose interaction subserves important cognitive functions such as spatial attention and visual learning. Overall, this pattern of structural damage and brain connectivity disruption in early adult POMS patients with no or minimal clinical disability might explain their unfavorable clinical outcome in the long term.

Analysis of the Yule-Nielsen effect with the multiple-path point spread function in a frequency-modulated halftone.

PubMed

Rogers, Geoffrey

2018-06-01

The Yule-Nielsen effect is an influence on halftone color caused by the diffusion of light within the paper upon which the halftone ink is printed. The diffusion can be characterized by a point spread function. In this paper, a point spread function for paper is derived using the multiple-path model of reflection. This model treats the interaction of light with turbid media as a random walk. Using the multiple-path point spread function, a general expression is derived for the average reflectance of light from a frequency-modulated halftone, in which dot size is constant and the number of dots is varied, with the arrangement of dots random. It is also shown that the line spread function derived from the multiple-path model has the form of a Lorentzian function.

Enhanced disease characterization through multi network functional normalization in fMRI.

PubMed

Çetin, Mustafa S; Khullar, Siddharth; Damaraju, Eswar; Michael, Andrew M; Baum, Stefi A; Calhoun, Vince D

2015-01-01

Conventionally, structural topology is used for spatial normalization during the pre-processing of fMRI. The co-existence of multiple intrinsic networks which can be detected in the resting brain are well-studied. Also, these networks exhibit temporal and spatial modulation during cognitive task vs. rest which shows the existence of common spatial excitation patterns between these identified networks. Previous work (Khullar et al., 2011) has shown that structural and functional data may not have direct one-to-one correspondence and functional activation patterns in a well-defined structural region can vary across subjects even for a well-defined functional task. The results of this study and the existence of the neural activity patterns in multiple networks motivates us to investigate multiple resting-state networks as a single fusion template for functional normalization for multi groups of subjects. We extend the previous approach (Khullar et al., 2011) by co-registering multi group of subjects (healthy control and schizophrenia patients) and by utilizing multiple resting-state networks (instead of just one) as a single fusion template for functional normalization. In this paper we describe the initial steps toward using multiple resting-state networks as a single fusion template for functional normalization. A simple wavelet-based image fusion approach is presented in order to evaluate the feasibility of combining multiple functional networks. Our results showed improvements in both the significance of group statistics (healthy control and schizophrenia patients) and the spatial extent of activation when a multiple resting-state network applied as a single fusion template for functional normalization after the conventional structural normalization. Also, our results provided evidence that the improvement in significance of group statistics lead to better accuracy results for classification of healthy controls and schizophrenia patients.

The function of neurocognitive networks. Comment on “Understanding brain networks and brain organization” by Pessoa

NASA Astrophysics Data System (ADS)

Bressler, Steven L.

2014-09-01

Pessoa [5] has performed a valuable service by reviewing the extant literature on brain networks and making a number of interesting proposals about their cognitive function. The term function is at the core of understanding the brain networks of cognition, or neurocognitive networks (NCNs) [1]. The great Russian neuropsychologist, Luria [4], defined brain function as the common task executed by a distributed brain network of complex dynamic structures united by the demands of cognition. Casting Luria in a modern light, we can say that function emerges from the interactions of brain regions in NCNs as they dynamically self-organize according to cognitive demands. Pessoa rightly details the mapping between brain function and structure, emphasizing both its pluripotency (one structure having multiple functions) and degeneracy (many structures having the same function). However, he fails to consider the potential importance of a one-to-one mapping between NCNs and function. If NCNs are uniquely composed of specific collections of brain areas, then each NCN has a unique function determined by that composition.

Escherichia coli O157:H7 Strain EDL933 Harbors Multiple Functional Prophage-Associated Genes Necessary for the Utilization of 5-N-Acetyl-9-O-Acetyl Neuraminic Acid as a Growth Substrate

PubMed Central

Saile, Nadja; Voigt, Anja; Kessler, Sarah; Stressler, Timo; Fischer, Lutz

2016-01-01

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain EDL933 harbors multiple prophage-associated open reading frames (ORFs) in its genome which are highly homologous to the chromosomal nanS gene. The latter is part of the nanCMS operon, which is present in most E. coli strains and encodes an esterase which is responsible for the monodeacetylation of 5-N-acetyl-9-O-acetyl neuraminic acid (Neu5,9Ac2). Whereas one prophage-borne ORF (z1466) has been characterized in previous studies, the functions of the other nanS-homologous ORFs are unknown. In the current study, the nanS-homologous ORFs of EDL933 were initially studied in silico. Due to their homology to the chromosomal nanS gene and their location in prophage genomes, we designated them nanS-p and numbered the different nanS-p alleles consecutively from 1 to 10. The two alleles nanS-p2 and nanS-p4 were selected for production of recombinant proteins, their enzymatic activities were investigated, and differences in their temperature optima were found. Furthermore, a function of these enzymes in substrate utilization could be demonstrated using an E. coli C600ΔnanS mutant in a growth medium with Neu5,9Ac2 as the carbon source and supplementation with the different recombinant NanS-p proteins. Moreover, generation of sequential deletions of all nanS-p alleles in strain EDL933 and subsequent growth experiments demonstrated a gene dose effect on the utilization of Neu5,9Ac2. Since Neu5,9Ac2 is an important component of human and animal gut mucus and since the nutrient availability in the large intestine is limited, we hypothesize that the presence of multiple Neu5,9Ac2 esterases provides them a nutrient supply under certain conditions in the large intestine, even if particular prophages are lost. IMPORTANCE In this study, a group of homologous prophage-borne nanS-p alleles and two of the corresponding enzymes of enterohemorrhagic E. coli (EHEC) O157:H7 strain EDL933 that may be important to provide alternative genes for substrate utilization were characterized. PMID:27474715

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

PubMed Central

Gesbert, Gael; Ramond, Elodie; Tros, Fabiola; Dairou, Julien; Frapy, Eric; Barel, Monique

2014-01-01

Intracellular bacterial pathogens have adapted their metabolism to optimally utilize the nutrients available in infected host cells. We recently reported the identification of an asparagine transporter required specifically for cytosolic multiplication of Francisella. In the present work, we characterized a new member of the major super family (MSF) of transporters, involved in isoleucine uptake. We show that this transporter (here designated IleP) plays a critical role in intracellular metabolic adaptation of Francisella. Inactivation of IleP severely impaired intracellular F. tularensis subsp. novicida multiplication in all cell types tested and reduced bacterial virulence in the mouse model. To further establish the importance of the ileP gene in F. tularensis pathogenesis, we constructed a chromosomal deletion mutant of ileP (ΔFTL_1803) in the F. tularensis subsp. holarctica live vaccine strain (LVS). Inactivation of IleP in the F. tularensis LVS provoked comparable intracellular growth defects, confirming the critical role of this transporter in isoleucine uptake. The data presented establish, for the first time, the importance of isoleucine utilization for efficient phagosomal escape and cytosolic multiplication of Francisella and suggest that virulent F. tularensis subspecies have lost their branched-chain amino acid biosynthetic pathways and rely exclusively on dedicated uptake systems. This loss of function is likely to reflect an evolution toward a predominantly intracellular life style of the pathogen. Amino acid transporters should be thus considered major players in the adaptation of intracellular pathogens. PMID:25332124

Ecological engineering helps maximize function in algal oil production.

PubMed

Jackrel, Sara L; Narwani, Anita; Bentlage, Bastian; Levine, Robert B; Hietala, David C; Savage, Phillip E; Oakley, Todd H; Denef, Vincent J; Cardinale, Bradley J

2018-05-18

Algal biofuels have the potential to curb emissions of greenhouse gases from fossil fuels, but current growing methods fail to produce fuels that meet the multiple standards necessary for economical industrial use. For example, algae grown as monocultures for biofuel production have not simultaneously and economically achieved high yields of the high-quality, lipid-rich biomass desired for the industrial-scale production of bio-oil. Decades of study in the field of ecology have demonstrated that simultaneous increases in multiple functions, such as the quantity and quality of biomass, can occur in natural ecosystems by increasing biological diversity. Here we show that species consortia of algae can improve the production of bio-oil, which benefits from both high biomass yield and high quality of biomass rich in fatty acids. We explain the underlying causes of increased quantity and quality of algal biomass among species consortia by showing that, relative to monocultures, species consortia can differentially regulate lipid metabolism genes while growing to higher levels of biomass, in part due to greater utilization of nutrient resources. We identify multiple genes involved in lipid biosynthesis that are frequently upregulated in bicultures, and further show that these elevated levels of gene expression are highly predictive of the elevated levels in biculture relative to monoculture of multiple quality metrics of algal biomass. These results show that interactions between species can alter the expression of lipid metabolism genes, and further demonstrate that our understanding of diversity-function relationships from natural ecosystems can be harnessed to improve production of bio-oil. Importance section: Algal biofuels are one of the more promising forms of renewable energy. In our study, we investigate whether ecological interactions between species of microalgae regulate two important factors in cultivation - the biomass of the crop produced and quality of the biomass that is produced. We find that species interactions often improved production yields, especially the fatty acid content of the algal biomass, and that differentially expressed genes involved in fatty acid metabolism are predictive of improved quality metrics of bio-oil. Other studies have found that diversity often improves productivity and stability in agricultural and natural ecosystems. Our results provide further evidence that growing multi-species crops of microalgae may improve the production of high-quality biomass for bio-oil. Copyright © 2018 American Society for Microbiology.

Managing hydrological measurements for small and intermediate projects: RObsDat

NASA Astrophysics Data System (ADS)

Reusser, Dominik E.

2014-05-01

Hydrological measurements need good management for the data not to be lost. Multiple, often overlapping files from various loggers with heterogeneous formats need to be merged. Data needs to be validated and cleaned and subsequently converted to the format for the hydrological target application. Preferably, all these steps should be easily tracable. RObsDat is an R package designed to support such data management. It comes with a command line user interface to support hydrologists to enter and adjust their data in a database following the Observations Data Model (ODM) standard by QUASHI. RObsDat helps in the setup of the database within one of the free database engines MySQL, PostgreSQL or SQLite. It imports the controlled water vocabulary from the QUASHI web service and provides a smart interface between the hydrologist and the database: Already existing data entries are detected and duplicates avoided. The data import function converts different data table designes to make import simple. Cleaning and modifications of data are handled with a simple version control system. Variable and location names are treated in a user friendly way, accepting and processing multiple versions. A new development is the use of spacetime objects for subsequent processing.

Sockeye: A 3D Environment for Comparative Genomics

PubMed Central

Montgomery, Stephen B.; Astakhova, Tamara; Bilenky, Mikhail; Birney, Ewan; Fu, Tony; Hassel, Maik; Melsopp, Craig; Rak, Marcin; Robertson, A. Gordon; Sleumer, Monica; Siddiqui, Asim S.; Jones, Steven J.M.

2004-01-01

Comparative genomics techniques are used in bioinformatics analyses to identify the structural and functional properties of DNA sequences. As the amount of available sequence data steadily increases, the ability to perform large-scale comparative analyses has become increasingly relevant. In addition, the growing complexity of genomic feature annotation means that new approaches to genomic visualization need to be explored. We have developed a Java-based application called Sockeye that uses three-dimensional (3D) graphics technology to facilitate the visualization of annotation and conservation across multiple sequences. This software uses the Ensembl database project to import sequence and annotation information from several eukaryotic species. A user can additionally import their own custom sequence and annotation data. Individual annotation objects are displayed in Sockeye by using custom 3D models. Ensembl-derived and imported sequences can be analyzed by using a suite of multiple and pair-wise alignment algorithms. The results of these comparative analyses are also displayed in the 3D environment of Sockeye. By using the Java3D API to visualize genomic data in a 3D environment, we are able to compactly display cross-sequence comparisons. This provides the user with a novel platform for visualizing and comparing genomic feature organization. PMID:15123592

Further Evaluations of Functional Communication Training and Chained Schedules of Reinforcement to Treat Multiple Functions of Challenging Behavior

ERIC Educational Resources Information Center

Falcomata, Terry S.; Muething, Colin S.; Gainey, Summer; Hoffman, Katherine; Fragale, Christina

2013-01-01

We evaluated functional communication training (FCT) combined with a chained schedule of reinforcement procedure for the treatment of challenging behavior exhibited by two individuals diagnosed with Asperger syndrome and autism. Following functional analyses that suggested that challenging behavior served multiple functions for both participants,…

Using Evolution to Guide Protein Engineering: The Devil IS in the Details.

PubMed

Swint-Kruse, Liskin

2016-07-12

For decades, protein engineers have endeavored to reengineer existing proteins for novel applications. Overall, protein folds and gross functions can be readily transferred from one protein to another by transplanting large blocks of sequence (i.e., domain recombination). However, predictably fine-tuning function (e.g., by adjusting ligand affinity, specificity, catalysis, and/or allosteric regulation) remains a challenge. One approach has been to use the sequences of protein families to identify amino acid positions that change during the evolution of functional variation. The rationale is that these nonconserved positions could be mutated to predictably fine-tune function. Evolutionary approaches to protein design have had some success, but the engineered proteins seldom replicate the functional performances of natural proteins. This Biophysical Perspective reviews several complexities that have been revealed by evolutionary and experimental studies of protein function. These include 1) challenges in defining computational and biological thresholds that define important amino acids; 2) the co-occurrence of many different patterns of amino acid changes in evolutionary data; 3) difficulties in mapping the patterns of amino acid changes to discrete functional parameters; 4) the nonconventional mutational outcomes that occur for a particular group of functionally important, nonconserved positions; 5) epistasis (nonadditivity) among multiple mutations; and 6) the fact that a large fraction of a protein's amino acids contribute to its overall function. To overcome these challenges, new goals are identified for future studies. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Analysis of functional polymorphisms in three synaptic plasticity-related genes (BDNF, COMT AND UCHL1) in Alzheimer's disease in Colombia.

PubMed

Forero, Diego A; Benítez, Bruno; Arboleda, Gonzalo; Yunis, Juan J; Pardo, Rodrigo; Arboleda, Humberto

2006-07-01

In recent years, it has been proposed that synaptic dysfunction may be an important etiological factor for Alzheimer's disease (AD). This hypothesis has important implications for the analysis of AD genetic risk in case-control studies. In the present work, we analyzed common functional polymorphisms in three synaptic plasticity-related genes (brain-derived neurotrophic factor, BDNF Val66Met; catechol-O-methyl transferase, COMT Val158; ubiquitin carboxyl-terminal hydroxylase, UCHL1 S18Y) in a sample of 102 AD cases and 168 age and sex matched controls living in Bogotá, Colombia. There was not association between UCHL1 polymorphism and AD in our sample. We have found an initial association with BDNF polymorphism in familial cases and with COMT polymorphism in male and sporadic patients. These initial associations were lost after Bonferroni correction for multiple testing. Unadjusted results may be compatible with the expected functional effect of variations in these genes on pathological memory and cognitive dysfunction, as has been implicated in animal and cell models and also from neuropsychological analysis of normal subjects carriers of the AD associated genotypes. An exploration of functional variants in these and in other synaptic plasticity-related genes (a synaptogenomics approach) in independent larger samples will be important to discover new genes associated with AD.

Identification of multiple interacting alleles conferring low glycerol and high ethanol yield in Saccharomyces cerevisiae ethanolic fermentation

PubMed Central

2013-01-01

Background Genetic engineering of industrial microorganisms often suffers from undesirable side effects on essential functions. Reverse engineering is an alternative strategy to improve multifactorial traits like low glycerol/high ethanol yield in yeast fermentation. Previous rational engineering of this trait always affected essential functions like growth and stress tolerance. We have screened Saccharomyces cerevisiae biodiversity for specific alleles causing lower glycerol/higher ethanol yield, assuming higher compatibility with normal cellular functionality. Previous work identified ssk1E330N…K356N as causative allele in strain CBS6412, which displayed the lowest glycerol/ethanol ratio. Results We have now identified a unique segregant, 26B, that shows similar low glycerol/high ethanol production as the superior parent, but lacks the ssk1E330N…K356N allele. Using segregants from the backcross of 26B with the inferior parent strain, we applied pooled-segregant whole-genome sequence analysis and identified three minor quantitative trait loci (QTLs) linked to low glycerol/high ethanol production. Within these QTLs, we identified three novel alleles of known regulatory and structural genes of glycerol metabolism, smp1R110Q,P269Q, hot1P107S,H274Y and gpd1L164P as causative genes. All three genes separately caused a significant drop in the glycerol/ethanol production ratio, while gpd1L164P appeared to be epistatically suppressed by other alleles in the superior parent. The order of potency in reducing the glycerol/ethanol ratio of the three alleles was: gpd1L164P > hot1P107S,H274Y ≥ smp1R110Q,P269Q. Conclusions Our results show that natural yeast strains harbor multiple specific alleles of genes controlling essential functions, that are apparently compatible with survival in the natural environment. These newly identified alleles can be used as gene tools for engineering industrial yeast strains with multiple subtle changes, minimizing the risk of negatively affecting other essential functions. The gene tools act at the transcriptional, regulatory or structural gene level, distributing the impact over multiple targets and thus further minimizing possible side-effects. In addition, the results suggest polygenic analysis of complex traits as a promising new avenue to identify novel components involved in cellular functions, including those important in industrial applications. PMID:23759206

Contemporary approaches to modulating the nitric oxide-cGMP pathway in cardiovascular disease

PubMed Central

Kraehling, Jan R.; Sessa, William C.

2017-01-01

Endothelial cells lining the vessel wall control important aspects of vascular homeostasis. In particular, the production of endothelium-derived nitric oxide and activation of soluble guanylate cyclase promotes endothelial quiescence and governs vasomotor function and proportional remodeling of blood vessels. Here, we discuss novel approaches to improve endothelial nitric oxide generation and preserve its bioavailability. We also discuss therapeutic opportunities aimed at activation of soluble guanylate cyclase for multiple cardiovascular indications. PMID:28360348

Multiple-choice tests stabilize access to marginal knowledge.

PubMed

Cantor, Allison D; Eslick, Andrea N; Marsh, Elizabeth J; Bjork, Robert A; Bjork, Elizabeth Ligon

2015-02-01

Marginal knowledge refers to knowledge that is stored in memory, but is not accessible at a given moment. For example, one might struggle to remember who wrote The Call of the Wild, even if that knowledge is stored in memory. Knowing how best to stabilize access to marginal knowledge is important, given that new learning often requires accessing and building on prior knowledge. While even a single opportunity to restudy marginal knowledge boosts its later accessibility (Berger, Hall, & Bahrick, 1999), in many situations explicit relearning opportunities are not available. Our question is whether multiple-choice tests (which by definition expose the learner to the correct answers) can also serve this function and, if so, how testing compares to restudying given that tests can be particularly powerful learning devices (Roediger & Karpicke, 2006). In four experiments, we found that multiple-choice testing had the power to stabilize access to marginal knowledge, and to do so for at least up to a week. Importantly, such tests did not need to be paired with feedback, although testing was no more powerful than studying. Overall, the results support the idea that one's knowledge base is unstable, with individual pieces of information coming in and out of reach. The present findings have implications for a key educational challenge: ensuring that students have continuing access to information they have learned.

Myosin II Activity Softens Cells in Suspension.

PubMed

Chan, Chii J; Ekpenyong, Andrew E; Golfier, Stefan; Li, Wenhong; Chalut, Kevin J; Otto, Oliver; Elgeti, Jens; Guck, Jochen; Lautenschläger, Franziska

2015-04-21

The cellular cytoskeleton is crucial for many cellular functions such as cell motility and wound healing, as well as other processes that require shape change or force generation. Actin is one cytoskeleton component that regulates cell mechanics. Important properties driving this regulation include the amount of actin, its level of cross-linking, and its coordination with the activity of specific molecular motors like myosin. While studies investigating the contribution of myosin activity to cell mechanics have been performed on cells attached to a substrate, we investigated mechanical properties of cells in suspension. To do this, we used multiple probes for cell mechanics including a microfluidic optical stretcher, a microfluidic microcirculation mimetic, and real-time deformability cytometry. We found that nonadherent blood cells, cells arrested in mitosis, and naturally adherent cells brought into suspension, stiffen and become more solidlike upon myosin inhibition across multiple timescales (milliseconds to minutes). Our results hold across several pharmacological and genetic perturbations targeting myosin. Our findings suggest that myosin II activity contributes to increased whole-cell compliance and fluidity. This finding is contrary to what has been reported for cells attached to a substrate, which stiffen via active myosin driven prestress. Our results establish the importance of myosin II as an active component in modulating suspended cell mechanics, with a functional role distinctly different from that for substrate-adhered cells. Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Light and Dark of Reactive Oxygen Species for Vascular Function: 2014 ASVB (Asian Society of Vascular Biology).

PubMed

Shimokawa, Hiroaki; Satoh, Kimio

2015-05-01

Vascular-derived hydrogen peroxide (H2O2) serves as an important signaling molecule in the cardiovascular system and contributes to vascular homeostasis. H2O2 is a second messenger, transducing the oxidative signal into biological responses through posttranslational protein modification. The balance between oxidant and antioxidant systems regulates intracellular redox status, and their imbalance causes oxidative or reductive stress, leading to cellular damage in cardiovascular systems. Excessive H2O2 deteriorates vascular functions and promotes vascular disease through multiple pathways. The RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including production of excessive reactive oxygen species, leading to the development of cardiovascular diseases. Rho-kinase (ROCK1 and ROCK2) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. Rho-kinase plays a crucial role in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Thus, Rho-kinase inhibitors may be useful for the treatment of cardiovascular diseases in humans. In this review, we will briefly discuss the roles of vascular-derived H2O2 and review the recent progress in the translational research on the therapeutic importance of the Rho-kinase pathway in cardiovascular medicine.

Effects of Growth Factors on Dental Stem/ProgenitorCells

PubMed Central

Kim, Sahng G.; Solomon, Charles; Zheng, Ying; Suzuki, Takahiro; Mo, Chen; Song, Songhee; Jiang, Nan; Cho, Shoko; Zhou, Jian; Mao, Jeremy J.

2014-01-01

Synopsis The primary goal of regenerative endodontics is to restore the vitality and functions of the dentin-pulp complex, as opposed to filing of the root canal with bioinert materials. Structural restoration is also important but is likely secondary to vitality and functions. Myriads growth factors regulate multiple cellular functions including migration, proliferation, differentiation and apoptosis of several cell types that are intimately involved in dentin-pulp regeneration: odontoblasts, interstitial fibroblasts, vascular-endothelial cells and sprouting nerve fibers. Recent work showing that growth factor delivery, without cell transplantation, can yield pulp-dentin like tissues in vivo provides one of the tangible pathways for regenerative endodontics. This review synthesizes our knowledge on a multitude of growth factors that are known or anticipated to be efficacious in dental pulp-dentin regeneration. PMID:22835538

Lysophosphatidic Acid (LPA) Signaling in Human and Ruminant Reproductive Tract

PubMed Central

Wocławek-Potocka, Izabela; Rawińska, Paulina; Kowalczyk-Zieba, Ilona; Boruszewska, Dorota; Sinderewicz, Emilia; Waśniewski, Tomasz; Skarzynski, Dariusz Jan

2014-01-01

Lysophosphatidic acid (LPA) through activating its G protein-coupled receptors (LPAR 1–6) exerts diverse cellular effects that in turn influence several physiological processes including reproductive function of the female. Studies in various species of animals and also in humans have identified important roles for the receptor-mediated LPA signaling in multiple aspects of human and animal reproductive tract function. These aspects range from ovarian and uterine function, estrous cycle regulation, early embryo development, embryo implantation, decidualization to pregnancy maintenance and parturition. LPA signaling can also have pathological consequences, influencing aspects of endometriosis and reproductive tissue associated tumors. The review describes recent progress in LPA signaling research relevant to human and ruminant reproduction, pointing at the cow as a relevant model to study LPA influence on the human reproductive performance. PMID:24744506

Evolution of the Black Hole Mass Function in Star Clusters from Multiple Mergers

NASA Astrophysics Data System (ADS)

Christian, Pierre; Mocz, Philip; Loeb, Abraham

2018-05-01

We investigate the effects of black hole (BH) mergers in star clusters on the black hole mass function (BHMF). As BHs are not produced in pair-instability supernovae, it is suggested that there is a dearth of high-mass stellar BHs. This dearth generates a gap in the upper end of the BHMF. Meanwhile, parameter fitting of X-ray binaries suggests the existence of a gap in the mass function under 5 solar masses. We show, through evolving a coagulation equation, that BH mergers can appreciably fill the upper mass gap, and that the lower mass gap generates potentially observable features at larger mass scales. We also explore the importance of ejections in such systems and whether dynamical clusters can be formation sites of intermediate-mass BH seeds.

Novel insights of microRNAs in the development of systemic lupus erythematosus.

PubMed

Le, Xiong; Yu, Xiang; Shen, Nan

2017-09-01

To provide a brief overview of recent progress in microRNA biogenesis and homeostasis, its function in immune system and systemic lupus erythematosus (SLE), as well as successful microRNA-based therapy in vivo. Stepwise microRNA biogenesis is elaborately regulated at multiple levels, ranging from transcription to ultimate function. Mature microRNAs have inhibitory effects on various biological molecules, which are crucial for stabilizing and normalizing differentiation and function of immune cells. Abnormality in microRNA expression contributes to dysfunction of lupus immune cells and resident cells in local tissues. Manipulation of dysregulated microRNAs in vivo through microRNA delivery or targeting microRNA might be promising for SLE treatment. Recent advances highlight that microRNAs are important in immunity, lupus autoimmunity and as potential therapy target for SLE.

Introduction to the special section on "Hormones and cognition: perspectives, controversies, and challenges for future research".

PubMed

Frick, Karyn M

2012-02-01

The research of the past two decades has firmly established that hormones modulate numerous aspects of cognitive function, including memory, attention, decision-making, and sensory processing. That such a wide variety of hormones influence cognition mediated by multiple nonhypothalamic brain regions illustrates the critical importance of hormones to neural and cognitive function. The diversity of hormonal effects on cognition is evident in the collection of reviews and original research articles assembled for this special section. Together, these articles provide an overview of recent research on varied topics in hormones and cognition, address controversial issues in the field, and discuss challenges that must be overcome in future research to gain a better understanding of the mechanisms through which hormones modulate cognitive function.

Partners in crime: The role of tandem modules in gene transcription.

PubMed

Sharma, Rajal; Zhou, Ming-Ming

2015-09-01

Histones and their modifications play an important role in the regulation of gene transcription. Numerous modifications, such as acetylation, phosphorylation, methylation, ubiquitination, and SUMOylation, have been described. These modifications almost always co-occur and thereby increase the combinatorial complexity of post-translational modification detection. The domains that recognize these histone modifications often occur in tandem in the context of larger proteins and complexes. The presence of multiple modifications can positively or negatively regulate the binding of these tandem domains, influencing downstream cellular function. Alternatively, these tandem domains can have novel functions from their independent parts. Here we summarize structural and functional information known about major tandem domains and their histone binding properties. An understanding of these interactions is key for the development of epigenetic therapy. © 2015 The Protein Society.

The Hepatic Response to Thermal Injury: Is the Liver Important for Postburn Outcomes?

PubMed Central

Jeschke, Marc G

2009-01-01

Thermal injury produces a profound hypermetabolic and hypercatabolic stress response characterized by increased endogenous glucose production via gluconeogenesis and glycogenolysis, lipolysis, and proteolysis. The liver is the central body organ involved in these metabolic responses. It is suggested that the liver, with its metabolic, inflammatory, immune, and acute phase functions, plays a pivotal role in patient survival and recovery by modulating multiple pathways following thermal injury. Studies have evaluated the role and function of the liver during the postburn response and showed that liver integrity and function are essential for survival, and that hepatic acute phase proteins are strong predictors for postburn survival. This review discusses these studies and delineates the pivotal role of the liver in patients following severe thermal injury. PMID:19603107

Multiplicity distributions of charged hadrons in vp and charged current interactions

NASA Astrophysics Data System (ADS)

Jones, G. T.; Jones, R. W. L.; Kennedy, B. W.; Morrison, D. R. O.; Mobayyen, M. M.; Wainstein, S.; Aderholz, M.; Hantke, D.; Katz, U. F.; Kern, J.; Schmitz, N.; Wittek, W.; Borner, H. P.; Myatt, G.; Radojicic, D.; Burke, S.

1992-03-01

Using data on vp andbar vp charged current interactions from a bubble chamber experiment with BEBC at CERN, the multiplicity distributions of charged hadrons are investigated. The analysis is based on ˜20000 events with incident v and ˜10000 events with incidentbar v. The invariant mass W of the total hadronic system ranges from 3 GeV to ˜14 GeV. The experimental multiplicity distributions are fitted by the binomial function (for different intervals of W and in different intervals of the rapidity y), by the Levy function and the lognormal function. All three parametrizations give acceptable values for X 2. For fixed W, forward and backward multiplicities are found to be uncorrelated. The normalized moments of the charged multiplicity distributions are measured as a function of W. They show a violation of KNO scaling.

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.

Two roles of the context in Pavlovian fear conditioning.

PubMed

Urcelay, Gonzalo P; Miller, Ralph R

2010-04-01

At both empirical and theoretical levels, multiple functional roles of contextual information upon memory performance have been proposed without a clear dissociation of these roles. Some theories have assumed that contexts are functionally similar to cues, whereas other views emphasize the retrieval facilitating properties of contextual information. In Experiment 1, we observed that one critical parameter, the spacing of trials, could determine whether the context would function as a conditioned stimulus or as a retrieval cue for memories trained in different phases. Experiments 2 and 3 doubly dissociated these functions by selectively disrupting one role but not the other, and vice versa. Overall, these observations identify one determinant of different functions of contextual information and pose a major challenge to theories of learning that assume exclusively one or the other function of the context. Moreover, these data emphasize the importance of parametric variations on behavioral control, which has critical implications for studies designed to understand the role of the hippocampus in processing of contextual attributes.

The role of the cerebellum in the regulation of language functions.

PubMed

Starowicz-Filip, Anna; Chrobak, Adrian Andrzej; Moskała, Marek; Krzyżewski, Roger M; Kwinta, Borys; Kwiatkowski, Stanisław; Milczarek, Olga; Rajtar-Zembaty, Anna; Przewoźnik, Dorota

2017-08-29

The present paper is a review of studies on the role of the cerebellum in the regulation of language functions. This brain structure until recently associated chiefly with motor skills, visual-motor coordination and balance, proves to be significant also for cognitive functioning. With regard to language functions, studies show that the cerebellum determines verbal fluency (both semantic and formal) expressive and receptive grammar processing, the ability to identify and correct language mistakes, and writing skills. Cerebellar damage is a possible cause of aphasia or the cerebellar mutism syndrome (CMS). Decreased cerebellocortical connectivity as well as anomalies in the structure of the cerebellum are emphasized in numerous developmental dyslexia theories. The cerebellum is characterized by linguistic lateralization. From the neuroanatomical perspective, its right hemisphere and dentate nucleus, having multiple cerebellocortical connections with the cerebral cortical language areas, are particularly important for language functions. Usually, language deficits developed as a result of a cerebellar damage have subclinical intensity and require applying sensitive neuropsychological diagnostic tools designed to assess higher verbal functions.