Science.gov

Sample records for adjusted analysis revealed

  1. Adjustment to Divorce Through Transactional Analysis

    ERIC Educational Resources Information Center

    Morris, James D.; Prescott, Mary R.

    1976-01-01

    Transactional Analysis in a group facilitates adjustment to divorce. Two case histories highlight the value of TA in conceptualizing the problem areas of each individual and the changes during group therapy. (Author)

  2. Confirmatory Factor Analysis of Transfer Student Adjustment

    ERIC Educational Resources Information Center

    Young, Jacob T. N.; Litzler, Elizabeth

    2013-01-01

    Transfer students' adjustment to college has received substantial attention by researchers. This focus has predominately investigated the observation of "transfer shock": a decrease in grade point average (GPA) experienced after transferring. In response to the persistent focus on transfer shock, growing attention has been directed…

  3. An Analysis of P-3 Aircraft Service Period Adjustment Criteria

    DTIC Science & Technology

    1986-12-01

    A. ASPA(AIRCRAFT SERVICE PERIOD ADJUSTMENT) ....... 29 B. A REVIEW OF ANALYSIS METHODS ................... 310 1. Delphi ...uncertainty. A brief review of their procedures, advantages, and disadvantages is helpful to justify selecting the most appropriate method. 1. Delphi ...Technique The+ Delphi Technique is a method of statistically refining tie opinions of a group of experts or especially knowledgeable personnel. The

  4. Anticipatory postural adjustments to arm movement reveal complex control of paraspinal muscles in the thorax.

    PubMed

    Lee, Linda-Joy; Coppieters, Michel W; Hodges, Paul W

    2009-02-01

    Anatomical and empirical data suggest that deep and superficial muscles may have different functions for thoracic spine control. This study investigated thoracic paraspinal muscle activity during anticipatory postural adjustments associated with arm movement. Electromyographic (EMG) recordings were made from the right deep (multifidus/rotatores) and superficial (longissimus) muscles at T5, T8, and T11 levels using fine-wire electrodes. Ten healthy participants performed fast unilateral and bilateral flexion and extension arm movements in response to a light. EMG amplitude was measured during 25ms epochs for 150ms before and 400ms after deltoid EMG onset. During arm flexion movements, multifidus and longissimus had two bursts of activity, one burst prior to deltoid and a late burst. With arm extension both muscles were active in a single burst after deltoid onset. There was differential activity with respect to direction of trunk rotation induced by arm movement. Right longissimus was most active with left arm movements and right multifidus was most active with right arm movements. All levels of the thorax responded similarly. We suggest that although thoracic multifidus and longissimus function similarly to control sagittal plane perturbations, these muscles are differentially active with rotational forces on the trunk.

  5. Revealing Student Teacher's Thinking through Dilemma Analysis

    ERIC Educational Resources Information Center

    Talanquer, Vicente; Tomanek, Debra; Novodvorsky, Ingrid

    2007-01-01

    We explore the potential of dilemma analysis as an assessment tool to reveal student teachers' thinking and concerns about their practice. For this purpose we analyze the dilemma analyses completed by 22 student teachers enrolled in our science teacher preparation program over a period of four semesters. Student teachers' dilemmas fall into two…

  6. Molecular Isotopic Distribution Analysis (MIDAs) with Adjustable Mass Accuracy

    NASA Astrophysics Data System (ADS)

    Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo

    2014-01-01

    In this paper, we present Molecular Isotopic Distribution Analysis (MIDAs), a new software tool designed to compute molecular isotopic distributions with adjustable accuracies. MIDAs offers two algorithms, one polynomial-based and one Fourier-transform-based, both of which compute molecular isotopic distributions accurately and efficiently. The polynomial-based algorithm contains few novel aspects, whereas the Fourier-transform-based algorithm consists mainly of improvements to other existing Fourier-transform-based algorithms. We have benchmarked the performance of the two algorithms implemented in MIDAs with that of eight software packages (BRAIN, Emass, Mercury, Mercury5, NeutronCluster, Qmass, JFC, IC) using a consensus set of benchmark molecules. Under the proposed evaluation criteria, MIDAs's algorithms, JFC, and Emass compute with comparable accuracy the coarse-grained (low-resolution) isotopic distributions and are more accurate than the other software packages. For fine-grained isotopic distributions, we compared IC, MIDAs's polynomial algorithm, and MIDAs's Fourier transform algorithm. Among the three, IC and MIDAs's polynomial algorithm compute isotopic distributions that better resemble their corresponding exact fine-grained (high-resolution) isotopic distributions. MIDAs can be accessed freely through a user-friendly web-interface at http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/midas/index.html.

  7. Cells deficient in base-excision repair reveal cancer hallmarks originating from adjustments to genetic instability.

    PubMed

    Markkanen, Enni; Fischer, Roman; Ledentcova, Marina; Kessler, Benedikt M; Dianov, Grigory L

    2015-04-20

    Genetic instability, provoked by exogenous mutagens, is well linked to initiation of cancer. However, even in unstressed cells, DNA undergoes a plethora of spontaneous alterations provoked by its inherent chemical instability and the intracellular milieu. Base excision repair (BER) is the major cellular pathway responsible for repair of these lesions, and as deficiency in BER activity results in DNA damage it has been proposed that it may trigger the development of sporadic cancers. Nevertheless, experimental evidence for this model remains inconsistent and elusive. Here, we performed a proteomic analysis of BER deficient human cells using stable isotope labelling with amino acids in cell culture (SILAC), and demonstrate that BER deficiency, which induces genetic instability, results in dramatic changes in gene expression, resembling changes found in many cancers. We observed profound alterations in tissue homeostasis, serine biosynthesis, and one-carbon- and amino acid metabolism, all of which have been identified as cancer cell 'hallmarks'. For the first time, this study describes gene expression changes characteristic for cells deficient in repair of endogenous DNA lesions by BER. These expression changes resemble those observed in cancer cells, suggesting that genetically unstable BER deficient cells may be a source of pre-cancerous cells.

  8. Revealing Student Teachers' Thinking through Dilemma Analysis

    NASA Astrophysics Data System (ADS)

    Talanquer, Vicente; Tomanek, Debra; Novodvorsky, Ingrid

    2007-06-01

    We explore the potential of dilemma analysis as an assessment tool to reveal student teachers’ thinking and concerns about their practice. For this purpose we analyze the dilemma analyses completed by 22 student teachers enrolled in our science teacher preparation program over a period of four semesters. Student teachers’ dilemmas fall into two main groups: dilemmas about student performance and dilemmas associated with instructional decisions. These dilemmas reveal a variety of concerns that student teachers have about their work. In particular, concerns about lack of student motivation and its consequences on performance and instruction play a central role in student teachers’ thinking. The recognition of common patterns of thought in our student teacher thinking has made us reflect on and re-evaluate important components of the curriculum in our science teacher preparation program.

  9. Children’s Sleep and Adjustment: A Residualized Change Analysis

    PubMed Central

    El-Sheikh, Mona; Bub, Kristen L.; Kelly, Ryan J.; Buckhalt, Joseph A.

    2012-01-01

    We investigated longitudinal relations between children’s sleep and symptoms of depression, anxiety, and anger/aggression. We expected that initial sleep problems and increases in these problems over time would be associated with worse adjustment outcomes. The study had three waves with one year lags. At T1, 128 girls and 123 boys (M age = 8.23 years, SD = 0.73) participated; M ages at T2 and T3 = 9.31 years (SD = 0.79) and 10.28 (SD = 0.99). The sample was diverse in relation to economic adversity and ethnicity (66% European and 34% African American). Higher initial levels and increases in sleep/wake problems or sleepiness over three years predicted higher levels of depression and anxiety symptoms at T3, controlling for T1 levels. These associations were more pronounced for girls, African-American children, and children from lower SES homes. Findings build on a small body of literature addressing links between sleep and adjustment longitudinally and highlight the importance of adequate sleep for children’s optimal development, especially within the broader sociocultural milieu. PMID:23025266

  10. Genetic and Environmental Components of Adolescent Adjustment and Parental Behavior: A Multivariate Analysis

    ERIC Educational Resources Information Center

    Loehlin, John C.; Neiderhiser, Jenae M.; Reiss, David

    2005-01-01

    Adolescent adjustment measures may be related to each other and to the social environment in various ways. Are these relationships similar in genetic and environmental sources of covariation, or different? A multivariate behaviorgenetic analysis was made of 6 adjustment and 3 treatment composites from the study Nonshared Environment in Adolescent…

  11. Phosphoproteome Dynamics Upon Changes in Plant Water Status Reveal Early Events Associated With Rapid Growth Adjustment in Maize Leaves*

    PubMed Central

    Bonhomme, Ludovic; Valot, Benoît; Tardieu, François; Zivy, Michel

    2012-01-01

    Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in

  12. Phosphoproteome dynamics upon changes in plant water status reveal early events associated with rapid growth adjustment in maize leaves.

    PubMed

    Bonhomme, Ludovic; Valot, Benoît; Tardieu, François; Zivy, Michel

    2012-10-01

    Plant growth adjustment during water deficit is a crucial adaptive response. The rapid fine-tuned control achieved at the post-translational level is believed to be of considerable importance for regulating early changes in plant growth reprogramming. Aiming at a better understanding of early responses to contrasting plant water statuses, we carried out a survey of the protein phosphorylation events in the growing zone of maize leaves upon a range of water regimes. In this study, the impact of mild and severe water deficits were evaluated in comparison with constant optimal watering and with recovery periods lasting 5, 10, 20, 30, 45, and 60 min. Using four biological replicates per treatment and a robust quantitative phosphoproteomic methodology based on stable-isotope labeling, we identified 3664 unique phosphorylation sites on 2496 proteins. The abundance of nearly 1250 phosphorylated peptides was reproducibly quantified and profiled with high confidence among treatments. A total of 138 phosphopeptides displayed highly significant changes according to water regimes and enabled to identify specific patterns of response to changing plant water statuses. Further quantification of protein amounts emphasized that most phosphorylation changes did not reflect protein abundance variation. During water deficit and recovery, extensive changes in phosphorylation status occurred in critical regulators directly or indirectly involved in plant growth and development. These included proteins influencing epigenetic control, gene expression, cell cycle-dependent processes and phytohormone-mediated responses. Some of the changes depended on stress intensity whereas others depended on rehydration duration, including rapid recoveries that occurred as early as 5 or 10 mins after rewatering. By combining a physiological approach and a quantitative phosphoproteomic analysis, this work provides new insights into the in vivo early phosphorylation events triggered by rapid changes in

  13. Adjusting game difficulty level through Formal Concept Analysis

    NASA Astrophysics Data System (ADS)

    Gómez-Martín, Marco A.; Gómez-Martín, Pedro P.; Gonzâlez-Calero, Pedro A.; Díaz-Agudo, Belén

    In order to reach as many players as possible, videogames usually allow the user to choose the difficulty level. To do it, game designers have to decide the values that some game parameters will have depending on that decision. In simple videogames this is almost trivial: minesweeper is harder with longer board sizes and number of mines. In more complex games, game designers may take advantage of data mining to establish which of all the possible parameters will affect positively to the player experience. This paper describes the use of Formal Concept Analysis to help to balance the game using the logs obtained in the tests made prior the release of the game.

  14. Quantitative interactome analysis reveals a chemoresistant edgotype

    PubMed Central

    Chavez, Juan D.; Schweppe, Devin K.; Eng, Jimmy K.; Zheng, Chunxiang; Taipale, Alex; Zhang, Yiyi; Takara, Kohji; Bruce, James E.

    2015-01-01

    Chemoresistance is a common mode of therapy failure for many cancers. Tumours develop resistance to chemotherapeutics through a variety of mechanisms, with proteins serving pivotal roles. Changes in protein conformations and interactions affect the cellular response to environmental conditions contributing to the development of new phenotypes. The ability to understand how protein interaction networks adapt to yield new function or alter phenotype is limited by the inability to determine structural and protein interaction changes on a proteomic scale. Here, chemical crosslinking and mass spectrometry were employed to quantify changes in protein structures and interactions in multidrug-resistant human carcinoma cells. Quantitative analysis of the largest crosslinking-derived, protein interaction network comprising 1,391 crosslinked peptides allows for ‘edgotype' analysis in a cell model of chemoresistance. We detect consistent changes to protein interactions and structures, including those involving cytokeratins, topoisomerase-2-alpha, and post-translationally modified histones, which correlate with a chemoresistant phenotype. PMID:26235782

  15. Social support and adjustment to caring for elder family members: A multi-study analysis.

    PubMed

    Smerglia, Virginia L; Miller, Nancy B; Sotnak, Diane L; Geiss, Carrie A

    2007-03-01

    This multi-study analysis systematically examines research findings on relationships between social support and caregiver adjustment to discover whether informal support helps family caregivers. Caring for older relatives is an ongoing stressful life course event and role. Informal social support is often used as a predictor of caregiver adjustment outcomes. It is widely believed to enhance adjustment. Yet the varied research results do not necessarily support this belief. A computer-generated literature search of social sciences and medical databases produced thirty-five caregiving articles, published in refereed journals, which meet study parameters. A coding form was developed to categorize social support and adjustment variables for cross-tabular analyses. The findings show most relationships (61%) between social support and caregiver adjustment are not positively significant. Of the minority of positively significant relationships, neither perceived (available) nor received support is more important and neither instrumental nor socioemotional support is more likely to aid adjustment. Researchers and health care professionals need to explore the negative impact of social support and attributes of caregiver-care recipient relationships.

  16. Do insurers respond to risk adjustment? A long-term, nationwide analysis from Switzerland.

    PubMed

    von Wyl, Viktor; Beck, Konstantin

    2016-03-01

    Community rating in social health insurance calls for risk adjustment in order to eliminate incentives for risk selection. Swiss risk adjustment is known to be insufficient, and substantial risk selection incentives remain. This study develops five indicators to monitor residual risk selection. Three indicators target activities of conglomerates of insurers (with the same ownership), which steer enrollees into specific carriers based on applicants' risk profiles. As a proxy for their market power, those indicators estimate the amount of premium-, health care cost-, and risk-adjustment transfer variability that is attributable to conglomerates. Two additional indicators, derived from linear regression, describe the amount of residual cost differences between insurers that are not covered by risk adjustment. All indicators measuring conglomerate-based risk selection activities showed increases between 1996 and 2009, paralleling the establishment of new conglomerates. At their maxima in 2009, the indicator values imply that 56% of the net risk adjustment volume, 34% of premium variability, and 51% cost variability in the market were attributable to conglomerates. From 2010 onwards, all indicators decreased, coinciding with a pre-announced risk adjustment reform implemented in 2012. Likewise, the regression-based indicators suggest that the volume and variance of residual cost differences between insurers that are not equaled out by risk adjustment have decreased markedly since 2009 as a result of the latest reform. Our analysis demonstrates that risk-selection, especially by conglomerates, is a real phenomenon in Switzerland. However, insurers seem to have reduced risk selection activities to optimize their losses and gains from the latest risk adjustment reform.

  17. Applied Behavior Analysis Programs for Autism: Sibling Psychosocial Adjustment during and Following Intervention Use

    ERIC Educational Resources Information Center

    Cebula, Katie R.

    2012-01-01

    Psychosocial adjustment in siblings of children with autism whose families were using a home-based, applied behavior analysis (ABA) program was compared to that of siblings in families who were not using any intensive autism intervention. Data gathered from parents, siblings and teachers indicated that siblings in ABA families experienced neither…

  18. On the geometric analysis and adjustment of optical satellite observations. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Tsimis, E.

    1972-01-01

    Satellite geodesy methods were catagorized into three divisions: geometric, dynamic, and mixed. These catagories furnish the basis for distinction between geometric and dynamic satellite geodesy. The dual adjustment, geometric analysis, and Cartesian coodinate determination are examined for two observing stations. Similar illustrations are given when more than two observing stations are used.

  19. Children's Responses to Interparental Conflict: A Meta-Analysis of Their Associations with Child Adjustment

    ERIC Educational Resources Information Center

    Rhoades, Kimberly A.

    2008-01-01

    A meta-analysis examined the relations between children's adjustment and children's cognitive, affective, behavioral, and physiological responses to interparental conflict. Studies included children between 5 and 19 years of age. Moderate effect sizes were found for the associations between cognitions and internalizing and externalizing behavior…

  20. Parents' psychological adjustment in families of children with Spina Bifida: a meta-analysis

    PubMed Central

    Vermaes, Ignace PR; Janssens, Jan MAM; Bosman, Anna MT; Gerris, Jan RM

    2005-01-01

    Background Spina Bifida (SB) is the second most common birth defect worldwide. Since the chances of survival in children with severe SB-forms have increased, medical care has shifted its emphasis from life-saving interventions to fostering the quality of life for these children and their families. Little is known, however, about the impact of SB on family adjustment. Reviewers have struggled to synthesize the few contradictory studies available. In this systematic review a new attempt was made to summarize the findings by using meta-analysis and by delimiting the scope of review to one concept of family adjustment: Parents' psychological adjustment. The questions addressed were: (a) do parents of children with SB have more psychological distress than controls? (b) do mothers and fathers differ? and (c) which factors correlate with variations in psychological adjustment? Methods PsycInfo, Medline, and reference lists were scanned. Thirty-three relevant studies were identified of which 15 were eligible for meta-analysis. Results SB had a negative medium-large effect on parents' psychological adjustment. The effect was more heterogeneous for mothers than for fathers. In the reviewed studies child factors (age, conduct problems, emotional problems, and mental retardation), parent factors (SES, hope, appraised stress, coping, and parenting competence), family factors (family income, partner relationship, and family climate), and environmental factors (social support) were found to be associated with variations in parents' psychological adjustment. Conclusion Meta-analysis proved to be helpful in organizing studies. Clinical implications indicate a need to be especially alert to psychological suffering in mothers of children with SB. Future research should increase sample sizes through multi-center collaborations. PMID:16120229

  1. School adjustment of children in residential care: a multi-source analysis.

    PubMed

    Martín, Eduardo; Muñoz de Bustillo, María del Carmen

    2009-11-01

    School adjustment is one the greatest challenges in residential child care programs. This study has two aims: to analyze school adjustment compared to a normative population, and to carry out a multi-source analysis (child, classmates, and teacher) of this adjustment. A total of 50 classrooms containing 60 children from residential care units were studied. The "Método de asignación de atributos perceptivos" (Allocation of perceptive attributes; Díaz-Aguado, 2006), the "Test Autoevaluativo Multifactorial de Adaptación Infantil" (TAMAI [Multifactor Self-assessment Test of Child Adjustment]; Hernández, 1996) and the "Protocolo de valoración para el profesorado (Evaluation Protocol for Teachers; Fernández del Valle, 1998) were applied. The main results indicate that, compared with their classmates, children in residential care are perceived as more controversial and less integrated at school, although no differences were observed in problems of isolation. The multi-source analysis shows that there is agreement among the different sources when the externalized and visible aspects are evaluated. These results are discussed in connection with the practices that are being developed in residential child care programs.

  2. Comparison of conditional bias-adjusted estimators for interim analysis in clinical trials with survival data.

    PubMed

    Shimura, Masashi; Gosho, Masahiko; Hirakawa, Akihiro

    2017-02-17

    Group sequential designs are widely used in clinical trials to determine whether a trial should be terminated early. In such trials, maximum likelihood estimates are often used to describe the difference in efficacy between the experimental and reference treatments; however, these are well known for displaying conditional and unconditional biases. Established bias-adjusted estimators include the conditional mean-adjusted estimator (CMAE), conditional median unbiased estimator, conditional uniformly minimum variance unbiased estimator (CUMVUE), and weighted estimator. However, their performances have been inadequately investigated. In this study, we review the characteristics of these bias-adjusted estimators and compare their conditional bias, overall bias, and conditional mean-squared errors in clinical trials with survival endpoints through simulation studies. The coverage probabilities of the confidence intervals for the four estimators are also evaluated. We find that the CMAE reduced conditional bias and showed relatively small conditional mean-squared errors when the trials terminated at the interim analysis. The conditional coverage probability of the conditional median unbiased estimator was well below the nominal value. In trials that did not terminate early, the CUMVUE performed with less bias and an acceptable conditional coverage probability than was observed for the other estimators. In conclusion, when planning an interim analysis, we recommend using the CUMVUE for trials that do not terminate early and the CMAE for those that terminate early. Copyright © 2017 John Wiley & Sons, Ltd.

  3. Applied behavior analysis programs for autism: sibling psychosocial adjustment during and following intervention use.

    PubMed

    Cebula, Katie R

    2012-05-01

    Psychosocial adjustment in siblings of children with autism whose families were using a home-based, applied behavior analysis (ABA) program was compared to that of siblings in families who were not using any intensive autism intervention. Data gathered from parents, siblings and teachers indicated that siblings in ABA families experienced neither significant drawbacks nor benefits in terms of their behavioral adjustment, sibling relationship quality and self-concept compared to control group siblings, either during or following intervention use. Parents and siblings perceived improvements in sibling interaction since the outset of ABA, with parents somewhat more positive in their views than were siblings. Social support was associated with better sibling outcomes in all groups. Implications for supporting families using ABA are considered.

  4. Detailed analysis of charge transport in amorphous organic thin layer by multiscale simulation without any adjustable parameters

    PubMed Central

    Uratani, Hiroki; Kubo, Shosei; Shizu, Katsuyuki; Suzuki, Furitsu; Fukushima, Tatsuya; Kaji, Hironori

    2016-01-01

    Hopping-type charge transport in an amorphous thin layer composed of organic molecules is simulated by the combined use of molecular dynamics, quantum chemical, and Monte Carlo calculations. By explicitly considering the molecular structure and the disordered intermolecular packing, we reasonably reproduce the experimental hole and electron mobilities and their applied electric field dependence (Poole–Frenkel behaviour) without using any adjustable parameters. We find that the distribution of the density-of-states originating from the amorphous nature has a significant impact on both the mobilities and Poole–Frenkel behaviour. Detailed analysis is also provided to reveal the molecular-level origin of the charge transport, including the origin of Poole–Frenkel behaviour. PMID:28000728

  5. Detailed analysis of charge transport in amorphous organic thin layer by multiscale simulation without any adjustable parameters

    NASA Astrophysics Data System (ADS)

    Uratani, Hiroki; Kubo, Shosei; Shizu, Katsuyuki; Suzuki, Furitsu; Fukushima, Tatsuya; Kaji, Hironori

    2016-12-01

    Hopping-type charge transport in an amorphous thin layer composed of organic molecules is simulated by the combined use of molecular dynamics, quantum chemical, and Monte Carlo calculations. By explicitly considering the molecular structure and the disordered intermolecular packing, we reasonably reproduce the experimental hole and electron mobilities and their applied electric field dependence (Poole–Frenkel behaviour) without using any adjustable parameters. We find that the distribution of the density-of-states originating from the amorphous nature has a significant impact on both the mobilities and Poole–Frenkel behaviour. Detailed analysis is also provided to reveal the molecular-level origin of the charge transport, including the origin of Poole–Frenkel behaviour.

  6. Design and Stress Analysis of Low-Noise Adjusted Bearing Contact Spiral Bevel Gears

    NASA Technical Reports Server (NTRS)

    Litvin, Faydor L.; Fuentes, Alfonso; Mullins, Baxter R.; Woods, Ron

    2002-01-01

    An integrated computerized approach for design and stress analysis of low-noise spiral bevel gear drives with adjusted bearing contact has been developed. The computation procedure is an iterative process, requiring four separate steps that provide: (a) a parabolic function of transmission errors that is able to reduce the effect of errors of alignment, and (b) reduction of the shift of bearing contact caused by misalignment. Application of finite element analysis permits the contact and bending stresses to be determined and investigate the formation of the bearing contact. The design of finite element models and boundary conditions is automated and does not require an intermediate CAD computer program. A commercially available finite element analysis computer program with contact capability was used to conduct the stress analysis. The theory developed is illustrated with numerical examples.

  7. Early adolescent friendships and academic adjustment: examining selection and influence processes with longitudinal social network analysis.

    PubMed

    Shin, Huiyoung; Ryan, Allison M

    2014-11-01

    This study investigated early adolescent friendship selection and social influence with regard to academic motivation (self-efficacy and intrinsic value), engagement (effortful and disruptive behavior), and achievement (GPA calculated from report card grades) among 6th graders (N = 587, 50% girls at Wave 1; N = 576, 52% girls at Wave 2) followed from fall to spring within 1 academic year. A stochastic actor-based model of social network analysis was used to overcome methodological limitations of prior research on friends, peer groups, and academic adjustment. Evidence that early adolescents sought out friends who were similar to themselves (selection) was found in regard to academic self-efficacy, and a similar trend was found for achievement. Evidence that friends became more similar to their friends over time (influence) was found for all aspects of academic adjustment except academic self-efficacy. Collectively, results indicate that selection effects were not as pervasive as influence effects in explaining similarity among friends in academic adjustment. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  8. Design and Stress Analysis of Low-Noise Adjusted Bearing Contact Spiral Bevel Gears

    NASA Technical Reports Server (NTRS)

    Fuentes, A.; Litvin, F. L.; Mullins, B. R.; Woods, R.; Handschuh, R. F.; Lewicki, David G.

    2002-01-01

    An integrated computerized approach for design and stress analysis of low-noise spiral bevel gear drives with adjusted bearing contact is proposed. The procedure of computations is an iterative process that requires four separate procedures and provide: (a) a parabolic function of transmission errors that is able to reduce the effect of errors of alignment on noise and vibration, and (b) reduction of the shift of bearing contact caused by misalignment. Application of finite element analysis enables us to determine the contact and bending stresses and investigate the formation of the bearing contact. The design of finite element models and boundary conditions is automated and does not require intermediate CAD computer programs for application of general purpose computer program for finite element analysis.

  9. Partner's adjustment to breast cancer: a critical analysis of intervention studies.

    PubMed

    Cochrane, Barbara B; Lewis, Frances Marcus

    2005-05-01

    Partners of breast cancer patients do not have resources available for dealing with their concerns. An analysis of intervention studies with partners was conducted, spanning research published from 1966 to 2004. Although there is considerable descriptive research documenting the need for partner interventions in the context of breast cancer, only 4 studies met criteria for inclusion in this analysis. Two studies reported limited intervention efficacy, but none incorporated all characteristics of a rigorous clinical trial with adequate power to fully test the intervention. Future intervention research should incorporate randomized, controlled clinical trial designs; have adequate statistical power; clearly report eligibility criteria; delineate theoretically based, fully explicated, and consistently delivered interventions; and use outcome measures that are sensitive to empirically derived partner-adjustment issues.

  10. Skart: A skewness- and autoregression-adjusted batch-means procedure for simulation analysis

    NASA Astrophysics Data System (ADS)

    Tafazzoli Yazdi, Ali

    We discuss Skart, an automated batch-means procedure for constructing a skewness- and autoregression-adjusted confidence interval (CI) for the steady-state mean of a simulation output process in either discrete time (i.e., observation-based statistics) or continuous time (i.e., time-persistent statistics). Skart is a sequential procedure designed to deliver a CI that satisfies user-specified requirements concerning not only the CI's coverage probability but also the absolute or relative precision provided by its half-length. Skart exploits separate adjustments to the half-length of the classical batchmeans CI so as to account for the effects on the distribution of the underlying Student's t-statistic that arise from skewness (nonnormality) and autocorrelation of the batch means. The skewness adjustment is based on a modified Cornish-Fisher expansion for the classical batch-means Student's t -ratio, and the autocorrelation adjustment is based on an autoregressive approximation to the batch-means process for sufficiently large batch sizes. Skart also delivers a point estimator for the steady-state mean that is approximately free of initialization bias. The duration of the associated warm-up period (i.e., the statistics clearing time) is based on iteratively applying von Neumann's randomness test to spaced batch means with progressively increasing batch sizes and interbatch spacer sizes. In an experimental performance evaluation involving a wide range of test processes, Skart compared favorably with other simulation analysis methods---namely, its predecessors ASAP3, WASSP, and SBatch as well as ABATCH, LBATCH, the Heidelberger-Welch procedure, and the Law-Carson procedure. Specifically, Skart exhibited competitive sampling efficiency and substantially closer conformance to the given CI coverage probabilities than the other procedures. Also presented is a nonsequential version of Skart, called N-Skart, in which the user supplies a single simulation-generated series of

  11. Links between patterns of racial socialization and discrimination experiences and psychological adjustment: a cluster analysis.

    PubMed

    Ajayi, Alex A; Syed, Moin

    2014-10-01

    This study used a person-oriented analytic approach to identify meaningful patterns of barriers-focused racial socialization and perceived racial discrimination experiences in a sample of 295 late adolescents. Using cluster analysis, three distinct groups were identified: Low Barrier Socialization-Low Discrimination, High Barrier Socialization-Low Discrimination, and High Barrier Socialization-High Discrimination clusters. These groups were substantively unique in terms of the frequency of racial socialization messages about bias preparation and out-group mistrust its members received and their actual perceived discrimination experiences. Further, individuals in the High Barrier Socialization-High Discrimination cluster reported significantly higher depressive symptoms than those in the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. However, no differences in adjustment were observed between the Low Barrier Socialization-Low Discrimination and High Barrier Socialization-Low Discrimination clusters. Overall, the findings highlight important individual differences in how young people of color experience their race and how these differences have significant implications on psychological adjustment.

  12. A Third Moment Adjusted Test Statistic for Small Sample Factor Analysis.

    PubMed

    Lin, Johnny; Bentler, Peter M

    2012-01-01

    Goodness of fit testing in factor analysis is based on the assumption that the test statistic is asymptotically chi-square; but this property may not hold in small samples even when the factors and errors are normally distributed in the population. Robust methods such as Browne's asymptotically distribution-free method and Satorra Bentler's mean scaling statistic were developed under the presumption of non-normality in the factors and errors. This paper finds new application to the case where factors and errors are normally distributed in the population but the skewness of the obtained test statistic is still high due to sampling error in the observed indicators. An extension of Satorra Bentler's statistic is proposed that not only scales the mean but also adjusts the degrees of freedom based on the skewness of the obtained test statistic in order to improve its robustness under small samples. A simple simulation study shows that this third moment adjusted statistic asymptotically performs on par with previously proposed methods, and at a very small sample size offers superior Type I error rates under a properly specified model. Data from Mardia, Kent and Bibby's study of students tested for their ability in five content areas that were either open or closed book were used to illustrate the real-world performance of this statistic.

  13. A Latent Class Analysis of Maternal Depressive Symptoms over 12 Years and Offspring Adjustment in Adolescence

    PubMed Central

    Campbell, Susan B.; Morgan-Lopez, Antonio A.; Cox, Martha J.; McLoyd, Vonnie C.

    2009-01-01

    We used data from the NICHD Study of Early Child Care and Youth Development and latent class analysis to model patterns of maternal depressive symptoms from infant age 1 month to the transition to adolescence (age 12), and then examined adolescent adjustment at age 15 as a function of the course and severity of maternal symptoms. We identified five latent classes of symptoms in these 1357 women while also taking into account sociodemographic measures: never depressed; stable subclinical; early-decreasing; moderately elevated; chronic. Women with few symptoms were more likely to be married, better educated, and in better physical health than women with more elevated symptoms. Family size and whether the pregnancy was planned also differentiated among classes. At age 15, adolescents whose mothers were in the chronic, elevated, and stable subclinical latent classes reported more internalizing and externalizing problems and acknowledged engaging in more risky behavior than did children of never-depressed mothers. Latent class differences in self-reported loneliness and dysphoria were also found. Finally, several significant interactions between sex and latent class suggested that girls whose mothers reported elevated symptoms of depression over time experienced more internalizing distress and dysphoric mood relative to their male counterparts. Discussion focuses on adolescent adjustment, especially among offspring whose mothers report stable symptoms of depression across their childhoods. PMID:19685946

  14. Invoking Thomas Kuhn: What Citation Analysis Reveals about Science Education

    NASA Astrophysics Data System (ADS)

    Loving, Cathleen C.; Cobern, William W.

    This paper analyzes how Thomas Kuhn's writings are used by others, especially science education researchers. Previous research in citation analysis is used to frame questions related to who cites Kuhn, in what manner and why. Research questions first focus on the variety of disciplines invoking Kuhn and to what extent Structure of Scientific Revolutions (SSR) is cited. The Web of Science database provides material from 1982 for this analysis. The science education literature is analyzed using back issues from 1985 of the Journal of Research in Science Teaching and Science Education. An article analysis reveals trends in terms of what Kuhnian ideas are most frequently invoked. Results indicate a wide array of disciplines from beekeeping to law cite Kuhn - especially generic citations to SSR. The science education journal analysis reveals pervasive use of the term paradigm, although use is quite varied. The two areas of research in science education most impacted by Kuhn appear to be conceptual change theory and constructivist epistemologies. Additional uses of Kuhn are discussed. The degree to which Kuhn is invoked in ways supporting the theoretical framework of citation analysis, whether his work is misappropriated, and the impact of Kuhn are discussed.

  15. Adjustment for population stratification via principal components in association analysis of rare variants.

    PubMed

    Zhang, Yiwei; Guan, Weihua; Pan, Wei

    2013-01-01

    For unrelated samples, principal component (PC) analysis has been established as a simple and effective approach to adjusting for population stratification in association analysis of common variants (CVs, with minor allele frequencies MAF > 5%). However, it is less clear how it would perform in analysis of low-frequency variants (LFVs, MAF between 1% and 5%), or of rare variants (RVs, MAF < 5%). Furthermore, with next-generation sequencing data, it is unknown whether PCs should be constructed based on CVs, LFVs, or RVs. In this study, we used the 1000 Genomes Project sequence data to explore the construction of PCs and their use in association analysis of LFVs or RVs for unrelated samples. It is shown that a few top PCs based on either CVs or LFVs could separate two continental groups, European and African samples, but those based on only RVs performed less well. When applied to several association tests in simulated data with population stratification, using PCs based on either CVs or LFVs was effective in controlling Type I error rates, while nonadjustment led to inflated Type I error rates. Perhaps the most interesting observation is that, although the PCs based on LFVs could better separate the two continental groups than those based on CVs, the use of the former could lead to overadjustment in the sense of substantial power loss in the absence of population stratification; in contrast, we did not see any problem with the use of the PCs based on CVs in all our examples.

  16. A Qualitative Analysis of Life Course Adjustment to Multiple Morbidity and Disability

    PubMed Central

    Harrison, Tracie; Taylor, Jessica; Fredland, Nina; Stuifbergen, Alexa; Walker, Janiece; Choban, Robin

    2012-01-01

    The accumulation of limitations over the life course requires that women re-adapt to environmental barriers that they encounter over time. The purpose of this qualitative case study is to detail the life experiences associated with living with mobility, cognitive, and sensory loss experienced by a woman and her sister who participated in an on-going ethnographic study of mobility impairment in women. In-depth interviews were subjected to thematic, life course analysis. A family case study was interpreted as an exemplar for aging with early onset disability into multiple morbidity, which was described as a series of loss, recovery and re-engagement. Within the case study, the participant suggested that because her functional limitations were not accommodated earlier in life due to societal and family level disadvantage, functional limitations were more difficult to adjust to in later years. PMID:23437442

  17. An automatic step adjustment method for average power analysis technique used in fiber amplifiers

    NASA Astrophysics Data System (ADS)

    Liu, Xue-Ming

    2006-04-01

    An automatic step adjustment (ASA) method for average power analysis (APA) technique used in fiber amplifiers is proposed in this paper for the first time. In comparison with the traditional APA technique, the proposed method has suggested two unique merits such as a higher order accuracy and an ASA mechanism, so that it can significantly shorten the computing time and improve the solution accuracy. A test example demonstrates that, by comparing to the APA technique, the proposed method increases the computing speed by more than a hundredfold under the same errors. By computing the model equations of erbium-doped fiber amplifiers, the numerical results show that our method can improve the solution accuracy by over two orders of magnitude at the same amplifying section number. The proposed method has the capacity to rapidly and effectively compute the model equations of fiber Raman amplifiers and semiconductor lasers.

  18. Analysis, design, and control of a novel optically commutated adjustable-speed motor

    NASA Astrophysics Data System (ADS)

    Newman, Wyatt S.; Risch, Ivan; Zhang, Yuandao; Garverick, Steven; Inerfield, Michael

    1998-12-01

    This paper describes the analysis, design and control of a novel, single-phase motor with a unique behavior resulting from the use of rotating power electronics mounted to the motor armature. Coils on the armature are selectively shorted by power MOSFET's which rotate with the armature, and torque is produced by interaction between currents induced in the shorted coils and the magnetic field produced by a stationary field coil. Control is limited to the timing of which armature coils are to be shorted as a function of armature speed and angle, it is possible to modulate torque production and obtain torque or speed control using only single-phase ac power and without the use of brushes or permanent magnets. An electro-mechanical model for this type of motor is presented and validated with respect to experimentation. The results show promise for achieving low- cost, adjustable-speed drives using this novel method of rotating electronics, optical communications, and computed commutation.

  19. Method of Individual Adjustment for 3D CT Analysis: Linear Measurement.

    PubMed

    Kim, Dong Kyu; Choi, Dong Hun; Lee, Jeong Woo; Yang, Jung Dug; Chung, Ho Yun; Cho, Byung Chae; Choi, Kang Young

    2016-01-01

    Introduction. We aim to regularize measurement values in three-dimensional (3D) computed tomography (CT) reconstructed images for higher-precision 3D analysis, focusing on length-based 3D cephalometric examinations. Methods. We measure the linear distances between points on different skull models using Vernier calipers (real values). We use 10 differently tilted CT scans for 3D CT reconstruction of the models and measure the same linear distances from the picture archiving and communication system (PACS). In both cases, each measurement is performed three times by three doctors, yielding nine measurements. The real values are compared with the PACS values. Each PACS measurement is revised based on the display field of view (DFOV) values and compared with the real values. Results. The real values and the PACS measurement changes according to tilt value have no significant correlations (p > 0.05). However, significant correlations appear between the real values and DFOV-adjusted PACS measurements (p < 0.001). Hence, we obtain a correlation expression that can yield real physical values from PACS measurements. The DFOV value intervals for various age groups are also verified. Conclusion. Precise confirmation of individual preoperative length and precise analysis of postoperative improvements through 3D analysis is possible, which is helpful for facial-bone-surgery symmetry correction.

  20. Method of Individual Adjustment for 3D CT Analysis: Linear Measurement

    PubMed Central

    Choi, Dong Hun; Lee, Jeong Woo; Yang, Jung Dug; Chung, Ho Yun; Cho, Byung Chae

    2016-01-01

    Introduction. We aim to regularize measurement values in three-dimensional (3D) computed tomography (CT) reconstructed images for higher-precision 3D analysis, focusing on length-based 3D cephalometric examinations. Methods. We measure the linear distances between points on different skull models using Vernier calipers (real values). We use 10 differently tilted CT scans for 3D CT reconstruction of the models and measure the same linear distances from the picture archiving and communication system (PACS). In both cases, each measurement is performed three times by three doctors, yielding nine measurements. The real values are compared with the PACS values. Each PACS measurement is revised based on the display field of view (DFOV) values and compared with the real values. Results. The real values and the PACS measurement changes according to tilt value have no significant correlations (p > 0.05). However, significant correlations appear between the real values and DFOV-adjusted PACS measurements (p < 0.001). Hence, we obtain a correlation expression that can yield real physical values from PACS measurements. The DFOV value intervals for various age groups are also verified. Conclusion. Precise confirmation of individual preoperative length and precise analysis of postoperative improvements through 3D analysis is possible, which is helpful for facial-bone-surgery symmetry correction. PMID:28070517

  1. Exercise as a treatment for depression: A meta-analysis adjusting for publication bias.

    PubMed

    Schuch, Felipe B; Vancampfort, Davy; Richards, Justin; Rosenbaum, Simon; Ward, Philip B; Stubbs, Brendon

    2016-06-01

    The effects of exercise on depression have been a source of contentious debate. Meta-analyses have demonstrated a range of effect sizes. Both inclusion criteria and heterogeneity may influence the effect sizes reported. The extent and influence of publication bias is also unknown. Randomized controlled trials (RCTs) were identified from a recent Cochrane review and searches of major electronic databases from 01/2013 to 08/2015. We included RCTs of exercise interventions in people with depression (including those with a diagnosis of major depressive disorder (MDD) or ratings on depressive symptoms), comparing exercise versus control conditions. A random effects meta-analysis calculating the standardized mean difference (SMD, 95% confidence interval; CI), meta-regressions, trim and fill and fail-safe n analyses were conducted. Twenty-five RCTs were included comparing exercise versus control comparison groups, including 9 examining participants with MDD. Overall, exercise had a large and significant effect on depression (SMD adjusted for publication bias = 1.11 (95% CI 0.79-1.43)) with a fail-safe number of 1057. Most adjusted analyses suggested publication bias led to an underestimated SMD. Larger effects were found for interventions in MDD, utilising aerobic exercise, at moderate and vigorous intensities, in a supervised and unsupervised format. In MDD, larger effects were found for moderate intensity, aerobic exercise, and interventions supervised by exercise professionals. Exercise has a large and significant antidepressant effect in people with depression (including MDD). Previous meta-analyses may have underestimated the benefits of exercise due to publication bias. Our data strongly support the claim that exercise is an evidence-based treatment for depression.

  2. INVESTIGATING DIFFERENCES IN BRAIN FUNCTIONAL NETWORKS USING HIERARCHICAL COVARIATE-ADJUSTED INDEPENDENT COMPONENT ANALYSIS

    PubMed Central

    Shi, Ran

    2016-01-01

    Human brains perform tasks via complex functional networks consisting of separated brain regions. A popular approach to characterize brain functional networks in fMRI studies is independent component analysis (ICA), which is a powerful method to reconstruct latent source signals from their linear mixtures. In many fMRI studies, an important goal is to investigate how brain functional networks change according to specific clinical and demographic variabilities. Existing ICA methods, however, cannot directly incorporate covariate effects in ICA decomposition. Heuristic post-ICA analysis to address this need can be inaccurate and inefficient. In this paper, we propose a hierarchical covariate-adjusted ICA (hc-ICA) model that provides a formal statistical framework for estimating covariate effects and testing differences between brain functional networks. Our method provides a more reliable and powerful statistical tool for evaluating group differences in brain functional networks while appropriately controlling for potential confounding factors. We present an analytically tractable EM algorithm to obtain maximum likelihood estimates of our model. We also develop a subspace-based approximate EM that runs significantly faster while retaining high accuracy. To test the differences in functional networks, we introduce a voxel-wise approximate inference procedure which eliminates the need of computationally expensive covariance matrix estimation and inversion. We demonstrate the advantages of our methods over the existing method via simulation studies. We apply our method to an fMRI study to investigate differences in brain functional networks associated with post-traumatic stress disorder (PTSD).

  3. Mathematical Analysis of Biomolecular Network Reveals Connections Between Diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2012-02-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions.

  4. Parental Attachment, Separation-Individuation, and College Student Adjustment: A Structural Equation Analysis of Mediational Effects

    ERIC Educational Resources Information Center

    Mattanah, Jonathan F.; Hancock, Gregory R.; Brand, Bethany L.

    2004-01-01

    Secure parental attachment and healthy levels of separation-individuation have been consistently linked to greater college student adjustment. The present study proposes that the relation between parental attachment and college adjustment is mediated by healthy separation-individuation. The authors gathered data on maternal and paternal…

  5. A Multivariate Analysis of Emotional and Behavioral Adjustment and Preschool Educational Outcomes

    ERIC Educational Resources Information Center

    Fantuzzo, John; Bulotsky, Rebecca; McDermott, Paul; Mosca, Samuel; Lutz, Megan Noone

    2003-01-01

    The study examined the multivariate relationship between dimensions of preschool emotional and behavioral adjustment assessed at the beginning of the year by the Adjustment Scales for Preschool Intervention (ASPI) and multiple learning and social competencies at the end of the year with an urban Head Start sample. This study also examined the…

  6. Children's exposure to intimate partner violence: A meta-analysis of longitudinal associations with child adjustment problems.

    PubMed

    Vu, Nicole L; Jouriles, Ernest N; McDonald, Renee; Rosenfield, David

    2016-06-01

    This meta-analysis reviewed 74 studies that examined longitudinal associations between children's exposure to intimate partner violence (IPV) and their adjustment problems. Results indicated that children's exposure to IPV is linked prospectively with child externalizing, internalizing, and total adjustment problems. Moreover, the magnitude of the association between IPV exposure and child externalizing and internalizing problems strengthens over time. In addition, associations are stronger between IPV exposure and child externalizing and internalizing problems when IPV is conceptualized broadly rather than narrowly (physical IPV+psychological and/or sexual IPV versus physical IPV only), and when information on IPV and child adjustment problems is obtained from the same source, rather than independent sources. When IPV exposure is measured at younger ages, compared to older ages, the association between IPV and child externalizing problems is greater. However, when child adjustment problems are measured at older ages, compared to younger ages, the association between IPV and child internalizing problems is greater. Child sex, sample type, and whether only the male partner's violence or both partners' violence was measured did not predict the association between children's exposure to IPV and later adjustment problems. The findings have both research and clinical implications regarding the long-term adjustment of children exposed to IPV and the conceptualization and measurement of resilience subsequent to IPV.

  7. Blinded sample size recalculation for clinical trials with normal data and baseline adjusted analysis.

    PubMed

    Friede, Tim; Kieser, Meinhard

    2011-01-01

    Baseline adjusted analyses are commonly encountered in practice, and regulatory guidelines endorse this practice. Sample size calculations for this kind of analyses require knowledge of the magnitude of nuisance parameters that are usually not given when the results of clinical trials are reported in the literature. It is therefore quite natural to start with a preliminary calculated sample size based on the sparse information available in the planning phase and to re-estimate the value of the nuisance parameters (and with it the sample size) when a portion of the planned number of patients have completed the study. We investigate the characteristics of this internal pilot study design when an analysis of covariance with normally distributed outcome and one random covariate is applied. For this purpose we first assess the accuracy of four approximate sample size formulae within the fixed sample size design. Then the performance of the recalculation procedure with respect to its actual Type I error rate and power characteristics is examined. The results of simulation studies show that this approach has favorable properties with respect to the Type I error rate and power. Together with its simplicity, these features should make it attractive for practical application.

  8. Refinement of Stereo Image Analysis Using Photometric Shape Recovery as AN Alternative to Bundle Adjustment

    NASA Astrophysics Data System (ADS)

    Grumpe, A.; Schröer, C.; Kauffmann, S.; Fricke, T.; Wöhler, C.; Mall, U.

    2016-06-01

    Topographic mapping, e.g. the generation of Digital Elevation Models (DEM), is of general interest to the remote sensing community and scientific research. Commonly, photogrammetric methods, e.g. stereo image analysis methods (SIAM) or bundle adjustment methods (BAM), are applied to derive 3D information based on multiple images of an area. These methods require the detection of control points, i.e. common points within multiple images, which relies on a similarity measure and usually yields a sparse map of 3D points. The full spatial DEM is then obtained by interpolation techniques or imposed restrictions, e.g. smoothness constraints. Since BAM utilizes all images of the area, it is assumed to provide a more accurate DEM than SIAM which utilizes only pairs of images. Intensity-based shape recovery, e.g. shape from shading (SfS), utilizes the reflectance behavior of the object surface and thus provides a dense map of relative height changes, which provide the possibility to refine the photogrammetric DEMs. Based on Rosetta NavCam images of 67P/Churyumov-Gerasimenko we compare intensity-based DEM refinement methods which use DEMs obtained based on SIAM and BAM as a reference. We show that both the SIAM based DEM refinement and the BAM based DEM refinement are of similar quality. It is thus possible to derive DEMs of high lateral resolution by applying the intensity-based refinement to the less complex SIAM.

  9. Genomic analysis of primordial dwarfism reveals novel disease genes.

    PubMed

    Shaheen, Ranad; Faqeih, Eissa; Ansari, Shinu; Abdel-Salam, Ghada; Al-Hassnan, Zuhair N; Al-Shidi, Tarfa; Alomar, Rana; Sogaty, Sameera; Alkuraya, Fowzan S

    2014-02-01

    Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

  10. Farm Business Management Analysis: Adjusting the Farm Business to Increase Profit. Unit III. Volume 15, Number 3. Instructor's Guide.

    ERIC Educational Resources Information Center

    Denker, Robert; And Others

    Designed primarily for Missouri vocational agricultural instructors participating in the Farm Business Management Analysis Program, this instructor's guide, consisting of 10 lessons, deals with adjusting a farm business to increase profits. The following topics are covered in the individual lessons: law and the farm family, planning income tax…

  11. A Meta-Analysis of the Effects of Cross-Cultural Training on Expatriate Performance and Adjustment.

    ERIC Educational Resources Information Center

    Morris, Mark A.; Robie, Chet

    2001-01-01

    Meta-analysis of 16 studies of expatriate managers' adjustment and 25 of expatriate job performance showed that mean effect sizes were lower than in previous analyses. Cautions about basing cross-cultural training on results of such studies were expressed. (Contains 68 references.) (SK)

  12. The Games Analysis Intervention: A Procedure to Increase the Peer Acceptance and Social Adjustment of Socially Isolated Children.

    ERIC Educational Resources Information Center

    Marlowe, Mike

    The effectiveness of a therapeutic motor development program in increasing the social adjustment and peer acceptance of seven socially isolated fifth grade children was investigated using a single subject experimental design. The program was based on the games analysis model which allows movement games to be designed for individual motoric,…

  13. Comparative analysis reveals the underlying mechanism of vertebrate seasonal reproduction.

    PubMed

    Ikegami, Keisuke; Yoshimura, Takashi

    2016-02-01

    Animals utilize photoperiodic changes as a calendar to regulate seasonal reproduction. Birds have highly sophisticated photoperiodic mechanisms and functional genomics analysis in quail uncovered the signal transduction pathway regulating avian seasonal reproduction. Birds detect light with deep brain photoreceptors. Long day (LD) stimulus induces secretion of thyroid-stimulating hormone (TSH) from the pars tuberalis (PT) of the pituitary gland. PT-derived TSH locally activates thyroid hormone (TH) in the hypothalamus, which induces gonadotropin-releasing hormone (GnRH) and hence gonadotropin secretion. However, during winter, low temperatures increase serum TH for adaptive thermogenesis, which accelerates germ cell apoptosis by activating the genes involved in metamorphosis. Therefore, TH has a dual role in the regulation of seasonal reproduction. Studies using TSH receptor knockout mice confirmed the involvement of PT-derived TSH in mammalian seasonal reproduction. In addition, studies in mice revealed that the tissue-specific glycosylation of TSH diversifies its function in the circulation to avoid crosstalk. In contrast to birds and mammals, one of the molecular machineries necessary for the seasonal reproduction of fish are localized in the saccus vasculosus from the photoreceptor to the neuroendocrine output. Thus, comparative analysis is a powerful tool to uncover the universality and diversity of fundamental properties in various organisms.

  14. The African Development Bank, structural adjustment, and child mortality: a cross-national analysis of Sub-Saharan Africa.

    PubMed

    Pandolfelli, Lauren E; Shandra, John M

    2013-01-01

    We conduct a cross-national analysis to test the hypothesis that African Development Bank (AfDB) structural adjustment adversely impacts child mortality in Sub-Saharan Africa. We use generalized least square random effects regression models and two-step Heckman models that correct for selection bias using data on 35 nations with up to four time points (1990, 1995, 2000, and 2005). We find substantial support for our hypothesis, which indicates that Sub-Saharan African nations that receive an AfDB structural adjustment loan tend to have higher levels of child mortality than Sub-Saharan African nations that do not receive such a loan. This finding remains stable even when controlling for selection bias on whether or not a Sub-Saharan African nation receives an AfDB structural adjustment loan. We conclude by discussing the methodological implications of the article, policy suggestions, and possible directions for future research.

  15. Nonparametric randomization-based covariate adjustment for stratified analysis of time-to-event or dichotomous outcomes.

    PubMed

    Hussey, Michael A; Koch, Gary G; Preisser, John S; Saville, Benjamin R

    2016-01-01

    Time-to-event or dichotomous outcomes in randomized clinical trials often have analyses using the Cox proportional hazards model or conditional logistic regression, respectively, to obtain covariate-adjusted log hazard (or odds) ratios. Nonparametric Randomization-Based Analysis of Covariance (NPANCOVA) can be applied to unadjusted log hazard (or odds) ratios estimated from a model containing treatment as the only explanatory variable. These adjusted estimates are stratified population-averaged treatment effects and only require a valid randomization to the two treatment groups and avoid key modeling assumptions (e.g., proportional hazards in the case of a Cox model) for the adjustment variables. The methodology has application in the regulatory environment where such assumptions cannot be verified a priori. Application of the methodology is illustrated through three examples on real data from two randomized trials.

  16. Analysis of error-prone survival data under additive hazards models: measurement error effects and adjustments.

    PubMed

    Yan, Ying; Yi, Grace Y

    2016-07-01

    Covariate measurement error occurs commonly in survival analysis. Under the proportional hazards model, measurement error effects have been well studied, and various inference methods have been developed to correct for error effects under such a model. In contrast, error-contaminated survival data under the additive hazards model have received relatively less attention. In this paper, we investigate this problem by exploring measurement error effects on parameter estimation and the change of the hazard function. New insights of measurement error effects are revealed, as opposed to well-documented results for the Cox proportional hazards model. We propose a class of bias correction estimators that embraces certain existing estimators as special cases. In addition, we exploit the regression calibration method to reduce measurement error effects. Theoretical results for the developed methods are established, and numerical assessments are conducted to illustrate the finite sample performance of our methods.

  17. Molecular-Genetic Analysis of Osmoregulation, Osmotic Adjustment and Growth in Arabidopsis

    SciTech Connect

    Elizabeth Bray

    2009-05-04

    The molecular mechanism by which plants control cellular solute and water content, called osmoregulation, is critical for cell expansion and survival, particularly in response to cellular water deficit or low water potential. Two loci, lwr1 and lwr2 (low water potential response), that affect osmoregulation were isolated as part of a larger screen to identify mutants with alterations in low water potential-induced proline accumulation. When seedlings of lwr2 were exposed to a steady low water potential stress over a period of several days using PEG-infused agar plates, the mutants had lesser proline accumulation and osmotic adjustment than the wild type, Ben. A mapping population was raised but it was not possible to reliably identify the mutants in the population and thus could not be used for mapping. The mutant lwr1 was mapped and the gene identified. The mutant lwr1 had greater accumulation of proline, higher total solute content, greater osmotic adjustment at low water potential, altered abscisic acid content, and increased sensitivity to applied abscisic acid with respect to Pro content than the wild type, Ben, when the water potential was decreased over a period of several days using PEG-infused agar plates. lwr1 also had altered growth and morphology, including defects in trichome branching with the majority of the trichomes having a single point, shortened siliques which were crooked, and significantly lengthened time to flowering. Using bulk segregant analysis, the lwr1 loci was mapped to the lower arm of chromosome II, near the marker nga168. Further detailed fine mapping located the mutation to the gene PKL, At2g25170, which was previously identified as a gene involved in altered root development. PKL encodes a chromatin remodeling factor. The mutation in lwr1 introduced a stop codon in the 14th exon of At2g25170. The mutant was not complemented by 4 other known mutants having a disrupted PKL gene confirming the placement of this mutation in lwr1. In

  18. Phosphoproteomic Analysis Reveals Regulatory Mechanisms at the Kidney Filtration Barrier

    PubMed Central

    Rinschen, Markus M.; Wu, Xiongwu; König, Tim; Pisitkun, Trairak; Hagmann, Henning; Pahmeyer, Caroline; Lamkemeyer, Tobias; Kohli, Priyanka; Schnell, Nicole; Schermer, Bernhard; Dryer, Stuart; Brooks, Bernard R.; Beltrao, Pedro; Krueger, Marcus

    2014-01-01

    Diseases of the kidney filtration barrier are a leading cause of ESRD. Most disorders affect the podocytes, polarized cells with a limited capacity for self-renewal that require tightly controlled signaling to maintain their integrity, viability, and function. Here, we provide an atlas of in vivo phosphorylated, glomerulus-expressed proteins, including podocyte-specific gene products, identified in an unbiased tandem mass spectrometry–based approach. We discovered 2449 phosphorylated proteins corresponding to 4079 identified high-confidence phosphorylated residues and performed a systematic bioinformatics analysis of this dataset. We discovered 146 phosphorylation sites on proteins abundantly expressed in podocytes. The prohibitin homology domain of the slit diaphragm protein podocin contained one such site, threonine 234 (T234), located within a phosphorylation motif that is mutated in human genetic forms of proteinuria. The T234 site resides at the interface of podocin dimers. Free energy calculation through molecular dynamic simulations revealed a role for T234 in regulating podocin dimerization. We show that phosphorylation critically regulates formation of high molecular weight complexes and that this may represent a general principle for the assembly of proteins containing prohibitin homology domains. PMID:24511133

  19. Geosat crossover analysis in the tropical Pacific. Part 1: Constrained sinusoidal crossover adjustment

    NASA Technical Reports Server (NTRS)

    Tai, Chang-Kou

    1988-01-01

    A new method (constrained sinusoidal crossover adjustment) for removing the orbit error in satellite altimetry is tested (using crossovers accumulated in the first 91 days of the Geosat non-repeat era in the tropical Pacific) and found to have excellent qualities. Two features distinguish the new method from the conventional bias-and-tilt crossover adjustment. First, a sine wave (with wavelength equaling the circumference of the Earth) is used to represent the orbit error for each satellite revolution, instead of the bias-and-tilt (and curvature, if necessary) approach for each segment of the satellite ground track. Secondly, the indeterminacy of the adjustment process is removed by a simple constraint minimizing the amplitudes of the sine waves, rather than by fixing selected tracks. Overall the new method is more accurate, more efficient, and much less cumbersome than the old. The idea of restricting the crossover adjustment to crossovers between tracks that are less than certain days apart in order to preserve the large-scale long-term oceanic variability is also tested with inconclusive results because the orbit error was unusually nonstationary in the initial 91 days of the GEOSAT mission.

  20. The Effects of the Family Foundations Prevention Program on Coparenting and Child Adjustment: A Mediation Analysis

    PubMed Central

    Solmeyer, Anna R.; Feinberg, Mark E.; Coffman, Donna L.; Jones, Damon E.

    2013-01-01

    Behavioral and emotional problems are common in early childhood and put children at risk for developing more serious problems. This study tested the mediating mechanisms through which a universal coparenting intervention implemented during the transition to parenthood led to reduced child adjustment problems at age 3, and explored child gender as a potential moderator. 169 heterosexual couples expecting their first child were randomly assigned to a control condition or Family Foundations, a series of eight classes that targeted the coparenting relationship. Data were collected through videotaped triadic mother-father-child interaction tasks when the child was 1 and 3 years of age. Separate longitudinal path analyses for mothers and fathers tested coparenting competition and positivity as mediators of program effects on child adjustment problems. Significant mediated effects for coparenting competition were found for fathers with both sons and daughters and for mothers with sons, but not for mothers with daughters. These effects accounted for between 39 and 55% of the intervention’s impact on child adjustment problems. Coparenting positivity did not mediate program effects. These results support the use of a prevention approach to reduce coparenting competition and enhance child adjustment, and provide information that can be used to refine theory. PMID:23404669

  1. Marital Adjustment in Parents of Children with Disabilities: A Historical Review and Meta- Analysis

    ERIC Educational Resources Information Center

    Risdal, Don; Singer, George H. S.

    2004-01-01

    This report uses meta-analytic methods to reexamine a body of research literature on comparative levels of divorce and marital satisfaction/discord in parents of children with and without developmental disabilities in light of new assumptions about variability in family adjustment, including successful family adaptation and longterm resilience. A…

  2. Factors Associated with Community Adjustment of Young Adults with Serious Emotional Disturbance: A Longitudinal Analysis.

    ERIC Educational Resources Information Center

    Armstrong, Kathleen H.; Dedrick, Robert F.; Greenbaum, Paul E.

    2003-01-01

    Rates of change in behaviors in relation to community adjustment were examined for 292 participants in the 7-year longitudinal National Adolescent and Child Treatment Study (NACTS) as they transitioned to the adult world. Participants with initially higher social-adaptive behavior and whose behavior improved over time attained higher adjustment…

  3. Children's Sleep and Adjustment: A Residualized Change Analysis

    ERIC Educational Resources Information Center

    El-Sheikh, Mona; Bub, Kristen L.; Kelly, Ryan J.; Buckhalt, Joseph A.

    2013-01-01

    We investigated longitudinal relations between children's sleep and symptoms of depression, anxiety, and anger/aggression. We expected that initial sleep problems and increases in these problems over time would be associated with worse adjustment outcomes. The study had 3 waves with 1-year lags. At Time 1 [T1], 128 girls and 123 boys (M age =…

  4. The Predictive Analysis of Adjustment Difficulties from Loneliness, Social Support, and Social Connectedness

    ERIC Educational Resources Information Center

    Duru, Erdinc

    2008-01-01

    The purpose of the study was to examine direct and indirect effects of social support, social connectedness, and loneliness in predicting adjustment difficulties. The sample of the study was 404 university students (212 females and 192 males) studying in different departments of the Faculty of Education at Pamukkale University. The ages of the…

  5. Examining the Cultural Adjustment Experiences of African International College Students: A Qualitative Analysis

    ERIC Educational Resources Information Center

    Constantine, Madonna G.; Anderson, Gregory M.; Berkel, LaVerne A.; Caldwell, Leon D.; Utsey, Shawn O.

    2005-01-01

    The authors examined the cultural adjustment experiences of 12 Kenyan, Nigerian, and Ghanaian international college students through semistructured interviews. Using consensual qualitative research methodology (C. E. Hill, B. J. Thompson, & E. N. Williams, 1997), 7 primary domains or themes related to these students' cultural adjustment…

  6. Distributive Education and Occupational Work Adjustment. Topic Analysis for Vocational Teacher Education.

    ERIC Educational Resources Information Center

    Ohio State Dept. of Education, Columbus. Div. of Vocational Education.

    Six papers on distributive education and occupational work adjustment (OWA) which were presented at a teacher education leadership conference on the development of common core curriculum for vocational education teachers are contained in this booklet. The title and authors are as follow: "Methods of Teaching Distributive Education," by John…

  7. Community Involvement and Victimization at School: An Analysis through Family, Personal and Social Adjustment

    ERIC Educational Resources Information Center

    Jimenez, Teresa Isabel; Musitu, Gonzalo; Ramos, Manuel Jesus; Murgui, Sergio

    2009-01-01

    The present study analyzes the impact of adolescents' community involvement on victimization by peers at school through various indicators of family, personal and social adjustment (openness of communication with mother and father, life satisfaction, social self-esteem, and loneliness). Participating in the project were 565 adolescents aged 11 to…

  8. Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

    PubMed Central

    Huang, Lam O.; Infante-Rivard, Claire; Labbe, Aurélie

    2016-01-01

    Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies. PMID:27630667

  9. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison.

    PubMed

    Forgacs, David; Wallen, Rick L; Dobson, Lauren K; Derr, James N

    2016-01-01

    Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06). Spatial analysis of these mitochondrial DNA (mtDNA) haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76). However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites) from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison) and Canadian wood bison (B. b. athabascae). Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions.

  10. Mitochondrial Genome Analysis Reveals Historical Lineages in Yellowstone Bison

    PubMed Central

    Derr, James N.

    2016-01-01

    Yellowstone National Park is home to one of the only plains bison populations that have continuously existed on their present landscape since prehistoric times without evidence of domestic cattle introgression. Previous studies characterized the relatively high levels of nuclear genetic diversity in these bison, but little is known about their mitochondrial haplotype diversity. This study assessed mitochondrial genomes from 25 randomly selected Yellowstone bison and found 10 different mitochondrial haplotypes with a haplotype diversity of 0.78 (± 0.06). Spatial analysis of these mitochondrial DNA (mtDNA) haplotypes did not detect geographic population subdivision (FST = -0.06, p = 0.76). However, we identified two independent and historically important lineages in Yellowstone bison by combining data from 65 bison (defined by 120 polymorphic sites) from across North America representing a total of 30 different mitochondrial DNA haplotypes. Mitochondrial DNA haplotypes from one of the Yellowstone lineages represent descendants of the 22 indigenous bison remaining in central Yellowstone in 1902. The other mitochondrial DNA lineage represents descendants of the 18 females introduced from northern Montana in 1902 to supplement the indigenous bison population and develop a new breeding herd in the northern region of the park. Comparing modern and historical mitochondrial DNA diversity in Yellowstone bison helps uncover a historical context of park restoration efforts during the early 1900s, provides evidence against a hypothesized mitochondrial disease in bison, and reveals the signature of recent hybridization between American plains bison (Bison bison bison) and Canadian wood bison (B. b. athabascae). Our study demonstrates how mitochondrial DNA can be applied to delineate the history of wildlife species and inform future conservation actions. PMID:27880780

  11. Quantitative flux analysis reveals folate-dependent NADPH production

    NASA Astrophysics Data System (ADS)

    Fan, Jing; Ye, Jiangbin; Kamphorst, Jurre J.; Shlomi, Tomer; Thompson, Craig B.; Rabinowitz, Joshua D.

    2014-06-01

    ATP is the dominant energy source in animals for mechanical and electrical work (for example, muscle contraction or neuronal firing). For chemical work, there is an equally important role for NADPH, which powers redox defence and reductive biosynthesis. The most direct route to produce NADPH from glucose is the oxidative pentose phosphate pathway, with malic enzyme sometimes also important. Although the relative contribution of glycolysis and oxidative phosphorylation to ATP production has been extensively analysed, similar analysis of NADPH metabolism has been lacking. Here we demonstrate the ability to directly track, by liquid chromatography-mass spectrometry, the passage of deuterium from labelled substrates into NADPH, and combine this approach with carbon labelling and mathematical modelling to measure NADPH fluxes. In proliferating cells, the largest contributor to cytosolic NADPH is the oxidative pentose phosphate pathway. Surprisingly, a nearly comparable contribution comes from serine-driven one-carbon metabolism, in which oxidation of methylene tetrahydrofolate to 10-formyl-tetrahydrofolate is coupled to reduction of NADP+ to NADPH. Moreover, tracing of mitochondrial one-carbon metabolism revealed complete oxidation of 10-formyl-tetrahydrofolate to make NADPH. As folate metabolism has not previously been considered an NADPH producer, confirmation of its functional significance was undertaken through knockdown of methylenetetrahydrofolate dehydrogenase (MTHFD) genes. Depletion of either the cytosolic or mitochondrial MTHFD isozyme resulted in decreased cellular NADPH/NADP+ and reduced/oxidized glutathione ratios (GSH/GSSG) and increased cell sensitivity to oxidative stress. Thus, although the importance of folate metabolism for proliferating cells has been long recognized and attributed to its function of producing one-carbon units for nucleic acid synthesis, another crucial function of this pathway is generating reducing power.

  12. Postural adjustments associated with rapid voluntary arm movements. II. Biomechanical analysis.

    PubMed Central

    Friedli, W G; Cohen, L; Hallett, M; Stanhope, S; Simon, S R

    1988-01-01

    Normal subjects performed bilaterally symmetric rapid elbow flexions or extensions ("focal movements") while standing. Specific patterns of electromyographic activity in leg and trunk muscles ("associated postural adjustments") were seen for each type of movement. The biomechanical significance of these postural adjustments was analysed by means of the ground reaction forces and motion of the various body segments. Experimental data were compared with that from a theoretical model of the body consisting of a six segment kinetic chain with rigid links. Distinct patterns of the ground reaction forces with elbow flexion were opposite in direction to those seen with elbow extension. Movements of the various body segments were small and specific for a certain focal movement. Dynamic perturbations arising from the arm movement in an anteroposterior direction were found to be compensated by postural adjustments, whereas vertical perturbations were not compensated. The muscular activity acting about different joints in the different movements was found to correlate with the predictions of activity needed to compensate for net joint reaction moments arising from the focal movement. Motion of the various body segments could be understood as resulting from the interplay of the net reaction moments and the net muscular moments at the different joints. Dynamic postural requirements are accomplished by a precise active compensation initiated before the focal movement. PMID:3346688

  13. Return period adjustment for runoff coefficients based on analysis in undeveloped Texas watersheds

    USGS Publications Warehouse

    Dhakal, Nirajan; Fang, Xing; Asquith, William H.; Cleveland, Theodore G.; Thompson, David B.

    2013-01-01

    The rational method for peak discharge (Qp) estimation was introduced in the 1880s. The runoff coefficient (C) is a key parameter for the rational method that has an implicit meaning of rate proportionality, and the C has been declared a function of the annual return period by various researchers. Rate-based runoff coefficients as a function of the return period, C(T), were determined for 36 undeveloped watersheds in Texas using peak discharge frequency from previously published regional regression equations and rainfall intensity frequency for return periods T of 2, 5, 10, 25, 50, and 100 years. The C(T) values and return period adjustments C(T)/C(T=10  year) determined in this study are most applicable to undeveloped watersheds. The return period adjustments determined for the Texas watersheds in this study and those extracted from prior studies of non-Texas data exceed values from well-known literature such as design manuals and textbooks. Most importantly, the return period adjustments exceed values currently recognized in Texas Department of Transportation design guidance when T>10  years.

  14. The role of anticipatory postural adjustments in compensatory control of posture: 2. Biomechanical analysis.

    PubMed

    Santos, Marcio J; Kanekar, Neeta; Aruin, Alexander S

    2010-06-01

    The central nervous system (CNS) utilizes anticipatory (APAs) and compensatory (CPAs) postural adjustments to maintain equilibrium while standing. It is known that these postural adjustments involve displacements of the center of mass (COM) and center of pressure (COP). The purpose of the study was to investigate the relationship between APAs and CPAs from a kinetic and kinematic perspective. Eight subjects were exposed to external predictable and unpredictable perturbations induced at the shoulder level while standing. Kinematic and kinetic data were recorded and analyzed during the time duration typical for anticipatory and compensatory postural adjustments. When the perturbations were unpredictable, the COM and COP displacements were larger compared to predictable conditions with APAs. Thus, the peak of COM displacement, after the pendulum impact, in the posterior direction reached 28+/-9.6mm in the unpredictable conditions with no APAs whereas it was 1.6 times smaller, reaching 17+/-5.5mm during predictable perturbations. Similarly, after the impact, the peak of COP displacement in the posterior direction was 60+/-14 mm for unpredictable conditions and 28+/-3.6mm for predictable conditions. Finally, the times of the peak COM and COP displacements were similar in the predictable and unpredictable conditions. This outcome provides additional knowledge about how body balance is controlled in presence and in absence of information about the forthcoming perturbation. Moreover, it suggests that control of posture could be enhanced by better utilization of APAs and such an approach could be considered as a valuable modality in the rehabilitation of individuals with balance impairment.

  15. Chiropractic Adjustment

    MedlinePlus

    ... structural alignment and improve your body's physical function. Low back pain, neck pain and headache are the most common ... treated. Chiropractic adjustment can be effective in treating low back pain, although much of the research done shows only ...

  16. Adjustment disorder

    MedlinePlus

    ... from other people Skipped heartbeats and other physical complaints Trembling or twitching To have adjustment disorder, you ... ADAM Health Solutions. About MedlinePlus Site Map FAQs Customer Support Get email updates Subscribe to RSS Follow ...

  17. The role of anticipatory postural adjustments in compensatory control of posture: 1. Electromyographic analysis.

    PubMed

    Santos, Marcio J; Kanekar, Neeta; Aruin, Alexander S

    2010-06-01

    Anticipatory (APAs) and compensatory (CPAs) postural adjustments are the two principal mechanisms that the central nervous system uses to maintain equilibrium while standing. We studied the role of APAs in compensatory postural adjustments. Eight subjects were exposed to external predictable and unpredictable perturbations induced at the shoulder level, while standing with eyes open and closed. Electrical activity of leg and trunk muscles was recorded and analyzed during four epochs representing the time duration typical for anticipatory and compensatory postural control. No anticipatory activity of the trunk and leg muscles was seen in the case of unpredictable perturbations; instead, significant compensatory activation of muscles was observed. When the perturbations were predictable, strong anticipatory activation was seen in all the muscles: such APAs were associated with significantly smaller compensatory activity of muscles and COP displacements after the perturbations. The outcome of the study highlights the importance of APAs in control of posture and points out the existence of a relationship between the anticipatory and the compensatory components of postural control. It also suggests a possibility to enhance balance control by improving the APAs responses during external perturbations.

  18. Analysis of cancer genomes reveals basic features of human aging and its role in cancer development

    PubMed Central

    Podolskiy, Dmitriy I.; Lobanov, Alexei V.; Kryukov, Gregory V.; Gladyshev, Vadim N.

    2016-01-01

    Somatic mutations have long been implicated in aging and disease, but their impact on fitness and function is difficult to assess. Here by analysing human cancer genomes we identify mutational patterns associated with aging. Our analyses suggest that age-associated mutation load and burden double approximately every 8 years, similar to the all-cause mortality doubling time. This analysis further reveals variance in the rate of aging among different human tissues, for example, slightly accelerated aging of the reproductive system. Age-adjusted mutation load and burden correlate with the corresponding cancer incidence and precede it on average by 15 years, pointing to pre-clinical cancer development times. Behaviour of mutation load also exhibits gender differences and late-life reversals, explaining some gender-specific and late-life patterns in cancer incidence rates. Overall, this study characterizes some features of human aging and offers a mechanism for age being a risk factor for the onset of cancer. PMID:27515585

  19. Introducing conjoint analysis method into delayed lotteries studies: its validity and time stability are higher than in adjusting

    PubMed Central

    Białek, Michał; Markiewicz, Łukasz; Sawicki, Przemysław

    2015-01-01

    The delayed lotteries are much more common in everyday life than are pure lotteries. Usually, we need to wait to find out the outcome of the risky decision (e.g., investing in a stock market, engaging in a relationship). However, most research has studied the time discounting and probability discounting in isolation using the methodologies designed specifically to track changes in one parameter. Most commonly used method is adjusting, but its reported validity and time stability in research on discounting are suboptimal. The goal of this study was to introduce the novel method for analyzing delayed lotteries—conjoint analysis—which hypothetically is more suitable for analyzing individual preferences in this area. A set of two studies compared the conjoint analysis with adjusting. The results suggest that individual parameters of discounting strength estimated with conjoint have higher predictive value (Study 1 and 2), and they are more stable over time (Study 2) compared to adjusting. We discuss these findings, despite the exploratory character of reported studies, by suggesting that future research on delayed lotteries should be cross-validated using both methods. PMID:25674069

  20. Mass transport analysis: inhalation rfc methods framework for interspecies dosimetric adjustment.

    PubMed

    Hanna, L M; Lou, S R; Su, S; Jarabek, A M

    2001-05-01

    In 1994, the U.S. Environmental Protection Agency introduced dosimetry modeling into the methods used to derive an inhalation reference concentration (RfC). The type of dosimetric adjustment factor (DAF) applied had to span the range of physicochemical characteristics of the gases listed on the Clean Air Act Amendments in 1991 as hazardous air pollutants (HAPs) and accommodate differences in available data with respect to their toxicokinetic properties. A framework was proposed that allowed for a hierarchy of dosimetry model structures, from optimal to rudimentary, and a category scheme that provided for limiting model structures based on physicochemical and toxicokinetic properties. These limiting cases were developed from restricting consideration to specific properties relying on an understanding of the generalized system based on mass transport theory. Physiochemical characteristics included the solubility and reactivity (e.g., propensity to dissociate, oxidize, or serve as a metabolic substrate) of the gas and were used as major determinants of absorption. Dosimetric adjustments were developed to evaluate portal of entry (POE) effects as well as remote (systemic) effects relevant to the toxicokinetic properties of the gas of interest. The gas categorization scheme consisted of defining three gas categories: (1) gases that are highly soluble and/or reactive, absorbing primarily in the extrathoracic airways; (2) gases that are moderately soluble and/or reactive, absorbing throughout the airways, as well as accumulating in the bloodstream; and (3) gases that have a low water solubility and are lipid soluble such that they are primarily absorbed in the pulmonary region and likely to act systemically. This article presents the framework and the mass transport theory behind the RfC method. Comparison to compartmental approaches and considerations for future development are also discussed.

  1. Directional Variance Adjustment: Bias Reduction in Covariance Matrices Based on Factor Analysis with an Application to Portfolio Optimization

    PubMed Central

    Bartz, Daniel; Hatrick, Kerr; Hesse, Christian W.; Müller, Klaus-Robert; Lemm, Steven

    2013-01-01

    Robust and reliable covariance estimates play a decisive role in financial and many other applications. An important class of estimators is based on factor models. Here, we show by extensive Monte Carlo simulations that covariance matrices derived from the statistical Factor Analysis model exhibit a systematic error, which is similar to the well-known systematic error of the spectrum of the sample covariance matrix. Moreover, we introduce the Directional Variance Adjustment (DVA) algorithm, which diminishes the systematic error. In a thorough empirical study for the US, European, and Hong Kong stock market we show that our proposed method leads to improved portfolio allocation. PMID:23844016

  2. Meta-analysis of lung cancer in asphalt roofing and paving workers with external adjustment for confounding by coal tar

    SciTech Connect

    Fayerweather, W.E.

    2007-07-01

    The study's objectives were to update Partanen's and Boffetta's 1994 meta-analysis of lung cancer among roofing and paving asphalt workers and explore the role of coal tar in explaining the statistical heterogeneity among these studies. Information retrieval strategies and eligibility criteria were defined for identifying the epidemiologic studies to be included in the analysis. The relative risk ratio (RR) for lung cancer was selected as the effect measure of interest. Coal tar bias factors were developed and used to externally adjust each eligible study's published RR for confounding by coal tar. The meta-Relative Risk (meta-RR) and its variance were estimated by general variance-based methods. Heterogeneity of the RRs was assessed by heterogeneity chi-square and I{sup 2} tests. The results from this update were similar to those in Partanen's and Boffetta's original meta-analysis. Although the meta-RRs for the roofers and the pavers were no longer statistically significantly different from one another, significant heterogeneity remained within each of the coal tar-adjusted sectors. Meta-analysis of non-experimental epidemiologic studies is subject to significant uncertainties as is externally correcting studies for confounding. Given these uncertainties, the specific quantitative estimates in this (or any similar) analysis must be viewed with caution. Nevertheless, this analysis provides support for the hypothesis proposed by several major reviewers that confounding by coal tar-related PAH exposures may explain most or all of the lung cancer risks found in the epidemiologic literature on asphalt roofing and paving workers.

  3. Subfield profitability analysis reveals an economic case for cropland diversification

    NASA Astrophysics Data System (ADS)

    Brandes, E.; McNunn, G. S.; Schulte, L. A.; Bonner, I. J.; Muth, D. J.; Babcock, B. A.; Sharma, B.; Heaton, E. A.

    2016-01-01

    Public agencies and private enterprises increasingly desire to achieve ecosystem service outcomes in agricultural systems, but are limited by perceived conflicts between economic and ecosystem service goals and a lack of tools enabling effective operational management. Here we use Iowa—an agriculturally homogeneous state representative of the Maize Belt—to demonstrate an economic rationale for cropland diversification at the subfield scale. We used a novel computational framework that integrates disparate but publicly available data to map ˜3.3 million unique potential management polygons (9.3 Mha) and reveal subfield opportunities to increase overall field profitability. We analyzed subfield profitability for maize/soybean fields during 2010-2013—four of the most profitable years in recent history—and projected results for 2015. While cropland operating at a loss of US 250 ha-1 or more was negligible between 2010 and 2013 at 18 000-190 000 ha (<2% of row-crop land), the extent of highly unprofitable land increased to 2.5 Mha, or 27% of row-crop land, in the 2015 projection. Aggregation of these areas to the township level revealed ‘hotspots’ for potential management change in Western, Central, and Northeast Iowa. In these least profitable areas, incorporating conservation management that breaks even (e.g., planting low-input perennials), into low-yielding portions of fields could increase overall cropland profitability by 80%. This approach is applicable to the broader region and differs substantially from the status quo of ‘top-down’ land management for conservation by harnessing private interest to align profitability with the production of ecosystem services.

  4. Trophic hierarchies revealed via amino acid isotopic analysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Despite the potential of isotopic methods to illuminate trophic function, accurate estimates of lifetime feeding tendencies have remained elusive. A relatively new approach—referred to as compound-specific isotopic analysis (CSIA)—has emerged, centering on the measurement of 15N:14N ratios in amino ...

  5. Analysis of copy number variations reveals differences among cattle breeds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic structural variation is an important and abundant source of genetic and phenotypic variation. Here we describe the first systematic and genome-wide analysis of copy number variations (CNVs) in the modern domesticated cattle using array comparative genomic hybridization (array CGH) and quanti...

  6. Interindividual variability in auditory scene analysis revealed by confidence judgements.

    PubMed

    Pelofi, C; de Gardelle, V; Egré, P; Pressnitzer, D

    2017-02-19

    Because musicians are trained to discern sounds within complex acoustic scenes, such as an orchestra playing, it has been hypothesized that musicianship improves general auditory scene analysis abilities. Here, we compared musicians and non-musicians in a behavioural paradigm using ambiguous stimuli, combining performance, reaction times and confidence measures. We used 'Shepard tones', for which listeners may report either an upward or a downward pitch shift for the same ambiguous tone pair. Musicians and non-musicians performed similarly on the pitch-shift direction task. In particular, both groups were at chance for the ambiguous case. However, groups differed in their reaction times and judgements of confidence. Musicians responded to the ambiguous case with long reaction times and low confidence, whereas non-musicians responded with fast reaction times and maximal confidence. In a subsequent experiment, non-musicians displayed reduced confidence for the ambiguous case when pure-tone components of the Shepard complex were made easier to discern. The results suggest an effect of musical training on scene analysis: we speculate that musicians were more likely to discern components within complex auditory scenes, perhaps because of enhanced attentional resolution, and thus discovered the ambiguity. For untrained listeners, stimulus ambiguity was not available to perceptual awareness.This article is part of the themed issue 'Auditory and visual scene analysis'.

  7. Exceptional structured noncoding RNAs revealed by bacterial metagenome analysis.

    PubMed

    Weinberg, Zasha; Perreault, Jonathan; Meyer, Michelle M; Breaker, Ronald R

    2009-12-03

    Estimates of the total number of bacterial species indicate that existing DNA sequence databases carry only a tiny fraction of the total amount of DNA sequence space represented by this division of life. Indeed, environmental DNA samples have been shown to encode many previously unknown classes of proteins and RNAs. Bioinformatics searches of genomic DNA from bacteria commonly identify new noncoding RNAs (ncRNAs) such as riboswitches. In rare instances, RNAs that exhibit more extensive sequence and structural conservation across a wide range of bacteria are encountered. Given that large structured RNAs are known to carry out complex biochemical functions such as protein synthesis and RNA processing reactions, identifying more RNAs of great size and intricate structure is likely to reveal additional biochemical functions that can be achieved by RNA. We applied an updated computational pipeline to discover ncRNAs that rival the known large ribozymes in size and structural complexity or that are among the most abundant RNAs in bacteria that encode them. These RNAs would have been difficult or impossible to detect without examining environmental DNA sequences, indicating that numerous RNAs with extraordinary size, structural complexity, or other exceptional characteristics remain to be discovered in unexplored sequence space.

  8. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes

    PubMed Central

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-01-01

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to “phenylpropanoid biosynthesis”, “tyrosine metabolism”, “flavonoid biosynthesis”, “ascorbate and aldarate metabolism”, “betalains biosynthesis” and “anthocyanin biosynthesis”. In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level. PMID:27690004

  9. Proteomics Analysis Reveals Previously Uncharacterized Virulence Factors in Vibrio proteolyticus

    PubMed Central

    Ray, Ann; Kinch, Lisa N.; de Souza Santos, Marcela; Grishin, Nick V.

    2016-01-01

    ABSTRACT Members of the genus Vibrio include many pathogens of humans and marine animals that share genetic information via horizontal gene transfer. Hence, the Vibrio pan-genome carries the potential to establish new pathogenic strains by sharing virulence determinants, many of which have yet to be characterized. Here, we investigated the virulence properties of Vibrio proteolyticus, a Gram-negative marine bacterium previously identified as part of the Vibrio consortium isolated from diseased corals. We found that V. proteolyticus causes actin cytoskeleton rearrangements followed by cell lysis in HeLa cells in a contact-independent manner. In search of the responsible virulence factor involved, we determined the V. proteolyticus secretome. This proteomics approach revealed various putative virulence factors, including active type VI secretion systems and effectors with virulence toxin domains; however, these type VI secretion systems were not responsible for the observed cytotoxic effects. Further examination of the V. proteolyticus secretome led us to hypothesize and subsequently demonstrate that a secreted hemolysin, belonging to a previously uncharacterized clan of the leukocidin superfamily, was the toxin responsible for the V. proteolyticus-mediated cytotoxicity in both HeLa cells and macrophages. Clearly, there remains an armory of yet-to-be-discovered virulence factors in the Vibrio pan-genome that will undoubtedly provide a wealth of knowledge on how a pathogen can manipulate host cells. PMID:27460800

  10. Quantitative proteomic analysis reveals posttranslational responses to aneuploidy in yeast

    PubMed Central

    Dephoure, Noah; Hwang, Sunyoung; O'Sullivan, Ciara; Dodgson, Stacie E; Gygi, Steven P; Amon, Angelika; Torres, Eduardo M

    2014-01-01

    Aneuploidy causes severe developmental defects and is a near universal feature of tumor cells. Despite its profound effects, the cellular processes affected by aneuploidy are not well characterized. Here, we examined the consequences of aneuploidy on the proteome of aneuploid budding yeast strains. We show that although protein levels largely scale with gene copy number, subunits of multi-protein complexes are notable exceptions. Posttranslational mechanisms attenuate their expression when their encoding genes are in excess. Our proteomic analyses further revealed a novel aneuploidy-associated protein expression signature characteristic of altered metabolism and redox homeostasis. Indeed aneuploid cells harbor increased levels of reactive oxygen species (ROS). Interestingly, increased protein turnover attenuates ROS levels and this novel aneuploidy-associated signature and improves the fitness of most aneuploid strains. Our results show that aneuploidy causes alterations in metabolism and redox homeostasis. Cells respond to these alterations through both transcriptional and posttranscriptional mechanisms. DOI: http://dx.doi.org/10.7554/eLife.03023.001 PMID:25073701

  11. Integrative network analysis reveals molecular mechanisms of blood pressure regulation

    PubMed Central

    Huan, Tianxiao; Meng, Qingying; Saleh, Mohamed A; Norlander, Allison E; Joehanes, Roby; Zhu, Jun; Chen, Brian H; Zhang, Bin; Johnson, Andrew D; Ying, Saixia; Courchesne, Paul; Raghavachari, Nalini; Wang, Richard; Liu, Poching; O'Donnell, Christopher J; Vasan, Ramachandran; Munson, Peter J; Madhur, Meena S; Harrison, David G; Yang, Xia; Levy, Daniel

    2015-01-01

    Genome-wide association studies (GWAS) have identified numerous loci associated with blood pressure (BP). The molecular mechanisms underlying BP regulation, however, remain unclear. We investigated BP-associated molecular mechanisms by integrating BP GWAS with whole blood mRNA expression profiles in 3,679 individuals, using network approaches. BP transcriptomic signatures at the single-gene and the coexpression network module levels were identified. Four coexpression modules were identified as potentially causal based on genetic inference because expression-related SNPs for their corresponding genes demonstrated enrichment for BP GWAS signals. Genes from the four modules were further projected onto predefined molecular interaction networks, revealing key drivers. Gene subnetworks entailing molecular interactions between key drivers and BP-related genes were uncovered. As proof-of-concept, we validated SH2B3, one of the top key drivers, using Sh2b3−/− mice. We found that a significant number of genes predicted to be regulated by SH2B3 in gene networks are perturbed in Sh2b3−/− mice, which demonstrate an exaggerated pressor response to angiotensin II infusion. Our findings may help to identify novel targets for the prevention or treatment of hypertension. PMID:25882670

  12. Genomic analysis reveals selection in Chinese native black pig

    PubMed Central

    Fu, Yuhua; Li, Cencen; Tang, Qianzi; Tian, Shilin; Jin, Long; Chen, Jianhai; Li, Mingzhou; Li, Changchun

    2016-01-01

    Identification of genomic signatures that help reveal mechanisms underlying desirable traits in domesticated pigs is of significant biological, agricultural and medical importance. To identify the genomic footprints left by selection during domestication of the Enshi black pig, a typical native and meat-lard breed in China, we generated about 72-fold coverage of the pig genome using pools of genomic DNA representing three different populations of Enshi black pigs from three different locations. Combining this data with the available whole genomes of 13 Chinese wild boars, we identified 417 protein-coding genes embedded in the selected regions of Enshi black pigs. These genes are mainly involved in developmental and metabolic processes, response to stimulus, and other biological processes. Signatures of selection were detected in genes involved in body size and immunity (RPS10 and VASN), lipid metabolism (GSK3), male fertility (INSL6) and developmental processes (TBX19). These findings provide a window into the potential genetic mechanism underlying development of desirable phenotypes in Enshi black pigs during domestication and subsequent artificial selection. Thus, our results illustrate how domestication has shaped patterns of genetic variation in Enshi black pigs and provide valuable genetic resources that enable effective use of pigs in agricultural production. PMID:27808243

  13. Multiple etiologies for Alzheimer disease are revealed by segregation analysis

    SciTech Connect

    Rao, V.S.; Connor-Lacke, L.; Cupplies, L.A.; Growdon, J.H.; Farrer, L.A.; Duijn, C.M. van

    1994-11-01

    We have evaluated several transmission models for Alzheimer disease (AD), using the logistic regressive approach in 401 nuclear families of consecutively ascertained and rigorously diagnosed probands. Models postulating no major gene effect, random environmental transmission, recessive inheritance, and sporadic occurrence were rejected under varied assumptions regarding the associations among sex, age, and major gene susceptibility. Transmission of the disorder was not fully explained by a single Mendelian model for all families. Stratification of families as early- and late-onset by using the median of family mean onset ages showed that, regardless of the model studied, two groups of families fit better than a single group. AD in early-onset families is transmitted as an autosomal dominant trait with full penetrance in both sexes and has a gene frequency of 1.5%. Dominant inheritance also gave the best fit of the data in late-onset families, but this hypothesis was rejected, suggesting the presence of heterogeneity within this subset. Our study also revealed that genetically nonsusceptible males and females develop AD, indicating the presence of phenocopies within early-onset and late-onset groups. Moreover, our results suggest that the higher risk to females is not solely due to their increased longevity. 50 refs., 5 tabs.

  14. Comparative Genomic Analysis Reveals Ecological Differentiation in the Genus Carnobacterium

    PubMed Central

    Iskandar, Christelle F.; Borges, Frédéric; Taminiau, Bernard; Daube, Georges; Zagorec, Monique; Remenant, Benoît; Leisner, Jørgen J.; Hansen, Martin A.; Sørensen, Søren J.; Mangavel, Cécile; Cailliez-Grimal, Catherine; Revol-Junelles, Anne-Marie

    2017-01-01

    Lactic acid bacteria (LAB) differ in their ability to colonize food and animal-associated habitats: while some species are specialized and colonize a limited number of habitats, other are generalist and are able to colonize multiple animal-linked habitats. In the current study, Carnobacterium was used as a model genus to elucidate the genetic basis of these colonization differences. Analyses of 16S rRNA gene meta-barcoding data showed that C. maltaromaticum followed by C. divergens are the most prevalent species in foods derived from animals (meat, fish, dairy products), and in the gut. According to phylogenetic analyses, these two animal-adapted species belong to one of two deeply branched lineages. The second lineage contains species isolated from habitats where contact with animal is rare. Genome analyses revealed that members of the animal-adapted lineage harbor a larger secretome than members of the other lineage. The predicted cell-surface proteome is highly diversified in C. maltaromaticum and C. divergens with genes involved in adaptation to the animal milieu such as those encoding biopolymer hydrolytic enzymes, a heme uptake system, and biopolymer-binding adhesins. These species also exhibit genes for gut adaptation and respiration. In contrast, Carnobacterium species belonging to the second lineage encode a poorly diversified cell-surface proteome, lack genes for gut adaptation and are unable to respire. These results shed light on the important genomics traits required for adaptation to animal-linked habitats in generalist Carnobacterium. PMID:28337181

  15. Proteomic Analysis of Hylocereus polyrhizus Reveals Metabolic Pathway Changes.

    PubMed

    Hua, Qingzhu; Zhou, Qianjun; Gan, Susheng; Wu, Jingyu; Chen, Canbin; Li, Jiaqiang; Ye, Yaoxiong; Zhao, Jietang; Hu, Guibing; Qin, Yonghua

    2016-09-28

    Red dragon fruit or red pitaya (Hylocereus polyrhizus) is the only edible fruit that contains betalains. The color of betalains ranges from red and violet to yellow in plants. Betalains may also serve as an important component of health-promoting and disease-preventing functional food. Currently, the biosynthetic and regulatory pathways for betalain production remain to be fully deciphered. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analyses were used to reveal the molecular mechanism of betalain biosynthesis in H. polyrhizus fruits at white and red pulp stages, respectively. A total of 1946 proteins were identified as the differentially expressed between the two samples, and 936 of them were significantly highly expressed at the red pulp stage of H. polyrhizus. RNA-seq and iTRAQ analyses showed that some transcripts and proteins were positively correlated; they belonged to "phenylpropanoid biosynthesis", "tyrosine metabolism", "flavonoid biosynthesis", "ascorbate and aldarate metabolism", "betalains biosynthesis" and "anthocyanin biosynthesis". In betalains biosynthesis pathway, several proteins/enzymes such as polyphenol oxidase, CYP76AD3 and 4,5-dihydroxy-phenylalanine (DOPA) dioxygenase extradiol-like protein were identified. The present study provides a new insight into the molecular mechanism of the betalain biosynthesis at the posttranscriptional level.

  16. Global Analysis of ATM Polymorphism Reveals Significant Functional Constraint

    PubMed Central

    Thorstenson, Yvonne R.; Shen, Peidong; Tusher, Virginia G.; Wayne, Tierney L.; Davis, Ronald W.; Chu, Gilbert; Oefner, Peter J.

    2001-01-01

    ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive survey of sequence variation in ATM in diverse human populations. The protein-encoding exons of the gene (9,168 bp) and the adjacent intron and untranslated sequences (14,661 bp) were analyzed in 93 individuals from seven major human populations. In addition, the coding sequence was analyzed in one chimpanzee, one gorilla, one orangutan, and one Old World monkey. In human ATM, 88 variant sites were discovered by denaturing high-performance liquid chromatography, which is 96%–100% sensitive for detection of DNA sequence variation. ATM was compared to 14 other autosomal genes for nucleotide diversity. The noncoding regions of ATM had diversity values comparable to other genes, but the coding regions had very low diversity, especially in the last 29% of the protein sequence. A test of the neutral evolution hypothesis, through use of the Hudson/Kreitman/Aguadé statistic, revealed that this region of the human ATM gene was significantly constrained relative to that of the orangutan, the Old World monkey, and the mouse, but not relative to that of the chimpanzee or the gorilla. ATM displayed extensive linkage disequilibrium, consistent with suppression of meiotic recombination at this locus. Seven haplotypes were defined. Two haplotypes accounted for 82% of all chromosomes analyzed in all major populations; two others carrying the same D126E missense polymorphism accounted for 33% of chromosomes in Africa but were never observed outside of Africa. The high frequency of this polymorphism may be due either to a population expansion within Africa or to selective pressure. PMID:11443540

  17. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes

    PubMed Central

    Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G.; Ang, Ching-Seng; Mathivanan, Suresh

    2015-01-01

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients. PMID:25944692

  18. Proteogenomic analysis reveals exosomes are more oncogenic than ectosomes.

    PubMed

    Keerthikumar, Shivakumar; Gangoda, Lahiru; Liem, Michael; Fonseka, Pamali; Atukorala, Ishara; Ozcitti, Cemil; Mechler, Adam; Adda, Christopher G; Ang, Ching-Seng; Mathivanan, Suresh

    2015-06-20

    Extracellular vesicles (EVs) include the exosomes (30-100 nm) that are produced through the endocytic pathway via the multivesicular bodies and the ectosomes (100-1000 nm) that are released through the budding of the plasma membrane. Despite the differences in the mode of biogenesis and size, reliable markers that can distinguish between exosomes and ectosomes are non-existent. Moreover, the precise functional differences between exosomes and ectosomes remains poorly characterised. Here, using label-free quantitative proteomics, we highlight proteins that could be exploited as markers to discriminate between exosomes and ectosomes. For the first time, a global proteogenomics analysis unveiled the secretion of mutant proteins that are implicated in cancer progression through tumor-derived EVs. Follow up integrated bioinformatics analysis highlighted the enrichment of oncogenic cargo in exosomes and ectosomes. Interestingly, exosomes induced significant cell proliferation and migration in recipient cells compared to ectosomes confirming the oncogenic nature of exosomes. These findings ascertain that cancer cells facilitate oncogenesis by the secretion of mutant and oncoproteins into the tumor microenvironment via exosomes and ectosomes. The integrative proteogenomics approach utilized in this study has the potential to identify disease biomarker candidates which can be later assayed in liquid biopsies obtained from cancer patients.

  19. Network analysis reveals potential markers for pediatric adrenocortical carcinoma

    PubMed Central

    Kulshrestha, Anurag; Suman, Shikha; Ranjan, Rakesh

    2016-01-01

    Pediatric adrenocortical carcinoma (ACC) is a rare malignancy with a poor outcome. Molecular mechanisms of pediatric ACC oncogenesis and advancement are not well understood. Accurate and timely diagnosis of the disease requires identification of new markers for pediatric ACC. Differentially expressed genes (DEGs) were identified from the gene expression profile of pediatric ACC and obtained from Gene Expression Omnibus. Gene Ontology functional and pathway enrichment analysis was implemented to recognize the functions of DEGs. A protein–protein interaction (PPI) and gene–gene functional interaction (GGI) network of DEGs was constructed. Hub gene detection and enrichment analysis of functional modules were performed. Furthermore, a gene regulatory network incorporating DEGs–microRNAs–transcription factors was constructed and analyzed. A total of 431 DEGs including 228 upregulated and 203 downregulated DEGs were screened. These genes were largely involved in cell cycle, steroid biosynthesis, and p53 signaling pathways. Upregulated genes, CDK1, CCNB1, CDC20, and BUB1B, were identified as the common hubs of PPI and GGI networks. All the four common hub genes were also part of modules of the PPI network. Moreover, all the four genes were also present in the largest module of GGI network. A gene regulatory network consisting of 82 microRNAs and 100 transcription factors was also constructed. CDK1, CCNB1, CDC20, and BUB1B may serve as potential biomarker of pediatric ACC and as potential targets for therapeutic approach, although experimental studies are required to authenticate our findings. PMID:27555782

  20. Gas Hydrate-Sediment Morphologies Revealed by Pressure Core Analysis

    NASA Astrophysics Data System (ADS)

    Holland, M.; Schultheiss, P.; Roberts, J.; Druce, M.

    2006-12-01

    Analysis of HYACINTH pressure cores collected on IODP Expedition 311 and NGHP Expedition 1 showed gas hydrate layers, lenses, and veins contained in fine-grained sediments as well as gas hydrate contained in coarse-grained layers. Pressure cores were recovered from sediments on the Cascadia Margin off the North American West Coast and in the Krishna-Godavari Basin in the Western Bay of Bengal in water depths of 800- 1400 meters. Recovered cores were transferred to laboratory chambers without loss of pressure and nondestructive measurements were made at in situ pressures and controlled temperatures. Gamma density, P-wave velocity, and X-ray images showed evidence of grain-displacing and pore-filling gas hydrate in the cores. Data highlights include X-ray images of fine-grained sediment cores showing wispy subvertical veins of gas hydrate and P-wave velocity excursions corresponding to grain-displacing layers and pore-filling layers of gas hydrate. Most cores were subjected to controlled depressurization experiments, where expelled gas was collected, analyzed for composition, and used to calculate gas hydrate saturation within the core. Selected cores were stored under pressure for postcruise analysis and subsampling.

  1. Genomic analysis of regulatory network dynamics reveals large topological changes

    NASA Astrophysics Data System (ADS)

    Luscombe, Nicholas M.; Madan Babu, M.; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A.; Gerstein, Mark

    2004-09-01

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here-particularly the large-scale topological changes and hub transience-will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  2. Genomic analysis of regulatory network dynamics reveals large topological changes.

    PubMed

    Luscombe, Nicholas M; Babu, M Madan; Yu, Haiyuan; Snyder, Michael; Teichmann, Sarah A; Gerstein, Mark

    2004-09-16

    Network analysis has been applied widely, providing a unifying language to describe disparate systems ranging from social interactions to power grids. It has recently been used in molecular biology, but so far the resulting networks have only been analysed statically. Here we present the dynamics of a biological network on a genomic scale, by integrating transcriptional regulatory information and gene-expression data for multiple conditions in Saccharomyces cerevisiae. We develop an approach for the statistical analysis of network dynamics, called SANDY, combining well-known global topological measures, local motifs and newly derived statistics. We uncover large changes in underlying network architecture that are unexpected given current viewpoints and random simulations. In response to diverse stimuli, transcription factors alter their interactions to varying degrees, thereby rewiring the network. A few transcription factors serve as permanent hubs, but most act transiently only during certain conditions. By studying sub-network structures, we show that environmental responses facilitate fast signal propagation (for example, with short regulatory cascades), whereas the cell cycle and sporulation direct temporal progression through multiple stages (for example, with highly inter-connected transcription factors). Indeed, to drive the latter processes forward, phase-specific transcription factors inter-regulate serially, and ubiquitously active transcription factors layer above them in a two-tiered hierarchy. We anticipate that many of the concepts presented here--particularly the large-scale topological changes and hub transience--will apply to other biological networks, including complex sub-systems in higher eukaryotes.

  3. Genome analysis of the platypus reveals unique signatures of evolution.

    PubMed

    Warren, Wesley C; Hillier, LaDeana W; Marshall Graves, Jennifer A; Birney, Ewan; Ponting, Chris P; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P; Miethke, Pat; Waters, Paul D; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S; López-Otín, Carlos; Ordóñez, Gonzalo R; Eichler, Evan E; Chen, Lin; Cheng, Ze; Deakin, Janine E; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T; Wakefield, Matthew J; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A; Smit, Arian F A; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A; Walker, Jerilyn A; Konkel, Miriam K; Harris, Robert S; Whittington, Camilla M; Wong, Emily S W; Gemmell, Neil J; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M; Sharp, Julie A; Nicholas, Kevin R; Ray, David A; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H; Taylor, James; Jones, Russell C; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N; Pohl, Craig S; Smith, Scott M; Hou, Shunfeng; Nefedov, Mikhail; de Jong, Pieter J; Renfree, Marilyn B; Mardis, Elaine R; Wilson, Richard K

    2008-05-08

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.

  4. Image analysis of weaverbird nests reveals signature weave textures.

    PubMed

    Bailey, Ida E; Backes, André; Walsh, Patrick T; Morgan, Kate V; Meddle, Simone L; Healy, Susan D

    2015-06-01

    In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests.

  5. Image analysis of weaverbird nests reveals signature weave textures

    PubMed Central

    Bailey, Ida E.; Backes, André; Walsh, Patrick T.; Morgan, Kate V.; Meddle, Simone L.; Healy, Susan D.

    2015-01-01

    In nature, many animals build structures that can be readily measured at the scale of their gross morphology (e.g. length, volume and weight). Capturing individuality as can be done with the structures designed and built by human architects or artists, however, is more challenging. Here, we tested whether computer-aided image texture classification approaches can be used to describe textural variation in the nests of weaverbirds (Ploceus species) in order to attribute nests to the individual weaverbird that built them. We found that a computer-aided texture analysis approach does allow the assignment of a signature to weaverbirds' nests. We suggest that this approach will be a useful tool with which to examine individual variation across a range of animal constructions, not just for nests. PMID:26543586

  6. Genome analysis of the platypus reveals unique signatures of evolution

    PubMed Central

    Warren, Wesley C.; Hillier, LaDeana W.; Marshall Graves, Jennifer A.; Birney, Ewan; Ponting, Chris P.; Grützner, Frank; Belov, Katherine; Miller, Webb; Clarke, Laura; Chinwalla, Asif T.; Yang, Shiaw-Pyng; Heger, Andreas; Locke, Devin P.; Miethke, Pat; Waters, Paul D.; Veyrunes, Frédéric; Fulton, Lucinda; Fulton, Bob; Graves, Tina; Wallis, John; Puente, Xose S.; López-Otín, Carlos; Ordóñez, Gonzalo R.; Eichler, Evan E.; Chen, Lin; Cheng, Ze; Deakin, Janine E.; Alsop, Amber; Thompson, Katherine; Kirby, Patrick; Papenfuss, Anthony T.; Wakefield, Matthew J.; Olender, Tsviya; Lancet, Doron; Huttley, Gavin A.; Smit, Arian F. A.; Pask, Andrew; Temple-Smith, Peter; Batzer, Mark A.; Walker, Jerilyn A.; Konkel, Miriam K.; Harris, Robert S.; Whittington, Camilla M.; Wong, Emily S. W.; Gemmell, Neil J.; Buschiazzo, Emmanuel; Vargas Jentzsch, Iris M.; Merkel, Angelika; Schmitz, Juergen; Zemann, Anja; Churakov, Gennady; Kriegs, Jan Ole; Brosius, Juergen; Murchison, Elizabeth P.; Sachidanandam, Ravi; Smith, Carly; Hannon, Gregory J.; Tsend-Ayush, Enkhjargal; McMillan, Daniel; Attenborough, Rosalind; Rens, Willem; Ferguson-Smith, Malcolm; Lefèvre, Christophe M.; Sharp, Julie A.; Nicholas, Kevin R.; Ray, David A.; Kube, Michael; Reinhardt, Richard; Pringle, Thomas H.; Taylor, James; Jones, Russell C.; Nixon, Brett; Dacheux, Jean-Louis; Niwa, Hitoshi; Sekita, Yoko; Huang, Xiaoqiu; Stark, Alexander; Kheradpour, Pouya; Kellis, Manolis; Flicek, Paul; Chen, Yuan; Webber, Caleb; Hardison, Ross; Nelson, Joanne; Hallsworth-Pepin, Kym; Delehaunty, Kim; Markovic, Chris; Minx, Pat; Feng, Yucheng; Kremitzki, Colin; Mitreva, Makedonka; Glasscock, Jarret; Wylie, Todd; Wohldmann, Patricia; Thiru, Prathapan; Nhan, Michael N.; Pohl, Craig S.; Smith, Scott M.; Hou, Shunfeng; Renfree, Marilyn B.; Mardis, Elaine R.; Wilson, Richard K.

    2009-01-01

    We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation. PMID:18464734

  7. Time-Frequency Analysis Reveals Pairwise Interactions in Insect Swarms

    NASA Astrophysics Data System (ADS)

    Puckett, James G.; Ni, Rui; Ouellette, Nicholas T.

    2015-06-01

    The macroscopic emergent behavior of social animal groups is a classic example of dynamical self-organization, and is thought to arise from the local interactions between individuals. Determining these interactions from empirical data sets of real animal groups, however, is challenging. Using multicamera imaging and tracking, we studied the motion of individual flying midges in laboratory mating swarms. By performing a time-frequency analysis of the midge trajectories, we show that the midge behavior can be segmented into two distinct modes: one that is independent and composed of low-frequency maneuvers, and one that consists of higher-frequency nearly harmonic oscillations conducted in synchrony with another midge. We characterize these pairwise interactions, and make a hypothesis as to their biological function.

  8. Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis

    PubMed Central

    Irie, Naoki; Kuratani, Shigeru

    2011-01-01

    One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates. PMID:21427719

  9. Kidney tumor biomarkers revealed by simultaneous multiple matrix metabolomics analysis.

    PubMed

    Ganti, Sheila; Taylor, Sandra L; Abu Aboud, Omran; Yang, Joy; Evans, Christopher; Osier, Michael V; Alexander, Danny C; Kim, Kyoungmi; Weiss, Robert H

    2012-07-15

    Metabolomics is increasingly being used in cancer biology for biomarker discovery and identification of potential novel therapeutic targets. However, a systematic metabolomics study of multiple biofluids to determine their interrelationships and to describe their use as tumor proxies is lacking. Using a mouse xenograft model of kidney cancer, characterized by subcapsular implantation of Caki-1 clear cell human kidney cancer cells, we examined tissue, serum, and urine all obtained simultaneously at baseline (urine) and at, or close to, animal sacrifice (urine, tissue, and plasma). Uniform metabolomics analysis of all three "matrices" was accomplished using gas chromatography- and liquid chromatography-mass spectrometry. Of all the metabolites identified (267 in tissue, 246 in serum, and 267 in urine), 89 were detected in all 3 matrices, and the majority was altered in the same direction. Heat maps of individual metabolites showed that alterations in serum were more closely related to tissue than was urine. Two metabolites, cinnamoylglycine and nicotinamide, were concordantly and significantly (when corrected for multiple testing) altered in tissue and serum, and cysteine-glutathione disulfide showed the highest change (232.4-fold in tissue) of any metabolite. On the basis of these and other considerations, three pathways were chosen for biologic validation of the metabolomic data, resulting in potential therapeutic target identification. These data show that serum metabolomics analysis is a more accurate proxy for tissue changes than urine and that tryptophan degradation (yielding anti-inflammatory metabolites) is highly represented in renal cell carcinoma, and support the concept that PPAR-α antagonism may be a potential therapeutic approach for this disease.

  10. Hormone therapy and radiotherapy for early prostate cancer: A utility-adjusted number needed to treat (NNT) analysis

    SciTech Connect

    Jani, Ashesh B.; Kao, Johnny; Heimann, Ruth; Hellman, Samuel . E-mail: s-hellman@uchicago.edu

    2005-03-01

    Purpose: To quantify, using the number needed to treat (NNT) methodology, the benefit of short-term ({<=}6 months) hormone therapy adjuvant to radiotherapy in the group of patients with early (clinical stage T1-T2c) prostate cancer. Methods and materials: The absolute biochemical control benefit for the use of hormones adjuvant to radiotherapy in early-stage disease was determined by literature review. A model was developed to estimate the utility-adjusted survival detriment due to the side effects of hormone therapy. The NNTs before and after the incorporation of hormone sequelae were computed; the sign and magnitude of the NNTs were used to gauge the effect of the hormones. Results: The absolute NNT analysis, based on summarizing the results of 8 reports including a total of 3652 patients, demonstrated an advantage to the addition of hormones for the general early-stage prostate cancer population as well as for all prognostic groups. After adjustment for hormone-induced functional loss, the advantage of hormones remained considerable in the high- and intermediate-risk groups, with the utility-adjusted NNT becoming weakened in the low-risk group when the utility compromise from complications of hormones was assumed to be considerable. Conclusions: Short-term hormone therapy seems to be beneficial for selected early-stage prostate cancer patients. The advantage seems to be greatest in the intermediate- and high-risk groups; with current follow-up, the side effects of hormones may outweigh their benefit in certain clinical situations in the favorable group. The present investigation demonstrates the significant role of the NNT technique for oncologic and radiotherapeutic management decisions when treatment complications need to be considered and balanced with the beneficial effects of the treatment.

  11. Cost analysis of adjustments of the epidemiological surveillance system to mass gatherings.

    PubMed

    Zieliński, Andrzej

    2011-01-01

    The article deals with the problem of economical analysis of public health activities at mass gatherings. After presentation of elementary review of basic economical approaches to cost analysis author tries to analyze applicability of those methods to planning of mass gatherings. Difficulties in comparability of different events and lack of the outcome data at the stage of planning make most of the economic approaches unsuitable to application at the planning stage. Even applicability of cost minimization analysis may be limited to comparison of predicted costs of preconceived standards of epidemiological surveillance. Cost effectiveness performed ex post after the event when both costs and obtained effects are known, may bring more information for future selection of most effective procedures.

  12. Differential network analysis reveals dysfunctional regulatory networks in gastric carcinogenesis

    PubMed Central

    Cao, Mu-Shui; Liu, Bing-Ya; Dai, Wen-Tao; Zhou, Wei-Xin; Li, Yi-Xue; Li, Yuan-Yuan

    2015-01-01

    Gastric Carcinoma is one of the most common cancers in the world. A large number of differentially expressed genes have been identified as being associated with gastric cancer progression, however, little is known about the underlying regulatory mechanisms. To address this problem, we developed a differential networking approach that is characterized by including a nascent methodology, differential coexpression analysis (DCEA), and two novel quantitative methods for differential regulation analysis. We first applied DCEA to a gene expression dataset of gastric normal mucosa, adenoma and carcinoma samples to identify gene interconnection changes during cancer progression, based on which we inferred normal, adenoma, and carcinoma-specific gene regulation networks by using linear regression model. It was observed that cancer genes and drug targets were enriched in each network. To investigate the dynamic changes of gene regulation during carcinogenesis, we then designed two quantitative methods to prioritize differentially regulated genes (DRGs) and gene pairs or links (DRLs) between adjacent stages. It was found that known cancer genes and drug targets are significantly higher ranked. The top 4% normal vs. adenoma DRGs (36 genes) and top 6% adenoma vs. carcinoma DRGs (56 genes) proved to be worthy of further investigation to explore their association with gastric cancer. Out of the 16 DRGs involved in two top-10 DRG lists of normal vs. adenoma and adenoma vs. carcinoma comparisons, 15 have been reported to be gastric cancer or cancer related. Based on our inferred differential networking information and known signaling pathways, we generated testable hypotheses on the roles of GATA6, ESRRG and their signaling pathways in gastric carcinogenesis. Compared with established approaches which build genome-scale GRNs, or sub-networks around differentially expressed genes, the present one proved to be better at enriching cancer genes and drug targets, and prioritizing

  13. Phylogenetic analysis reveals a scattered distribution of autumn colours

    PubMed Central

    Archetti, Marco

    2009-01-01

    Background and Aims Leaf colour in autumn is rarely considered informative for taxonomy, but there is now growing interest in the evolution of autumn colours and different hypotheses are debated. Research efforts are hindered by the lack of basic information: the phylogenetic distribution of autumn colours. It is not known when and how autumn colours evolved. Methods Data are reported on the autumn colours of 2368 tree species belonging to 400 genera of the temperate regions of the world, and an analysis is made of their phylogenetic relationships in order to reconstruct the evolutionary origin of red and yellow in autumn leaves. Key Results Red autumn colours are present in at least 290 species (70 genera), and evolved independently at least 25 times. Yellow is present independently from red in at least 378 species (97 genera) and evolved at least 28 times. Conclusions The phylogenetic reconstruction suggests that autumn colours have been acquired and lost many times during evolution. This scattered distribution could be explained by hypotheses involving some kind of coevolutionary interaction or by hypotheses that rely on the need for photoprotection. PMID:19126636

  14. A graphical analysis revealed frailty deficits aggregate and are multidimensional

    PubMed Central

    Sourial, Nadia; Wolfson, Christina; Bergman, Howard; Zhu, Bin; Karunananthan, Sathya; Quail, Jacqueline; Fletcher, John; Weiss, Deborah; Bandeen-Roche, Karen; Béland, François

    2013-01-01

    Objective To examine the relationships among seven frailty domains: nutrition, physical activity, mobility, strength, energy, cognition, and mood, using data from three studies. Study Design and Setting Data from three studies were separately analyzed using Multiple Correspondence Analysis (MCA). The graphical output of MCA was used to assess 1) if the presence of deficits in the frailty domains separate from the absence of deficits on the graph, 2) the dimensionality of the domains, 3) the clustering of domains within each dimension and 4) their relationship with age, sex and disability. Results were compared across the studies. Results In two studies, presence of deficits for all domains separated from absence of deficits. In the third study, there was separation in all domains except cognition. Three main dimensions were retained in each study however assigned dimensionality of domains differed. The clustering of mobility with energy and/or strength was consistent across studies. Deficits were associated with older age, female sex and disability. Conclusion Our results suggest that frailty is a multidimensional concept for which the relationships among domains differ according to the population characteristics. These domains, with the possible exception of cognition, appear to aggregate together and share a common underlying construct. PMID:19880286

  15. Network analysis reveals distinct clinical syndromes underlying acute mountain sickness.

    PubMed

    Hall, David P; MacCormick, Ian J C; Phythian-Adams, Alex T; Rzechorzek, Nina M; Hope-Jones, David; Cosens, Sorrel; Jackson, Stewart; Bates, Matthew G D; Collier, David J; Hume, David A; Freeman, Thomas; Thompson, A A Roger; Baillie, John Kenneth

    2014-01-01

    Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes.

  16. Network Analysis Reveals Distinct Clinical Syndromes Underlying Acute Mountain Sickness

    PubMed Central

    Hall, David P.; MacCormick, Ian J. C.; Phythian-Adams, Alex T.; Rzechorzek, Nina M.; Hope-Jones, David; Cosens, Sorrel; Jackson, Stewart; Bates, Matthew G. D.; Collier, David J.; Hume, David A.; Freeman, Thomas; Thompson, A. A. Roger; Baillie, John Kenneth

    2014-01-01

    Acute mountain sickness (AMS) is a common problem among visitors at high altitude, and may progress to life-threatening pulmonary and cerebral oedema in a minority of cases. International consensus defines AMS as a constellation of subjective, non-specific symptoms. Specifically, headache, sleep disturbance, fatigue and dizziness are given equal diagnostic weighting. Different pathophysiological mechanisms are now thought to underlie headache and sleep disturbance during acute exposure to high altitude. Hence, these symptoms may not belong together as a single syndrome. Using a novel visual analogue scale (VAS), we sought to undertake a systematic exploration of the symptomatology of AMS using an unbiased, data-driven approach originally designed for analysis of gene expression. Symptom scores were collected from 292 subjects during 1110 subject-days at altitudes between 3650 m and 5200 m on Apex expeditions to Bolivia and Kilimanjaro. Three distinct patterns of symptoms were consistently identified. Although fatigue is a ubiquitous finding, sleep disturbance and headache are each commonly reported without the other. The commonest pattern of symptoms was sleep disturbance and fatigue, with little or no headache. In subjects reporting severe headache, 40% did not report sleep disturbance. Sleep disturbance correlates poorly with other symptoms of AMS (Mean Spearman correlation 0.25). These results challenge the accepted paradigm that AMS is a single disease process and describe at least two distinct syndromes following acute ascent to high altitude. This approach to analysing symptom patterns has potential utility in other clinical syndromes. PMID:24465370

  17. Differential Network Analysis Reveals Genetic Effects on Catalepsy Modules

    PubMed Central

    Iancu, Ovidiu D.; Oberbeck, Denesa; Darakjian, Priscila; Kawane, Sunita; Erk, Jason; McWeeney, Shannon; Hitzemann, Robert

    2013-01-01

    We performed short-term bi-directional selective breeding for haloperidol-induced catalepsy, starting from three mouse populations of increasingly complex genetic structure: an F2 intercross, a heterogeneous stock (HS) formed by crossing four inbred strains (HS4) and a heterogeneous stock (HS-CC) formed from the inbred strain founders of the Collaborative Cross (CC). All three selections were successful, with large differences in haloperidol response emerging within three generations. Using a custom differential network analysis procedure, we found that gene coexpression patterns changed significantly; importantly, a number of these changes were concordant across genetic backgrounds. In contrast, absolute gene-expression changes were modest and not concordant across genetic backgrounds, in spite of the large and similar phenotypic differences. By inferring strain contributions from the parental lines, we are able to identify significant differences in allelic content between the selected lines concurrent with large changes in transcript connectivity. Importantly, this observation implies that genetic polymorphisms can affect transcript and module connectivity without large changes in absolute expression levels. We conclude that, in this case, selective breeding acts at the subnetwork level, with the same modules but not the same transcripts affected across the three selections. PMID:23555609

  18. Bioimage analysis of Shigella infection reveals targeting of colonic crypts.

    PubMed

    Arena, Ellen T; Campbell-Valois, Francois-Xavier; Tinevez, Jean-Yves; Nigro, Giulia; Sachse, Martin; Moya-Nilges, Maryse; Nothelfer, Katharina; Marteyn, Benoit; Shorte, Spencer L; Sansonetti, Philippe J

    2015-06-23

    Few studies within the pathogenic field have used advanced imaging and analytical tools to quantitatively measure pathogenicity in vivo. In this work, we present a novel approach for the investigation of host-pathogen processes based on medium-throughput 3D fluorescence imaging. The guinea pig model for Shigella flexneri invasion of the colonic mucosa was used to monitor the infectious process over time with GFP-expressing S. flexneri. A precise quantitative imaging protocol was devised to follow individual S. flexneri in a large tissue volume. An extensive dataset of confocal images was obtained and processed to extract specific quantitative information regarding the progression of S. flexneri infection in an unbiased and exhaustive manner. Specific parameters included the analysis of S. flexneri positions relative to the epithelial surface, S. flexneri density within the tissue, and volume of tissue destruction. In particular, at early time points, there was a clear association of S. flexneri with crypts, key morphological features of the colonic mucosa. Numerical simulations based on random bacterial entry confirmed the bias of experimentally measured S. flexneri for early crypt targeting. The application of a correlative light and electron microscopy technique adapted for thick tissue samples further confirmed the location of S. flexneri within colonocytes at the mouth of crypts. This quantitative imaging approach is a novel means to examine host-pathogen systems in a tailored and robust manner, inclusive of the infectious agent.

  19. Consanguinity and late fertility: spatial analysis reveals positive association patterns.

    PubMed

    Lisa, Antonella; Astolfi, Paola; Zei, Gianna; Tentoni, Stefania

    2015-01-01

    The role of consanguinity on human complex traits is an important and controversial issue. In this work we focused on the Sardinian population and examined the effect of consanguineous unions on late female fertility. During the last century the island has been characterized by a high incidence of marriages between relatives, favoured by socio economic conditions and geographical isolation, and by high fertility despite a widespread tendency to delay reproduction. Through spatial analysis techniques, we explored the geographical heterogeneity of consanguinity and late fertility, and identified in Central-Eastern Sardinia a common area with an excess of both traits, where the traits are positively associated. We found that their association did not significantly affect women's fertility in the area, despite the expected negative role of both traits. Intriguingly, this critical zone corresponds well to areas reported by previous studies as being peculiar for a high frequency of centenarians and for lower risk in pregnancy outcome. The proposed approach can be generally exploited to identify target populations on which socioeconomic, biodemographic and genetic data can be collected at the individual level, and deeper analyses carried out to disentangle the determinants of complex biological traits and to investigate their association.

  20. Layered Social Network Analysis Reveals Complex Relationships in Kindergarteners

    PubMed Central

    Golemiec, Mireille; Schneider, Jonathan; Boyce, W. Thomas; Bush, Nicole R.; Adler, Nancy; Levine, Joel D.

    2016-01-01

    The interplay between individuals forms building blocks for social structure. Here, we examine the structure of behavioral interactions among kindergarten classroom with a hierarchy-neutral approach to examine all possible underlying patterns in the formation of layered networks of “reciprocal” interactions. To understand how these layers are coordinated, we used a layered motif approach. Our dual layered motif analysis can therefore be thought of as the dynamics of smaller groups that tile to create the group structure, or alternatively they provide information on what the average child would do in a given local social environment. When we examine the regulated motifs in layered networks, we find that transitivity is at least partially involved in the formation of these layered network structures. We also found complex combinations of the expected reciprocal interactions. The mechanisms used to understand social networks of kindergarten children here are also applicable on a more general scale to any group of individuals where interactions and identities can be readily observed and scored. PMID:26973572

  1. Shaft adjuster

    DOEpatents

    Harry, H.H.

    1988-03-11

    Abstract and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus. 3 figs.

  2. Shaft adjuster

    DOEpatents

    Harry, Herbert H.

    1989-01-01

    Apparatus and method for the adjustment and alignment of shafts in high power devices. A plurality of adjacent rotatable angled cylinders are positioned between a base and the shaft to be aligned which when rotated introduce an axial offset. The apparatus is electrically conductive and constructed of a structurally rigid material. The angled cylinders allow the shaft such as the center conductor in a pulse line machine to be offset in any desired alignment position within the range of the apparatus.

  3. A Third Moment Adjusted Test Statistic for Small Sample Factor Analysis

    ERIC Educational Resources Information Center

    Lin, Johnny; Bentler, Peter M.

    2012-01-01

    Goodness-of-fit testing in factor analysis is based on the assumption that the test statistic is asymptotically chi-square, but this property may not hold in small samples even when the factors and errors are normally distributed in the population. Robust methods such as Browne's (1984) asymptotically distribution-free method and Satorra Bentler's…

  4. The Analysis of Repeated Measurements with Mixed-Model Adjusted "F" Tests

    ERIC Educational Resources Information Center

    Kowalchuk, Rhonda K.; Keselman, H. J.; Algina, James; Wolfinger, Russell D.

    2004-01-01

    One approach to the analysis of repeated measures data allows researchers to model the covariance structure of their data rather than presume a certain structure, as is the case with conventional univariate and multivariate test statistics. This mixed-model approach, available through SAS PROC MIXED, was compared to a Welch-James type statistic.…

  5. A Four-Step Faculty Compensation Model: From Equity Analysis to Adjustment

    ERIC Educational Resources Information Center

    Herzog, Serge

    2008-01-01

    Among the varied analytical challenges institutional researchers face, examining faculty pay may be one of the most vexing. Although the literature on faculty compensation analysis dates back to the 1970s (Loeb and Ferber, 1971; Gordon, Morton, and Braden, 1974; Scott, 1977; Braskamp and Johnson, 1978; McLaughlin, Smart, and Montgomery, 1978),…

  6. Functional Tissue Analysis Reveals Successful Cryopreservation of Human Osteoarthritic Synovium

    PubMed Central

    de Vries, Marieke; Bennink, Miranda B.; van Lent, Peter L. E. M.; van der Kraan, Peter M.; Koenders, Marije I.; Thurlings, Rogier M.; van de Loo, Fons A. J.

    2016-01-01

    Osteoarthritis (OA) is a degenerative joint disease affecting cartilage and is the most common form of arthritis worldwide. One third of OA patients have severe synovitis and less than 10% have no evidence of synovitis. Moreover, synovitis is predictive for more severe disease progression. This offers a target for therapy but more research on the pathophysiological processes in the synovial tissue of these patients is needed. Functional studies performed with synovial tissue will be more approachable when this material, that becomes available by joint replacement surgery, can be stored for later use. We set out to determine the consequences of slow-freezing of human OA synovial tissue. Therefore, we validated a method that can be applied in every routine laboratory and performed a comparative study of five cryoprotective agent (CPA) solutions. To determine possible deleterious cryopreservation-thaw effects on viability, the synovial tissue architecture, metabolic activity, RNA quality, expression of cryopreservation associated stress genes, and expression of OA characteristic disease genes was studied. Furthermore, the biological activity of the cryopreserved tissue was determined by measuring cytokine secretion induced by the TLR ligands lipopolysaccharides and Pam3Cys. Compared to non frozen synovium, no difference in cell and tissue morphology could be identified in the conditions using the CS10, standard and CryoSFM CPA solution for cryopreservation. However, we observed significantly lower preservation of tissue morphology with the Biofreeze and CS2 media. The other viability assays showed trends in the same direction but were not sensitive enough to detect significant differences between conditions. In all assays tested a clearly lower viability was detected in the condition in which synovium was frozen without CPA solution. This detailed analysis showed that OA synovial tissue explants can be cryopreserved while maintaining the morphology, viability and

  7. Neuronal Networks during Burst Suppression as Revealed by Source Analysis

    PubMed Central

    Reinicke, Christine; Moeller, Friederike; Anwar, Abdul Rauf; Mideksa, Kidist Gebremariam; Pressler, Ronit; Deuschl, Günther; Stephani, Ulrich; Siniatchkin, Michael

    2015-01-01

    Introduction Burst-suppression (BS) is an electroencephalography (EEG) pattern consisting of alternant periods of slow waves of high amplitude (burst) and periods of so called flat EEG (suppression). It is generally associated with coma of various etiologies (hypoxia, drug-related intoxication, hypothermia, and childhood encephalopathies, but also anesthesia). Animal studies suggest that both the cortex and the thalamus are involved in the generation of BS. However, very little is known about mechanisms of BS in humans. The aim of this study was to identify the neuronal network underlying both burst and suppression phases using source reconstruction and analysis of functional and effective connectivity in EEG. Material/Methods Dynamic imaging of coherent sources (DICS) was applied to EEG segments of 13 neonates and infants with burst and suppression EEG pattern. The brain area with the strongest power in the analyzed frequency (1–4 Hz) range was defined as the reference region. DICS was used to compute the coherence between this reference region and the entire brain. The renormalized partial directed coherence (RPDC) was used to describe the informational flow between the identified sources. Results/Conclusion Delta activity during the burst phases was associated with coherent sources in the thalamus and brainstem as well as bilateral sources in cortical regions mainly frontal and parietal, whereas suppression phases were associated with coherent sources only in cortical regions. Results of the RPDC analyses showed an upwards informational flow from the brainstem towards the thalamus and from the thalamus to cortical regions, which was absent during the suppression phases. These findings may support the theory that a “cortical deafferentiation” between the cortex and sub-cortical structures exists especially in suppression phases compared to burst phases in burst suppression EEGs. Such a deafferentiation may play a role in the poor neurological outcome of

  8. Network analysis reveals multiscale controls on streamwater chemistry

    USGS Publications Warehouse

    McGuire, Kevin J.; Torgersen, Christian E.; Likens, Gene E.; Buso, Donald C.; Lowe, Winsor H.; Bailey, Scott W.

    2014-01-01

    By coupling synoptic data from a basin-wide assessment of streamwater chemistry with network-based geostatistical analysis, we show that spatial processes differentially affect biogeochemical condition and pattern across a headwater stream network. We analyzed a high-resolution dataset consisting of 664 water samples collected every 100 m throughout 32 tributaries in an entire fifth-order stream network. These samples were analyzed for an exhaustive suite of chemical constituents. The fine grain and broad extent of this study design allowed us to quantify spatial patterns over a range of scales by using empirical semivariograms that explicitly incorporated network topology. Here, we show that spatial structure, as determined by the characteristic shape of the semivariograms, differed both among chemical constituents and by spatial relationship (flow-connected, flow-unconnected, or Euclidean). Spatial structure was apparent at either a single scale or at multiple nested scales, suggesting separate processes operating simultaneously within the stream network and surrounding terrestrial landscape. Expected patterns of spatial dependence for flow-connected relationships (e.g., increasing homogeneity with downstream distance) occurred for some chemical constituents (e.g., dissolved organic carbon, sulfate, and aluminum) but not for others (e.g., nitrate, sodium). By comparing semivariograms for the different chemical constituents and spatial relationships, we were able to separate effects on streamwater chemistry of (i) fine-scale versus broad-scale processes and (ii) in-stream processes versus landscape controls. These findings provide insight on the hierarchical scaling of local, longitudinal, and landscape processes that drive biogeochemical patterns in stream networks.

  9. Conformational diversity analysis reveals three functional mechanisms in proteins

    PubMed Central

    Fornasari, María Silvina

    2017-01-01

    Protein motions are a key feature to understand biological function. Recently, a large-scale analysis of protein conformational diversity showed a positively skewed distribution with a peak at 0.5 Å C-alpha root-mean-square-deviation (RMSD). To understand this distribution in terms of structure-function relationships, we studied a well curated and large dataset of ~5,000 proteins with experimentally determined conformational diversity. We searched for global behaviour patterns studying how structure-based features change among the available conformer population for each protein. This procedure allowed us to describe the RMSD distribution in terms of three main protein classes sharing given properties. The largest of these protein subsets (~60%), which we call “rigid” (average RMSD = 0.83 Å), has no disordered regions, shows low conformational diversity, the largest tunnels and smaller and buried cavities. The two additional subsets contain disordered regions, but with differential sequence composition and behaviour. Partially disordered proteins have on average 67% of their conformers with disordered regions, average RMSD = 1.1 Å, the highest number of hinges and the longest disordered regions. In contrast, malleable proteins have on average only 25% of disordered conformers and average RMSD = 1.3 Å, flexible cavities affected in size by the presence of disordered regions and show the highest diversity of cognate ligands. Proteins in each set are mostly non-homologous to each other, share no given fold class, nor functional similarity but do share features derived from their conformer population. These shared features could represent conformational mechanisms related with biological functions. PMID:28192432

  10. Metatranscriptomic Analysis of Groundwater Reveals an Active Anammox Bacterial Population

    NASA Astrophysics Data System (ADS)

    Jewell, T. N. M.; Karaoz, U.; Thomas, B. C.; Banfield, J. F.; Brodie, E.; Williams, K. H.; Beller, H. R.

    2014-12-01

    Groundwater is a major natural resource, yet little is known about the contribution of microbial anaerobic ammonium oxidation (anammox) activity to subsurface nitrogen cycling. During anammox, energy is generated as ammonium is oxidized under anaerobic conditions to dinitrogen gas, using nitrite as the final electron acceptor. This process is a global sink for fixed nitrogen. Only a narrow range of monophyletic bacteria within the Planctomycetes carries out anammox, and the full extent of their metabolism, and subsequent impact on nitrogen cycling and microbial community structure, is still unknown. Here, we employ a metatranscriptomic analysis on enriched mRNA to identify the abundance and activity of a population of anammox bacteria within an aquifer at Rifle, CO. Planktonic biomass was collected over a two-month period after injection of up to 1.5 mM nitrate. Illumina-generated sequences were mapped to a phylogenetically binned Rifle metagenome database. We identified transcripts for genes with high protein sequence identities (81-98%) to those of anammox strain KSU-1 and to two of the five anammox bacteria genera, Brocadia and Kuenenia, suggesting an active, if not diverse, anammox population. Many of the most abundant anammox transcripts mapped to a single scaffold, indicative of a single dominant anammox species. Transcripts of the genes necessary for the anammox pathway were present, including an ammonium transporter (amtB), nitrite/formate transporter, nitrite reductase (nirK), and hydrazine oxidoreductase (hzoB). The form of nitrite reductase encoded by anammox is species-dependent, and we only identified nirK, with no evidence of anammox nirS. In addition to the anammox pathway we saw evidence of the anammox bacterial dissimilatory nitrate reduction to ammonium pathway (narH, putative nrfA, and nrfB), which provides an alternate means of generating substrates for anammox from nitrate, rather than relying on an external pool. Transcripts for hydroxylamine

  11. Mutant Analysis Reveals Allosteric Regulation of ClpB Disaggregase

    PubMed Central

    Franke, Kamila B.; Bukau, Bernd; Mogk, Axel

    2017-01-01

    The members of the hexameric AAA+ disaggregase of E. coli and S. cerevisiae, ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (AAA-1, AAA-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the AAA-1 ring to downregulate ATP hydrolysis. Keeping M-domains displaced from the AAA-1 ring by association with Hsp70 increases ATPase activity due to enhanced communication between protomers. This communication involves conserved arginine fingers. The control of ClpB/Hsp104 activity is crucial, as hyperactive mutants with permanently dissociated M-domains exhibit cellular toxicity. Here, we analyzed AAA-1 inter-ring communication in relation to the M-domain mediated ATPase regulation, by subjecting a conserved residue of the AAA-1 domain subunit interface of ClpB (A328) to mutational analysis. While all A328X mutants have reduced disaggregation activities, their ATPase activities strongly differed. ClpB-A328I/L mutants have reduced ATPase activity and when combined with the hyperactive ClpB-K476C M-domain mutation, suppress cellular toxicity. This underlines that ClpB ATPase activation by M-domain dissociation relies on increased subunit communication. The ClpB-A328V mutant in contrast has very high ATPase activity and exhibits cellular toxicity on its own, qualifying it as novel hyperactive ClpB mutant. ClpB-A328V hyperactivity is however, different from that of M-domain mutants as M-domains stay associated with the AAA-1 ring. The high ATPase activity of ClpB-A328V primarily relies on the AAA-2 ring and correlates with distinct conformational changes in the AAA-2 catalytic site. These findings characterize the subunit interface residue A328 as crucial regulatory element to control ATP hydrolysis in both AAA rings. PMID:28275610

  12. Mutant Analysis Reveals Allosteric Regulation of ClpB Disaggregase.

    PubMed

    Franke, Kamila B; Bukau, Bernd; Mogk, Axel

    2017-01-01

    The members of the hexameric AAA+ disaggregase of E. coli and S. cerevisiae, ClpB, and Hsp104, cooperate with the Hsp70 chaperone system in the solubilization of aggregated proteins. Aggregate solubilization relies on a substrate threading activity of ClpB/Hsp104 fueled by ATP hydrolysis in both ATPase rings (AAA-1, AAA-2). ClpB/Hsp104 ATPase activity is controlled by the M-domains, which associate to the AAA-1 ring to downregulate ATP hydrolysis. Keeping M-domains displaced from the AAA-1 ring by association with Hsp70 increases ATPase activity due to enhanced communication between protomers. This communication involves conserved arginine fingers. The control of ClpB/Hsp104 activity is crucial, as hyperactive mutants with permanently dissociated M-domains exhibit cellular toxicity. Here, we analyzed AAA-1 inter-ring communication in relation to the M-domain mediated ATPase regulation, by subjecting a conserved residue of the AAA-1 domain subunit interface of ClpB (A328) to mutational analysis. While all A328X mutants have reduced disaggregation activities, their ATPase activities strongly differed. ClpB-A328I/L mutants have reduced ATPase activity and when combined with the hyperactive ClpB-K476C M-domain mutation, suppress cellular toxicity. This underlines that ClpB ATPase activation by M-domain dissociation relies on increased subunit communication. The ClpB-A328V mutant in contrast has very high ATPase activity and exhibits cellular toxicity on its own, qualifying it as novel hyperactive ClpB mutant. ClpB-A328V hyperactivity is however, different from that of M-domain mutants as M-domains stay associated with the AAA-1 ring. The high ATPase activity of ClpB-A328V primarily relies on the AAA-2 ring and correlates with distinct conformational changes in the AAA-2 catalytic site. These findings characterize the subunit interface residue A328 as crucial regulatory element to control ATP hydrolysis in both AAA rings.

  13. MANGO – Modal Analysis for Grid Operation: A Method for Damping Improvement through Operating Point Adjustment

    SciTech Connect

    Huang, Zhenyu; Zhou, Ning; Tuffner, Francis K.; Chen, Yousu; Trudnowski, Daniel J.; Diao, Ruisheng; Fuller, Jason C.; Mittelstadt, William A.; Hauer, John F.; Dagle, Jeffery E.

    2010-10-18

    Small signal stability problems are one of the major threats to grid stability and reliability in the U.S. power grid. An undamped mode can cause large-amplitude oscillations and may result in system breakups and large-scale blackouts. There have been several incidents of system-wide oscillations. Of those incidents, the most notable is the August 10, 1996 western system breakup, a result of undamped system-wide oscillations. Significant efforts have been devoted to monitoring system oscillatory behaviors from measurements in the past 20 years. The deployment of phasor measurement units (PMU) provides high-precision, time-synchronized data needed for detecting oscillation modes. Measurement-based modal analysis, also known as ModeMeter, uses real-time phasor measurements to identify system oscillation modes and their damping. Low damping indicates potential system stability issues. Modal analysis has been demonstrated with phasor measurements to have the capability of estimating system modes from both oscillation signals and ambient data. With more and more phasor measurements available and ModeMeter techniques maturing, there is yet a need for methods to bring modal analysis from monitoring to actions. The methods should be able to associate low damping with grid operating conditions, so operators or automated operation schemes can respond when low damping is observed. The work presented in this report aims to develop such a method and establish a Modal Analysis for Grid Operation (MANGO) procedure to aid grid operation decision making to increase inter-area modal damping. The procedure can provide operation suggestions (such as increasing generation or decreasing load) for mitigating inter-area oscillations.

  14. Self-worth and psychological adjustment of obese children: An analysis through the Draw-A-Person

    PubMed Central

    Scimeca, Giuseppe; Alborghetti, Amelia; Bruno, Antonio; Troili, Giulia Maria; Pandolfo, Gianluca; Muscatello, Maria Rosaria Anna; Zoccali, Rocco Antonio

    2016-01-01

    AIM To investigate psychopathological correlates of child obesity via the Draw-A-Person test (DAP). METHODS The participants were 50 children with a mean age of 9.74 years. Body mass index (BMI) was used as a measure of body fat. Children were divided into normal (n = 17), overweight (n = 14) and obese (n = 19). Two qualitative methods of scoring the DAP based on an integrative approach were used to assess self-concept (ESW) and overall level of children’s adjustment (EAC). A procedure for judging interpretative skills of clinicians was implemented before they evaluated children’s drawings. RESULTS As predicted by our hypothesis, BMI was negatively correlated with ESW, r (50) = -0.29, P < 0.05, but not with EAC, r (50) = - 0.08, P = ns. To evaluate the effect of gender, Pearson correlations were re-computed regrouping the sample accordingly: BMI and EAC reached a significant negative correlation in female subjects, r (24) = -0.36, P < 0.05, and a positive correlation in male subjects, r (26) = 0.37, P = < 0.05; negative correlation between BMI and ESW became stronger in females, r (24) = -0.51, P < 0.01 but not in males, whose correlation disappeared resulting not-significant, r (26) = -0.06, P = ns. No effect of age was found. Results indicate that obesity has a negative correlation exclusively on overall adjustment and self-concept in female children. CONCLUSION It was concluded that there is a negative bias toward females that reveals how the stigma of obesity is widespread in Western society. PMID:27679772

  15. Genome wide analysis of Silurana (Xenopus) tropicalis development reveals dynamic expression using network enrichment analysis.

    PubMed

    Langlois, Valérie S; Martyniuk, Christopher J

    2013-01-01

    Development involves precise timing of gene expression and coordinated pathways for organogenesis and morphogenesis. Functional and sub-network enrichment analysis provides an integrated approach for identifying networks underlying development. The objectives of this study were to characterize early gene regulatory networks over Silurana tropicalis development from NF stage 2 to 46 using a custom Agilent 4×44K microarray. There were >8000 unique gene probes that were differentially expressed between Nieuwkoop-Faber (NF) stage 2 and stage 16, and >2000 gene probes differentially expressed between NF 34 and 46. Gene ontology revealed that genes involved in nucleosome assembly, cell division, pattern specification, neurotransmission, and general metabolism were increasingly regulated throughout development, consistent with active development. Sub-network enrichment analysis revealed that processes such as membrane hyperpolarisation, retinoic acid, cholesterol, and dopamine metabolic gene networks were activated/inhibited over time. This study identifies RNA transcripts that are potentially maternally inherited in an anuran species, provides evidence that the expression of genes involved in retinoic acid receptor signaling may increase prior to those involved in thyroid receptor signaling, and characterizes novel gene expression networks preceding organogenesis which increases understanding of the spatiotemporal embryonic development in frogs.

  16. Adjusting stream-sediment geochemical maps in the Austrian Bohemian Massif by analysis of variance

    USGS Publications Warehouse

    Davis, J.C.; Hausberger, G.; Schermann, O.; Bohling, G.

    1995-01-01

    The Austrian portion of the Bohemian Massif is a Precambrian terrane composed mostly of highly metamorphosed rocks intruded by a series of granitoids that are petrographically similar. Rocks are exposed poorly and the subtle variations in rock type are difficult to map in the field. A detailed geochemical survey of stream sediments in this region has been conducted and included as part of the Geochemischer Atlas der Republik O??sterreich, and the variations in stream sediment composition may help refine the geological interpretation. In an earlier study, multivariate analysis of variance (MANOVA) was applied to the stream-sediment data in order to minimize unwanted sampling variation and emphasize relationships between stream sediments and rock types in sample catchment areas. The estimated coefficients were used successfully to correct for the sampling effects throughout most of the region, but also introduced an overcorrection in some areas that seems to result from consistent but subtle differences in composition of specific rock types. By expanding the model to include an additional factor reflecting the presence of a major tectonic unit, the Rohrbach block, the overcorrection is removed. This iterative process simultaneously refines both the geochemical map by removing extraneous variation and the geological map by suggesting a more detailed classification of rock types. ?? 1995 International Association for Mathematical Geology.

  17. A joint latent class analysis for adjusting survival bias with application to a trauma transfusion study

    PubMed Central

    Ning, Jing; Rahbar, Mohammad H.; Choi, Sangbum; Hong, Chuan; Piao, Jin; del Junco, Deborah J.; Fox, Erin E.; Rahbar, Elaheh; Holcomb, John B.

    2015-01-01

    There is no clear classification rule to rapidly identify trauma patients who are severely hemorrhaging and may need substantial blood transfusions. Massive transfusion (MT), defined as the transfusion of at least 10 units of red blood cells within 24 h of hospital admission, has served as a conventional surrogate that has been used to develop early predictive algorithms and establish criteria for ordering an MT protocol from the blood bank. However, the conventional MT rule is a poor proxy, because it is likely to misclassify many severely hemorrhaging trauma patients as they could die before receiving the 10th red blood cells transfusion. In this article, we propose to use a latent class model to obtain a more accurate and complete metric in the presence of early death. Our new approach incorporates baseline patient information from the time of hospital admission, by combining respective models for survival time and usage of blood products transfused within the framework of latent class analysis. To account for statistical challenges, caused by induced dependent censoring inherent in 24-h sums of transfusions, we propose to estimate an improved standard via a pseudo-likelihood function using an expectation-maximization algorithm with the inverse weighting principle. We evaluated the performance of our new standard in simulation studies and compared with the conventional MT definition using actual patient data from the Prospective Observational Multicenter Major Trauma Transfusion study. PMID:26256455

  18. A joint latent class analysis for adjusting survival bias with application to a trauma transfusion study.

    PubMed

    Ning, Jing; Rahbar, Mohammad H; Choi, Sangbum; Hong, Chuan; Piao, Jin; del Junco, Deborah J; Fox, Erin E; Rahbar, Elaheh; Holcomb, John B

    2016-01-15

    There is no clear classification rule to rapidly identify trauma patients who are severely hemorrhaging and may need substantial blood transfusions. Massive transfusion (MT), defined as the transfusion of at least 10 units of red blood cells within 24 h of hospital admission, has served as a conventional surrogate that has been used to develop early predictive algorithms and establish criteria for ordering an MT protocol from the blood bank. However, the conventional MT rule is a poor proxy, because it is likely to misclassify many severely hemorrhaging trauma patients as they could die before receiving the 10th red blood cells transfusion. In this article, we propose to use a latent class model to obtain a more accurate and complete metric in the presence of early death. Our new approach incorporates baseline patient information from the time of hospital admission, by combining respective models for survival time and usage of blood products transfused within the framework of latent class analysis. To account for statistical challenges, caused by induced dependent censoring inherent in 24-h sums of transfusions, we propose to estimate an improved standard via a pseudo-likelihood function using an expectation-maximization algorithm with the inverse weighting principle. We evaluated the performance of our new standard in simulation studies and compared with the conventional MT definition using actual patient data from the Prospective Observational Multicenter Major Trauma Transfusion study. Copyright © 2015 John Wiley & Sons, Ltd.

  19. A probabilistic analysis reveals fundamental limitations with the environmental impact quotient and similar systems for rating pesticide risks

    PubMed Central

    Schleier, Jerome J.

    2014-01-01

    Comparing risks among pesticides has substantial utility for decision makers. However, if rating schemes to compare risks are to be used, they must be conceptually and mathematically sound. We address limitations with pesticide risk rating schemes by examining in particular the Environmental Impact Quotient (EIQ) using, for the first time, a probabilistic analytic technique. To demonstrate the consequences of mapping discrete risk ratings to probabilities, adjusted EIQs were calculated for a group of 20 insecticides in four chemical classes. Using Monte Carlo simulation, adjusted EIQs were determined under different hypothetical scenarios by incorporating probability ranges. The analysis revealed that pesticides that have different EIQs, and therefore different putative environmental effects, actually may be no different when incorporating uncertainty. The EIQ equation cannot take into account uncertainty the way that it is structured and provide reliable quotients of pesticide impact. The EIQ also is inconsistent with the accepted notion of risk as a joint probability of toxicity and exposure. Therefore, our results suggest that the EIQ and other similar schemes be discontinued in favor of conceptually sound schemes to estimate risk that rely on proper integration of toxicity and exposure information. PMID:24795854

  20. 3D Indoor Building Environment Reconstruction using Least Square Adjustment, Polynomial Kernel, Interval Analysis and Homotopy Continuation

    NASA Astrophysics Data System (ADS)

    Jamali, Ali; Anton, François; Rahman, Alias Abdul; Mioc, Darka

    2016-10-01

    Nowadays, municipalities intend to have 3D city models for facility management, disaster management and architectural planning. Indoor models can be reconstructed from construction plans but sometimes, they are not available or very often, they differ from `as-built' plans. In this case, the buildings and their rooms must be surveyed. One of the most utilized methods of indoor surveying is laser scanning. The laser scanning method allows taking accurate and detailed measurements. However, Terrestrial Laser Scanner is costly and time consuming. In this paper, several techniques for indoor 3D building data acquisition have been investigated. For reducing the time and cost of indoor building data acquisition process, the Trimble LaserAce 1000 range finder is used. The proposed approache use relatively cheap equipment: a light Laser Rangefinder which appear to be feasible, but it needs to be tested to see if the observation accuracy is sufficient for the 3D building modelling. The accuracy of the rangefinder is evaluated and a simple spatial model is reconstructed from real data. This technique is rapid (it requires a shorter time as compared to others), but the results show inconsistencies in horizontal angles for short distances in indoor environments. The range finder horizontal angle sensor was calibrated using a least square adjustment algorithm, a polynomial kernel, interval analysis and homotopy continuation.

  1. Analysis of ultra-deep targeted sequencing reveals mutation burden is associated with gender and clinical outcome in lung adenocarcinoma

    PubMed Central

    Li, Fuqiang; Wu, Kui; Zhang, Xin; He, Jianxing

    2016-01-01

    Gender-associated difference in incidence and clinical outcomes of lung cancer have been established, but the biological mechanisms underlying these gender-associated differences are less studied. Recently we have characterized the genomic landscape of lung adenocarcinoma derived from Chinese population (Reference [1]). In this study we evaluated the clinical significance of mutation burden in lung adenocarcinoma and found that the male tumors harbored statistically greater burden of genetic alterations than female counterparts (Male median 3 (range 0–34) vs female median = 2 (0–24), male to female ratio = 1.636, 95% CI = 1.343–1.992) after adjustment of age at surgery, stage, smoking status. Kaplan-Meier survival analysis revealed that greater burden of genetic alterations was associated with worse overall survival. Moreover, multivariable analysis demonstrated mutation burden was an independent prognostic factor for the patients. Taken together, our analysis demonstrated gender disparity of mutation burden and their prognostic value in lung adenocarcinoma. This gender difference in mutation burden might provide an explanation for the distinct difference in the clinical outcomes between sexes in lung adenocarcinoma. PMID:27009843

  2. Adjustment of Adaptive Gain with Bounded Linear Stability Analysis to Improve Time-Delay Margin for Metrics-Driven Adaptive Control

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

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

  3. Design and error analysis of adjustable reflection-type magneto-optical photonic crystals for optical isolator application

    NASA Astrophysics Data System (ADS)

    Zamani, Mehdi; Ghanaatshoar, Majid

    2014-05-01

    We have performed a theoretical study on the case of reflection-type one-dimensional magnetophotonic crystals (MPCs) to establish a practical magneto-optical isolator (MOI). We have introduced thin MPC structures with concurrent high reflectance and large Kerr rotation for oblique incidence, and with the capability of being adjusted to perfect MOIs. It has been shown that the adjustment technique can also provide a framework for establishment of MPCs which are stable against fabrication and setup errors.

  4. Nonlinear relative-proportion-based route adjustment process for day-to-day traffic dynamics: modeling, equilibrium and stability analysis

    NASA Astrophysics Data System (ADS)

    Zhu, Wenlong; Ma, Shoufeng; Tian, Junfang; Li, Geng

    2016-11-01

    Travelers' route adjustment behaviors in a congested road traffic network are acknowledged as a dynamic game process between them. Existing Proportional-Switch Adjustment Process (PSAP) models have been extensively investigated to characterize travelers' route choice behaviors; PSAP has concise structure and intuitive behavior rule. Unfortunately most of which have some limitations, i.e., the flow over adjustment problem for the discrete PSAP model, the absolute cost differences route adjustment problem, etc. This paper proposes a relative-Proportion-based Route Adjustment Process (rePRAP) maintains the advantages of PSAP and overcomes these limitations. The rePRAP describes the situation that travelers on higher cost route switch to those with lower cost at the rate that is unilaterally depended on the relative cost differences between higher cost route and its alternatives. It is verified to be consistent with the principle of the rational behavior adjustment process. The equivalence among user equilibrium, stationary path flow pattern and stationary link flow pattern is established, which can be applied to judge whether a given network traffic flow has reached UE or not by detecting the stationary or non-stationary state of link flow pattern. The stability theorem is proved by the Lyapunov function approach. A simple example is tested to demonstrate the effectiveness of the rePRAP model.

  5. Arbuscular mycorrhizal symbiosis and osmotic adjustment in response to NaCl stress: a meta-analysis

    PubMed Central

    Augé, Robert M.; Toler, Heather D.; Saxton, Arnold M.

    2014-01-01

    Arbuscular mycorrhizal (AM) symbiosis can enhance plant resistance to NaCl stress in several ways. Two fundamental roles involve osmotic and ionic adjustment. By stimulating accumulation of solutes, the symbiosis can help plants sustain optimal water balance and diminish Na+ toxicity. The size of the AM effect on osmolytes has varied widely and is unpredictable. We conducted a meta-analysis to determine the size of the AM effect on 22 plant solute characteristics after exposure to NaCl and to examine how experimental conditions have influenced the AM effect. Viewed across studies, AM symbioses have had marked effects on plant K+, increasing root and shoot K+ concentrations by an average of 47 and 42%, respectively, and root and shoot K+/Na+ ratios by 47 and 58%, respectively. Among organic solutes, soluble carbohydrates have been most impacted, with AM-induced increases of 28 and 19% in shoots and roots. The symbiosis has had no consistent effect on several characteristics, including root glycine betaine concentration, root or shoot Cl− concentrations, leaf Ψπ, or shoot proline or polyamine concentrations. The AM effect has been very small for shoot Ca++ concentration and root concentrations of Na+, Mg++ and proline. Interpretations about AM-conferred benefits regarding these compounds may be best gauged within the context of the individual studies. Shoot and root K+/Na+ ratios and root proline concentration showed significant between-study heterogeneity, and we examined nine moderator variables to explore what might explain the differences in mycorrhizal effects on these parameters. Moderators with significant impacts included AM taxa, host type, presence or absence of AM growth promotion, stress severity, and whether NaCl constituted part or all of the experimental saline stress treatment. Meta-regression of shoot K+/Na+ ratio showed a positive response to root colonization, and root K+/Na+ ratio a negative response to time of exposure to NaCl. PMID:25368626

  6. A Cost-effectiveness Analysis of Laparoscopic Gastric Bypass, Adjustable Gastric Banding and Non-Surgical Weight Loss Interventions

    PubMed Central

    Salem, Leon; Devlin, Allison; Sullivan, Sean D.; Flum, David R.

    2009-01-01

    Setting Laparoscopic adjustable gastric banding (LAGB) and Laparoscopic Roux-en-Y gastric bypass (LRYGB) are the two most commonly performed bariatric procedures. While both procedures likely reduce healthcare expenditures related to the resolution of comorbid conditions, they have different rates of perioperative risks and differential rates of associated weight loss. Objective We designed a model to evaluate the incremental cost-effectiveness (ICER) of these procedures compared to non-operative weight loss interventions and to each other. Methods Deterministic, payer-perspective model comparing the lifetime expected costs and outcomes of LAGB, LRYGB and non-surgical treatment. The major endpoints were survival, health related quality of life and weight loss. Life expectancy and lifetime medical costs were calculated across age, sex and body mass index (BMI) strata using previously published data. Results For both men and women LRYGB and LAGB were cost-effective at less than $25,000/QALY even when evaluating the full range of baseline BMI and estimates of adverse outcomes, weight loss and costs. For base-case scenarios in men (age 35, BMI 40) the ICER was $11,604 per QALY for LAGB, compared to $18,543 per QALY for LRYGB. For base-case scenarios in women (age 35, BMI 40) the ICER was $8,878 per QALY for LAGB, compared to $14,680 per QALY for LRYGB. Conclusions Modeled cost-effectiveness analysis showed that both operative interventions for morbid obesity, LAGB and RYGB, were cost-effective at less than $25,000, and LAGB was more cost-effective than RYGB for all the base-case scenarios. PMID:18069075

  7. Principal-component-based population structure adjustment in the North American Rheumatoid Arthritis Consortium data: impact of single-nucleotide polymorphism set and analysis method

    PubMed Central

    2009-01-01

    Population structure occurs when a sample is composed of individuals with different ancestries and can result in excess type I error in genome-wide association studies. Genome-wide principal-component analysis (PCA) has become a popular method for identifying and adjusting for subtle population structure in association studies. Using the Genetic Analysis Workshop 16 (GAW16) NARAC data, we explore two unresolved issues concerning the use of genome-wide PCA to account for population structure in genetic associations studies: the choice of single-nucleotide polymorphism (SNP) subset and the choice of adjustment model. We computed PCs for subsets of genome-wide SNPs with varying levels of LD. The first two PCs were similar for all subsets and the first three PCs were associated with case status for all subsets. When the PCs associated with case status were included as covariates in an association model, the reduction in genomic inflation factor was similar for all SNP sets. Several models have been proposed to account for structure using PCs, but it is not yet clear whether the different methods will result in substantively different results for association studies with individuals of European descent. We compared genome-wide association p-values and results for two positive-control SNPs previously associated with rheumatoid arthritis using four PC adjustment methods as well as no adjustment and genomic control. We found that in this sample, adjusting for the continuous PCs or adjusting for discrete clusters identified using the PCs adequately accounts for the case-control population structure, but that a recently proposed randomization test performs poorly. PMID:20017972

  8. The Impact of Financial Sophistication on Adjustable Rate Mortgage Ownership

    ERIC Educational Resources Information Center

    Smith, Hyrum; Finke, Michael S.; Huston, Sandra J.

    2011-01-01

    The influence of a financial sophistication scale on adjustable-rate mortgage (ARM) borrowing is explored. Descriptive statistics and regression analysis using recent data from the Survey of Consumer Finances reveal that ARM borrowing is driven by both the least and most financially sophisticated households but for different reasons. Less…

  9. Using team cognitive work analysis to reveal healthcare team interactions in a birthing unit

    PubMed Central

    Ashoori, Maryam; Burns, Catherine M.; d'Entremont, Barbara; Momtahan, Kathryn

    2014-01-01

    Cognitive work analysis (CWA) as an analytical approach for examining complex sociotechnical systems has shown success in modelling the work of single operators. The CWA approach incorporates social and team interactions, but a more explicit analysis of team aspects can reveal more information for systems design. In this paper, Team CWA is explored to understand teamwork within a birthing unit at a hospital. Team CWA models are derived from theories and models of teamworkand leverage the existing CWA approaches to analyse team interactions. Team CWA is explained and contrasted with prior approaches to CWA. Team CWA does not replace CWA, but supplements traditional CWA to more easily reveal team information. As a result, Team CWA may be a useful approach to enhance CWA in complex environments where effective teamwork is required. Practitioner Summary: This paper looks at ways of analysing cognitive work in healthcare teams. Team Cognitive Work Analysis, when used to supplement traditional Cognitive Work Analysis, revealed more team information than traditional Cognitive Work Analysis. Team Cognitive Work Analysis should be considered when studying teams PMID:24837514

  10. Analysis of ISO NE Balancing Requirements: Uncertainty-based Secure Ranges for ISO New England Dynamic Inerchange Adjustments

    SciTech Connect

    Etingov, Pavel V.; Makarov, Yuri V.; Wu, Di; Hou, Zhangshuan; Sun, Yannan; Maslennikov, S.; Luo, X.; Zheng, T.; George, S.; Knowland, T.; Litvinov, E.; Weaver, S.; Sanchez, E.

    2013-01-31

    The document describes detailed uncertainty quantification (UQ) methodology developed by PNNL to estimate secure ranges of potential dynamic intra-hour interchange adjustments in the ISO-NE system and provides description of the dynamic interchange adjustment (DINA) tool developed under the same contract. The overall system ramping up and down capability, spinning reserve requirements, interchange schedules, load variations and uncertainties from various sources that are relevant to the ISO-NE system are incorporated into the methodology and the tool. The DINA tool has been tested by PNNL and ISO-NE staff engineers using ISO-NE data.

  11. Development and Validation of a Brief Version of the Dyadic Adjustment Scale With a Nonparametric Item Analysis Model

    ERIC Educational Resources Information Center

    Sabourin, Stephane; Valois, Pierre; Lussier, Yvan

    2005-01-01

    The main purpose of the current research was to develop an abbreviated form of the Dyadic Adjustment Scale (DAS) with nonparametric item response theory. The authors conducted 5 studies, with a total participation of 8,256 married or cohabiting individuals. Results showed that the item characteristic curves behaved in a monotonically increasing…

  12. Proteomic and genomic analysis reveals novel Campylobacter jejuni outer membrane proteins and potential heterogeneity.

    PubMed

    Watson, Eleanor; Sherry, Aileen; Inglis, Neil F; Lainson, Alex; Jyothi, Dushyanth; Yaga, Raja; Manson, Erin; Imrie, Lisa; Everest, Paul; Smith, David G E

    2014-09-01

    Gram-negative bacterial outer membrane proteins play important roles in the interaction of bacteria with their environment including nutrient acquisition, adhesion and invasion, and antibiotic resistance. In this study we identified 47 proteins within the Sarkosyl-insoluble fraction of Campylobacter jejuni 81-176, using LC-ESI-MS/MS. Comparative analysis of outer membrane protein sequences was visualised to reveal protein distribution within a panel of Campylobacter spp., identifying several C. jejuni-specific proteins. Smith-Waterman analyses of C. jejuni homologues revealed high sequence conservation amongst a number of hypothetical proteins, sequence heterogeneity of other proteins and several proteins which are absent in a proportion of strains.

  13. Meta-Analysis of Gene Expression Profiles in Acute Promyelocytic Leukemia Reveals Involved Pathways

    PubMed Central

    Jalili, Mahdi; Salehzadeh-Yazdi, Ali; Mohammadi, Saeed; Yaghmaie, Marjan; Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran

    2017-01-01

    Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis. Results: Our analysis revealed a gene signature with 406 genes that are up or down-regulated in APL. The pathway analysis determined that MAPK pathway and its involved elements such as JUN gene and AP-1 play important roles in APL pathogenesis along with insulin-like growth factor–binding protein-7. Conclusion: The results of this meta-analysis could be useful for developing more effective therapy strategies and new targets for diagnosis and drugs. PMID:28286608

  14. The original and simplified Wells rules and age-adjusted D-dimer testing to rule out pulmonary embolism: an individual patient data meta-analysis.

    PubMed

    van Es, N; Kraaijpoel, N; Klok, F A; Huisman, M V; Den Exter, P L; Mos, I C M; Galipienzo, J; Büller, H R; Bossuyt, P M

    2017-04-01

    Essentials Evidence for the simplified Wells rule in ruling out acute pulmonary embolism (PE) is scarce. This was a post-hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The simplified Wells rule combined with age-adjusted D-dimer testing may safely rule out PE. Given its ease of use, the simplified Wells rule is to be preferred over the original Wells rule.

  15. Reciprocal influences between maternal parenting and child adjustment in a high-risk population: a 5-year cross-lagged analysis of bidirectional effects.

    PubMed

    Barbot, Baptiste; Crossman, Elizabeth; Hunter, Scott R; Grigorenko, Elena L; Luthar, Suniya S

    2014-09-01

    This study examines longitudinally the bidirectional influences between maternal parenting (behaviors and parenting stress) and mothers' perceptions of their children's adjustment, in a multivariate approach. Data was gathered from 361 low-income mothers (many with psychiatric diagnoses) reporting on their parenting behavior, parenting stress, and their child's adjustment, in a 2-wave longitudinal study over 5 years. Measurement models were developed to derive 4 broad parenting constructs (involvement, control, rejection, and stress) and 3 child adjustment constructs (internalizing problems, externalizing problems, and social competence). After measurement invariance of these constructs was confirmed across relevant groups and over time, both measurement models were integrated in a single crossed-lagged regression analysis of latent constructs. Multiple reciprocal influences were observed between parenting and perceived child adjustment over time: Externalizing and internalizing problems in children were predicted by baseline maternal parenting behaviors, and child social competence was found to reduce parental stress and increase parental involvement and appropriate monitoring. These findings on the motherhood experience are discussed in light of recent research efforts to understand mother-child bidirectional influences and their potential for practical applications.

  16. Reciprocal Influences Between Maternal Parenting and Child Adjustment in a High-risk Population: A Five-Year Cross-Lagged Analysis of Bidirectional Effects

    PubMed Central

    Barbot, Baptiste; Crossman, Elizabeth; Hunter, Scott R.; Grigorenko, Elena L.; Luthar, Suniya S.

    2014-01-01

    This study examines longitudinally the bidirectional influences between maternal parenting (behaviors and parenting stress) and mothers' perceptions of their children's adjustment, in a multivariate approach. Data was gathered from 361 low-income mothers (many with psychiatric diagnoses) reporting on their parenting behavior, parenting stress and their child's adjustment, in a two-wave longitudinal study over 5 years. Measurement models were developed to derive four broad parenting constructs (Involvement, Control, Rejection, and Stress) and three child adjustment constructs (Internalizing problems, Externalizing problems, and Social competence). After measurement invariance of these constructs was confirmed across relevant groups and over time, both measurement models were integrated in a single crossed-lagged regression analysis of latent constructs. Multiple reciprocal influence were observed between parenting and perceived child adjustment over time: Externalizing and internalizing problems in children were predicted by baseline maternal parenting behaviors, while child social competence was found to reduce parental stress and increase parental involvement and appropriate monitoring. These findings on the motherhood experience are discussed in light of recent research efforts to understand mother-child bi-directional influences, and their potential for practical applications. PMID:25089759

  17. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells.

    PubMed

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-03-29

    The 'neural plate border' of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure.

  18. Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    PubMed Central

    2013-01-01

    Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 103 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed. Importantly, cellulases of some GH families are present in fungi that are not known to have cellulose-degrading ability. In addition, our results also showed that in general, plant pathogenic fungi have the highest number of CAZymes. Biotrophic fungi tend to have fewer CAZymes than necrotrophic and hemibiotrophic fungi. Pathogens of dicots often contain more pectinases than fungi infecting monocots. Interestingly, besides yeasts, many saprophytic fungi that are highly active in degrading plant biomass contain fewer CAZymes than plant pathogenic fungi. Furthermore, analysis of the gene expression profile of the wheat scab fungus Fusarium graminearum revealed that most of the CAZyme genes related to cell wall degradation were up-regulated during plant infection. Phylogenetic analysis also

  19. Rotating Snakes Illusion—Quantitative Analysis Reveals a Region in Luminance Space With Opposite Illusory Rotation

    PubMed Central

    Atala-Gérard, Lea

    2017-01-01

    The Rotating Snakes Illusion employs patterns with repetitive asymmetric luminance steps forming a “snake wheel.” In the underlying luminance sequence {black, dark grey, white, light grey}, coded as {0, g1, 100, g2}, we varied g1 and g2 and measured illusion strength via nulling: Saccades were performed next to a “snake wheel” that rotated physically; observers adjusted rotation until a stationary percept obtained. Observers performed the perceptual nulling of the seeming rotation reliably. Typical settings for (g1, g2), measured from images by Kitaoka, are around (20%, 60%). Indeed, we found a marked illusion in the region (g1≈{0%–25%}, g2≈{20%–75%}) with a rotation speed of ≈1°/s. Surprisingly, we detected a second “island” around (70%, 95%) with opposite direction of the illusory rotation and weaker illusion. Our quantitative measurements of illusion strength confirmed the optimal luminance choices of the standard snake wheel and, unexpectedly, revealed an opposite rotation illusion. PMID:28228928

  20. Rotating Snakes Illusion-Quantitative Analysis Reveals a Region in Luminance Space With Opposite Illusory Rotation.

    PubMed

    Atala-Gérard, Lea; Bach, Michael

    2017-01-01

    The Rotating Snakes Illusion employs patterns with repetitive asymmetric luminance steps forming a "snake wheel." In the underlying luminance sequence {black, dark grey, white, light grey}, coded as {0, g1, 100, g2}, we varied g1 and g2 and measured illusion strength via nulling: Saccades were performed next to a "snake wheel" that rotated physically; observers adjusted rotation until a stationary percept obtained. Observers performed the perceptual nulling of the seeming rotation reliably. Typical settings for (g1, g2), measured from images by Kitaoka, are around (20%, 60%). Indeed, we found a marked illusion in the region (g1≈{0%-25%}, g2≈{20%-75%}) with a rotation speed of ≈1°/s. Surprisingly, we detected a second "island" around (70%, 95%) with opposite direction of the illusory rotation and weaker illusion. Our quantitative measurements of illusion strength confirmed the optimal luminance choices of the standard snake wheel and, unexpectedly, revealed an opposite rotation illusion.

  1. Individual account retirement plans: an analysis of the 2007 survey of consumer finances, with market adjustments to June 2009.

    PubMed

    Copeland, Craig

    2009-08-01

    LATEST SCF DATA: This Issue Brief assesses the current status of Americans' savings for retirement by examining the incidence of individual account plans among families, as well as the average amount of assets accumulated in these accounts. The 2007 Survey of Consumer Finances (SCF), the Federal Reserve Board's triennial survey of wealth, is the basis for this study, as it is a leading source of data on Americans' wealth, provides detailed information on retirement plan incidence and account balances among families, and is the latest available. ACCOUNTING FOR THE ECONOMIC DOWNTURN: While 2007 SCF is the most comprehensive and current survey of Americans' finances, its timing was unfortunate due to the significant downturn in the economy in 2008 just after the survey was released. To account for that change, this analysis provides estimates of the changes in asset values from the end of 2007 to mid-June 2009 for individual account plan balances. The account balances of the defined contribution plans and IRAs are adjusted based on the asset allocation reported within the plans by using equity market returns and bond market returns from January 1, 2008, to June 19, 2009. MEDIAN ASSET LEVELS FOR DEFINED CONTRIBUTION PLANS: Among all families with a defined contribution plan in 2007, the median (mid-point) plan balance was $31,800, up 16 percent from 2004. According to EBRI estimates, this dropped 16.4 percent (to $26,578) from year-end 2007 to mid-June 2009. Losses were higher for families with more than $100,000 a year in income (down 22 percent) or having a net worth in the top 10 percent (down 28 percent). MEDIAN ASSET LEVELS FOR IRA/KEOGH PLANS: Among all families with an IRA/Keogh plan, the median value of their plan was $34,000 in 2007, up 3 percent from 2004. EBRI estimates this median value dropped 15 percent (to $28,955) from year-end 2007 to mid-June 2009. LESS THAN HALF OF ALL FAMILIES HAVE A RETIREMENT PLAN THROUGH A CURRENT JOB: In 2007, 40.6 percent of

  2. Reticulate evolutionary history and extensive introgression in mosquito species revealed by phylogenetic network analysis.

    PubMed

    Wen, Dingqiao; Yu, Yun; Hahn, Matthew W; Nakhleh, Luay

    2016-06-01

    The role of hybridization and subsequent introgression has been demonstrated in an increasing number of species. Recently, Fontaine et al. (Science, 347, 2015, 1258524) conducted a phylogenomic analysis of six members of the Anopheles gambiae species complex. Their analysis revealed a reticulate evolutionary history and pointed to extensive introgression on all four autosomal arms. The study further highlighted the complex evolutionary signals that the co-occurrence of incomplete lineage sorting (ILS) and introgression can give rise to in phylogenomic analyses. While tree-based methodologies were used in the study, phylogenetic networks provide a more natural model to capture reticulate evolutionary histories. In this work, we reanalyse the Anopheles data using a recently devised framework that combines the multispecies coalescent with phylogenetic networks. This framework allows us to capture ILS and introgression simultaneously, and forms the basis for statistical methods for inferring reticulate evolutionary histories. The new analysis reveals a phylogenetic network with multiple hybridization events, some of which differ from those reported in the original study. To elucidate the extent and patterns of introgression across the genome, we devise a new method that quantifies the use of reticulation branches in the phylogenetic network by each genomic region. Applying the method to the mosquito data set reveals the evolutionary history of all the chromosomes. This study highlights the utility of 'network thinking' and the new insights it can uncover, in particular in phylogenomic analyses of large data sets with extensive gene tree incongruence.

  3. Proteomics Analysis of Ovarian Cancer Cell Lines and Tissues Reveals Drug Resistance-associated Proteins

    PubMed Central

    CRUZ*, ISA N.; COLEY*, HELEN M.; KRAMER, HOLGER B.; MADHURI, THUMULURU KAVITAH; SAFUWAN, NUR A.M.; ANGELINO, ANA RITA; YANG, MIN

    2016-01-01

    Background: Carboplatin and paclitaxel form the cornerstone of chemotherapy for epithelial ovarian cancer, however, drug resistance to these agents continues to present challenges. Despite extensive research, the mechanisms underlying this resistance remain unclear. Materials and Methods: A 2D-gel proteomics method was used to analyze protein expression levels of three human ovarian cancer cell lines and five biopsy samples. Representative proteins identified were validated via western immunoblotting. Ingenuity pathway analysis revealed metabolomic pathway changes. Results: A total of 189 proteins were identified with restricted criteria. Combined treatment targeting the proteasome-ubiquitin pathway resulted in re-sensitisation of drug-resistant cells. In addition, examination of five surgical biopsies of ovarian tissues revealed α-enolase (ENOA), elongation factor Tu, mitochondrial (EFTU), glyceraldehyde-3-phosphate dehydrogenase (G3P), stress-70 protein, mitochondrial (GRP75), apolipoprotein A-1 (APOA1), peroxiredoxin (PRDX2) and annexin A (ANXA) as candidate biomarkers of drug-resistant disease. Conclusion: Proteomics combined with pathway analysis provided information for an effective combined treatment approach overcoming drug resistance. Analysis of cell lines and tissues revealed potential prognostic biomarkers for ovarian cancer. *These Authors contributed equally to this study. PMID:28031236

  4. Ancestry analysis reveals a predominant Native American component with moderate European admixture in Bolivians.

    PubMed

    Heinz, Tanja; Alvarez-Iglesias, Vanesa; Pardo-Seco, Jacobo; Taboada-Echalar, Patricia; Gómez-Carballa, Alberto; Torres-Balanza, Antonio; Rocabado, Omar; Carracedo, Angel; Vullo, Carlos; Salas, Antonio

    2013-09-01

    We have genotyped 46 Ancestry Informative Markers (AIMs) in two of the most populated areas in Bolivia, namely, La Paz (Andean region; n=105), and Chuquisaca (Sub-Andean region; n=73). Using different analytical tools, we inferred admixture proportions of these two American communities by comparing the genetic profiles with those publicly available from the CEPH (Centre d'Etude du Polymorphisme Humain) panel representing three main continental groups (Africa, Europe, and America). By way of simulations, we first evaluated the minimum sample size needed in order to obtain accurate estimates of ancestry proportions. The results indicated that sample sizes above 30 individuals could be large enough to estimate main continental ancestry proportions using the 46 AIMs panel. With the exception of a few individuals, the results also indicated that Bolivians showed a predominantly Native American ancestry with variable levels of European admixture. The proportions of ancestry were statistically different in La Paz and Chuquisaca: the Native American component was 86% and 77% (Mann-Whitney U-test: un-adjusted P-value=2.1×10(-5)), while the European ancestry was 13% and 21% (Mann-Whitney U-test: un-adjusted P-value=3.6×10(-5)), respectively. The African ancestry in Bolivians captured by the AIMs analyzed in the present study was below 2%. The inferred ancestry of Bolivians fits well with previous studies undertaken on haplotype data, indicating a major proportion of Native American lineages. The genetic differences observed in these two groups suggest that forensic genetic analysis should be better performed based on local databases built in the main Bolivian areas.

  5. Increasing shape modelling accuracy by adjusting for subject positioning: an application to the analysis of radiographic proximal femur symmetry using data from the Osteoarthritis Initiative.

    PubMed

    Lindner, C; Wallis, G A; Cootes, T F

    2014-04-01

    In total hip arthroplasty, the shape of the contra-lateral femur frequently serves as a template for preoperative planning. Previous research on contra-lateral femoral symmetry has been based on conventional hip geometric measurements (which reduce shape to a series of linear measurements) and did not take the effect of subject positioning on radiographic femur shape into account. The aim of this study was to analyse proximal femur symmetry based on statistical shape models (SSMs) which quantify global femoral shape while also adjusting for differences in subject positioning during image acquisition. We applied our recently developed fully automatic shape model matching (FASMM) system to automatically segment the proximal femur from AP pelvic radiographs to generate SSMs of the proximal femurs of 1258 Caucasian females (mean age: 61.3 SD=9.0). We used a combined SSM (capturing the left and right femurs) to identify and adjust for shape variation attributable to subject positioning as well as a single SSM (including all femurs as left femurs) to analyse proximal femur symmetry. We also calculated conventional hip geometric measurements (head diameter, neck width, shaft width and neck-shaft angle) using the output of the FASMM system. The combined SSM revealed two modes that were clearly attributable to subject positioning. The average difference (mean point-to-curve distance) between left and right femur shape was 1.0mm before and 0.8mm after adjusting for these two modes. The automatic calculation of conventional hip geometric measurements after adjustment gave an average absolute percent asymmetry of within 3.1% and an average absolute difference of within 1.1mm or 2.9° for all measurements. We conclude that (i) for Caucasian females the global shape of the right and left proximal femurs is symmetric without isolated locations of asymmetry; (ii) a combined left-right SSM can be used to adjust for radiographic shape variation due to subject positioning; and (iii

  6. Meta-GWAS and Meta-Analysis of Exome Array Studies Do Not Reveal Genetic Determinants of Serum Hepcidin

    PubMed Central

    Galesloot, Tessel E.; van Dijk, Freerk; Geurts-Moespot, Anneke J.; Girelli, Domenico; Kiemeney, Lambertus A. L. M.; Sweep, Fred C. G. J.; Swertz, Morris A.; van der Meer, Peter; Camaschella, Clara; Toniolo, Daniela; Vermeulen, Sita H.; van der Harst, Pim; Swinkels, Dorine W.

    2016-01-01

    Serum hepcidin concentration is regulated by iron status, inflammation, erythropoiesis and numerous other factors, but underlying processes are incompletely understood. We studied the association of common and rare single nucleotide variants (SNVs) with serum hepcidin in one Italian study and two large Dutch population-based studies. We genotyped common SNVs with genome-wide association study (GWAS) arrays and subsequently performed imputation using the 1000 Genomes reference panel. Cohort-specific GWAS were performed for log-transformed serum hepcidin, adjusted for age and gender, and results were combined in a fixed-effects meta-analysis (total N 6,096). Six top SNVs (p<5x10-6) were genotyped in 3,821 additional samples, but associations were not replicated. Furthermore, we meta-analyzed cohort-specific exome array association results of rare SNVs with serum hepcidin that were available for two of the three cohorts (total N 3,226), but no exome-wide significant signal (p<1.4x10-6) was identified. Gene-based meta-analyses revealed 19 genes that showed significant association with hepcidin. Our results suggest the absence of common SNVs and rare exonic SNVs explaining a large proportion of phenotypic variation in serum hepcidin. We recommend extension of our study once additional substantial cohorts with hepcidin measurements, GWAS and/or exome array data become available in order to increase power to identify variants that explain a smaller proportion of hepcidin variation. In addition, we encourage follow-up of the potentially interesting genes that resulted from the gene-based analysis of low-frequency and rare variants. PMID:27846281

  7. Dietary intake and plasma metabolomic analysis of polyunsaturated fatty acids in bipolar subjects reveal dysregulation of linoleic acid metabolism.

    PubMed

    Evans, Simon J; Ringrose, Rachel N; Harrington, Gloria J; Mancuso, Peter; Burant, Charles F; McInnis, Melvin G

    2014-10-01

    Polyunsaturated fatty acids (PUFA) profiles associate with risk for mood disorders. This poses the hypothesis of metabolic differences between patients and unaffected healthy controls that relate to the primary illness or are secondary to medication use or dietary intake. However, dietary manipulation or supplementation studies show equivocal results improving mental health outcomes. This study investigates dietary patterns and metabolic profiles relevant to PUFA metabolism, in bipolar I individuals compared to non-psychiatric controls. We collected seven-day diet records and performed metabolomic analysis of fasted plasma collected immediately after diet recording. Regression analyses adjusted for age, gender and energy intake found that bipolar individuals had significantly lower intake of selenium and PUFAs, including eicosapentaenoic acid (EPA) (n-3), docosahexaenoic acid (DHA) (n-3), arachidonic acid (AA) (n-6) and docosapentaenoic acid (DPA) (n-3/n-6 mix); and significantly increased intake of the saturated fats, eicosanoic and docosanoic acid. Regression analysis of metabolomic data derived from plasma samples, correcting for age, gender, BMI, psychiatric medication use and dietary PUFA intake, revealed that bipolar individuals had reduced 13S-HpODE, a major peroxidation product of the n-6, linoleic acid (LA), reduced eicosadienoic acid (EDA), an elongation product of LA; reduced prostaglandins G2, F2 alpha and E1, synthesized from n-6 PUFA; and reduced EPA. These observations remained significant or near significant after Bonferroni correction and are consistent with metabolic variances between bipolar and control individuals with regard to PUFA metabolism. These findings suggest that specific dietary interventions aimed towards correcting these metabolic disparities may impact health outcomes for individuals with bipolar disorder.

  8. Using a detailed uncertainty analysis to adjust mapped rates of forest disturbance derived from Landsat time series data (Invited)

    NASA Astrophysics Data System (ADS)

    Cohen, W. B.; Yang, Z.; Stehman, S.; Huang, C.; Healey, S. P.

    2013-12-01

    Forest ecosystem process models require spatially and temporally detailed disturbance data to accurately predict fluxes of carbon or changes in biodiversity over time. A variety of new mapping algorithms using dense Landsat time series show great promise for providing disturbance characterizations at an annual time step. These algorithms provide unprecedented detail with respect to timing, magnitude, and duration of individual disturbance events, and causal agent. But all maps have error and disturbance maps in particular can have significant omission error because many disturbances are relatively subtle. Because disturbance, although ubiquitous, can be a relatively rare event spatially in any given year, omission errors can have a great impact on mapped rates. Using a high quality reference disturbance dataset, it is possible to not only characterize map errors but also to adjust mapped disturbance rates to provide unbiased rate estimates with confidence intervals. We present results from a national-level disturbance mapping project (the North American Forest Dynamics project) based on the Vegetation Change Tracker (VCT) with annual Landsat time series and uncertainty analyses that consist of three basic components: response design, statistical design, and analyses. The response design describes the reference data collection, in terms of the tool used (TimeSync), a formal description of interpretations, and the approach for data collection. The statistical design defines the selection of plot samples to be interpreted, whether stratification is used, and the sample size. Analyses involve derivation of standard agreement matrices between the map and the reference data, and use of inclusion probabilities and post-stratification to adjust mapped disturbance rates. Because for NAFD we use annual time series, both mapped and adjusted rates are provided at an annual time step from ~1985-present. Preliminary evaluations indicate that VCT captures most of the higher

  9. End-point parameter adjustment on a small desk-top programmable calculator for logit-log analysis of radioimmunoassay data.

    PubMed

    Hatch, K F; Coles, E; Busey, H; Goldman, S C

    1976-08-01

    We describe an improved method of logit-log curve fitting, by adjusting end-point parameters in radioimmunoassay studies, for use with a small desk-top programmable calculator. Straight logit-log analyses are often deficient because of their high sensitivity to small errors in the end-point parametes B0 and NSB (the actual measured activity in the tubes). The literature suggests techniques for adjusting these end-point parameters, but they require too much computing time and programming space to be used with a desk-top programmable calculator. The extension to the logit-log model presented here is easily handled by the programmable calculator and provides a good estimate of the change required in B0 and NSB to obtain a better fit. The program requires 1.5 min to run on our desk-top programmable calculator, and has resulted in improved data analysis for all of the 11 types of radioimmunoassay studied.

  10. Wavelet-based regularity analysis reveals Recurrent Spatiotemporal Behavior in Resting-state fMRI

    PubMed Central

    Smith, Robert X.; Jann, Kay; Ances, Beau; Wang, Danny J.J.

    2015-01-01

    One of the major findings from multi-modal neuroimaging studies in the past decade is that the human brain is anatomically and functionally organized into large-scale networks. In resting state fMRI (rs-fMRI), spatial patterns emerge when temporal correlations between various brain regions are tallied, evidencing networks of ongoing intercortical cooperation. However, the dynamic structure governing the brain’s spontaneous activity is far less understood due to the short and noisy nature of the rs-fMRI signal. Here we develop a wavelet-based regularity analysis based on noise estimation capabilities of the wavelet transform to measure recurrent temporal pattern stability within the rs-fMRI signal across multiple temporal scales. The method consists of performing a stationary wavelet transform (SWT) to preserve signal structure, followed by construction of “lagged” subsequences to adjust for correlated features, and finally the calculation of sample entropy across wavelet scales based on an “objective” estimate of noise level at each scale. We found that the brain’s default mode network (DMN) areas manifest a higher level of irregularity in rs-fMRI time series than rest of the brain. In 25 aged subjects with mild cognitive impairment and 25 matched healthy controls, wavelet based regularity analysis showed improved sensitivity in detecting changes in the regularity of rs-fMRI signals between the two groups within the DMN and executive control networks, compared to standard multiscale entropy analysis. Wavelet based regularity analysis based on noise estimation capabilities of the wavelet transform is a promising technique to characterize the dynamic structure of rs-fMRI as well as other biological signals. PMID:26096080

  11. New molecular phenotypes in the dst mutants of Arabidopsis revealed by DNA microarray analysis.

    PubMed

    Pérez-Amador, M A; Lidder, P; Johnson, M A; Landgraf, J; Wisman, E; Green, P J

    2001-12-01

    In this study, DNA microarray analysis was used to expand our understanding of the dst1 mutant of Arabidopsis. The dst (downstream) mutants were isolated originally as specifically increasing the steady state level and the half-life of DST-containing transcripts. As such, txhey offer a unique opportunity to study rapid sequence-specific mRNA decay pathways in eukaryotes. These mutants show a threefold to fourfold increase in mRNA abundance for two transgenes and an endogenous gene, all containing DST elements, when examined by RNA gel blot analysis; however, they show no visible aberrant phenotype. Here, we use DNA microarrays to identify genes with altered expression levels in dst1 compared with the parental plants. In addition to verifying the increase in the transgene mRNA levels, which were used to isolate these mutants, we were able to identify new genes with altered mRNA abundance in dst1. RNA gel blot analysis confirmed the microarray data for all genes tested and also was used to catalog the first molecular differences in gene expression between the dst1 and dst2 mutants. These differences revealed previously unknown molecular phenotypes for the dst mutants that will be helpful in future analyses. Cluster analysis of genes altered in dst1 revealed new coexpression patterns that prompt new hypotheses regarding the nature of the dst1 mutation and a possible role of the DST-mediated mRNA decay pathway in plants.

  12. Proteomic analysis reveals diverse proline hydroxylation-mediated oxygen-sensing cellular pathways in cancer cells

    PubMed Central

    Liu, Bing; Gao, Yankun; Ruan, Hai-Bin; Chen, Yue

    2016-01-01

    Proline hydroxylation is a critical cellular mechanism regulating oxygen-response pathways in tumor initiation and progression. Yet, its substrate diversity and functions remain largely unknown. Here, we report a system-wide analysis to characterize proline hydroxylation substrates in cancer cells using an immunoaffinity-purification assisted proteomics strategy. We identified 562 sites from 272 proteins in HeLa cells. Bioinformatic analysis revealed that proline hydroxylation substrates are significantly enriched with mRNA processing and stress-response cellular pathways with canonical and diverse flanking sequence motifs. Structural analysis indicates a significant enrichment of proline hydroxylation participating in the secondary structure of substrate proteins. Our study identified and validated Brd4, a key transcription factor, as a novel proline hydroxylation substrate. Functional analysis showed that the inhibition of proline hydroxylation pathway significantly reduced the proline hydroxylation abundance on Brd4 and affected Brd4-mediated transcriptional activity as well as cell proliferation in AML leukemia cells. Taken together, our study identified a broad regulatory role of proline hydroxylation in cellular oxygen-sensing pathways and revealed potentially new targets that dynamically respond to hypoxia microenvironment in tumor cells. PMID:27764789

  13. Asymmetric Genome Organization in an RNA Virus Revealed via Graph-Theoretical Analysis of Tomographic Data

    PubMed Central

    Geraets, James A.; Dykeman, Eric C.; Stockley, Peter G.; Ranson, Neil A.; Twarock, Reidun

    2015-01-01

    Cryo-electron microscopy permits 3-D structures of viral pathogens to be determined in remarkable detail. In particular, the protein containers encapsulating viral genomes have been determined to high resolution using symmetry averaging techniques that exploit the icosahedral architecture seen in many viruses. By contrast, structure determination of asymmetric components remains a challenge, and novel analysis methods are required to reveal such features and characterize their functional roles during infection. Motivated by the important, cooperative roles of viral genomes in the assembly of single-stranded RNA viruses, we have developed a new analysis method that reveals the asymmetric structural organization of viral genomes in proximity to the capsid in such viruses. The method uses geometric constraints on genome organization, formulated based on knowledge of icosahedrally-averaged reconstructions and the roles of the RNA-capsid protein contacts, to analyse cryo-electron tomographic data. We apply this method to the low-resolution tomographic data of a model virus and infer the unique asymmetric organization of its genome in contact with the protein shell of the capsid. This opens unprecedented opportunities to analyse viral genomes, revealing conserved structural features and mechanisms that can be targeted in antiviral drug design. PMID:25793998

  14. Local coexistence of VO2 phases revealed by deep data analysis

    SciTech Connect

    Strelcov, Evgheni; Ievlev, Anton; Tselev, Alexander; Kolmakov, Andrei; Kalinin, Sergei V.

    2016-07-07

    We report a synergistic approach of micro-Raman spectroscopic mapping and deep data analysis to study the distribution of crystallographic phases and ferroelastic domains in a defected Al-doped VO2 microcrystal. Bayesian linear unmixing revealed an uneven distribution of the T phase, which is stabilized by the surface defects and uneven local doping that went undetectable by other classical analysis techniques such as PCA and SIMPLISMA. This work demonstrates the impact of information recovery via statistical analysis and full mapping in spectroscopic studies of vanadium dioxide systems, which is commonly substituted by averaging or single point-probing approaches, both of which suffer from information misinterpretation due to low resolving power.

  15. Local coexistence of VO2 phases revealed by deep data analysis

    PubMed Central

    Strelcov, Evgheni; Ievlev, Anton; Belianinov, Alex; Tselev, Alexander; Kolmakov, Andrei; Kalinin, Sergei V.

    2016-01-01

    We report a synergistic approach of micro-Raman spectroscopic mapping and deep data analysis to study the distribution of crystallographic phases and ferroelastic domains in a defected Al-doped VO2 microcrystal. Bayesian linear unmixing revealed an uneven distribution of the T phase, which is stabilized by the surface defects and uneven local doping that went undetectable by other classical analysis techniques such as PCA and SIMPLISMA. This work demonstrates the impact of information recovery via statistical analysis and full mapping in spectroscopic studies of vanadium dioxide systems, which is commonly substituted by averaging or single point-probing approaches, both of which suffer from information misinterpretation due to low resolving power. PMID:27384473

  16. Local coexistence of VO2 phases revealed by deep data analysis

    DOE PAGES

    Strelcov, Evgheni; Ievlev, Anton; Tselev, Alexander; ...

    2016-07-07

    We report a synergistic approach of micro-Raman spectroscopic mapping and deep data analysis to study the distribution of crystallographic phases and ferroelastic domains in a defected Al-doped VO2 microcrystal. Bayesian linear unmixing revealed an uneven distribution of the T phase, which is stabilized by the surface defects and uneven local doping that went undetectable by other classical analysis techniques such as PCA and SIMPLISMA. This work demonstrates the impact of information recovery via statistical analysis and full mapping in spectroscopic studies of vanadium dioxide systems, which is commonly substituted by averaging or single point-probing approaches, both of which suffer frommore » information misinterpretation due to low resolving power.« less

  17. Revealing the association between cerebrovascular accidents and ambient temperature: a meta-analysis

    NASA Astrophysics Data System (ADS)

    Zorrilla-Vaca, Andrés; Healy, Ryan Jacob; Silva-Medina, Melissa M.

    2016-10-01

    The association between cerebrovascular accidents (CVA) and weather has been described across several studies showing multiple conflicting results. In this paper, we aim to conduct a meta-analysis to further clarify this association, as well as to find the potential sources of heterogeneity. PubMed, EMBASE, and Google Scholar were searched from inception through 2015, for articles analyzing the correlation between the incidence of CVA and temperature. A pooled effect size (ES) was estimated using random effects model and expressed as absolute values. Subgroup analyses by type of CVA were also performed. Heterogeneity and influence of covariates—including geographic latitude of the study site, male percentage, average temperature, and time interval—were assessed by meta-regression analysis. Twenty-six articles underwent full data extraction and scoring. A total of 19,736 subjects with CVA from 12 different countries were included and grouped as ischemic strokes (IS; n = 14,199), intracerebral hemorrhages (ICH; n = 3798), and subarachnoid hemorrhages (SAH; n = 1739). Lower ambient temperature was significantly associated with increase in incidence of overall CVA when using unadjusted (pooled ES = 0.23, P < 0.001) and adjusted data (pooled ES = 0.03, P = 0.003). Subgroup analyses showed that lower temperature has higher impact on the incidence of ICH (pooled ES = 0.34, P < 0.001), than that of IS (pooled ES = 0.22, P < 0.001) and SAH (pooled ES = 0.11, P = 0.012). In meta-regression analysis, the geographic latitude of the study site was the most influencing factor on this association (Z-score = 8.68). Synthesis of the existing data provides evidence supporting that a lower ambient temperature increases the incidence of CVA. Further population-based studies conducted at negative latitudes are needed to clarify the influence of this factor.

  18. Multilocus Sequence Analysis of Nectar Pseudomonads Reveals High Genetic Diversity and Contrasting Recombination Patterns

    PubMed Central

    Álvarez-Pérez, Sergio; de Vega, Clara; Herrera, Carlos M.

    2013-01-01

    The genetic and evolutionary relationships among floral nectar-dwelling Pseudomonas ‘sensu stricto’ isolates associated to South African and Mediterranean plants were investigated by multilocus sequence analysis (MLSA) of four core housekeeping genes (rrs, gyrB, rpoB and rpoD). A total of 35 different sequence types were found for the 38 nectar bacterial isolates characterised. Phylogenetic analyses resulted in the identification of three main clades [nectar groups (NGs) 1, 2 and 3] of nectar pseudomonads, which were closely related to five intrageneric groups: Pseudomonas oryzihabitans (NG 1); P. fluorescens, P. lutea and P. syringae (NG 2); and P. rhizosphaerae (NG 3). Linkage disequilibrium analysis pointed to a mostly clonal population structure, even when the analysis was restricted to isolates from the same floristic region or belonging to the same NG. Nevertheless, signatures of recombination were observed for NG 3, which exclusively included isolates retrieved from the floral nectar of insect-pollinated Mediterranean plants. In contrast, the other two NGs comprised both South African and Mediterranean isolates. Analyses relating diversification to floristic region and pollinator type revealed that there has been more unique evolution of the nectar pseudomonads within the Mediterranean region than would be expected by chance. This is the first work analysing the sequence of multiple loci to reveal geno- and ecotypes of nectar bacteria. PMID:24116076

  19. Analysis of hydrocarbon-contaminated groundwater metagenomes as revealed by high-throughput sequencing.

    PubMed

    Abbai, Nathlee S; Pillay, Balakrishna

    2013-07-01

    The tendency for chlorinated aliphatics and aromatic hydrocarbons to accumulate in environments such as groundwater and sediments poses a serious environmental threat. In this study, the metabolic capacity of hydrocarbon (aromatics and chlorinated aliphatics)-contaminated groundwater in the KwaZulu-Natal province of South Africa has been elucidated for the first time by analysis of pyrosequencing data. The taxonomic data revealed that the metagenomes were dominated by the phylum Proteobacteria (mainly Betaproteobacteria). In addition, Flavobacteriales, Sphingobacteria, Burkholderiales, and Rhodocyclales were the predominant orders present in the individual metagenomes. These orders included microorganisms (Flavobacteria, Dechloromonas aromatica RCB, and Azoarcus) involved in the degradation of aromatic compounds and various other hydrocarbons that were present in the groundwater. Although the metabolic reconstruction of the metagenome represented composite cell networks, the information obtained was sufficient to address questions regarding the metabolic potential of the microbial communities and to correlate the data to the contamination profile of the groundwater. Genes involved in the degradation of benzene and benzoate, heavy metal-resistance mechanisms appeared to provide a survival strategy used by the microbial communities. Analysis of the pyrosequencing-derived data revealed that the metagenomes represent complex microbial communities that have adapted to the geochemical conditions of the groundwater as evidenced by the presence of key enzymes/genes conferring resistance to specific contaminants. Thus, pyrosequencing analysis of the metagenomes provided insights into the microbial activities in hydrocarbon-contaminated habitats.

  20. Adjustment of Measurements with Multiplicative Errors: Error Analysis, Estimates of the Variance of Unit Weight, and Effect on Volume Estimation from LiDAR-Type Digital Elevation Models

    PubMed Central

    Shi, Yun; Xu, Peiliang; Peng, Junhuan; Shi, Chuang; Liu, Jingnan

    2014-01-01

    Modern observation technology has verified that measurement errors can be proportional to the true values of measurements such as GPS, VLBI baselines and LiDAR. Observational models of this type are called multiplicative error models. This paper is to extend the work of Xu and Shimada published in 2000 on multiplicative error models to analytical error analysis of quantities of practical interest and estimates of the variance of unit weight. We analytically derive the variance-covariance matrices of the three least squares (LS) adjustments, the adjusted measurements and the corrections of measurements in multiplicative error models. For quality evaluation, we construct five estimators for the variance of unit weight in association of the three LS adjustment methods. Although LiDAR measurements are contaminated with multiplicative random errors, LiDAR-based digital elevation models (DEM) have been constructed as if they were of additive random errors. We will simulate a model landslide, which is assumed to be surveyed with LiDAR, and investigate the effect of LiDAR-type multiplicative error measurements on DEM construction and its effect on the estimate of landslide mass volume from the constructed DEM. PMID:24434880

  1. Adjustment of measurements with multiplicative errors: error analysis, estimates of the variance of unit weight, and effect on volume estimation from LiDAR-type digital elevation models.

    PubMed

    Shi, Yun; Xu, Peiliang; Peng, Junhuan; Shi, Chuang; Liu, Jingnan

    2014-01-10

    Modern observation technology has verified that measurement errors can be proportional to the true values of measurements such as GPS, VLBI baselines and LiDAR. Observational models of this type are called multiplicative error models. This paper is to extend the work of Xu and Shimada published in 2000 on multiplicative error models to analytical error analysis of quantities of practical interest and estimates of the variance of unit weight. We analytically derive the variance-covariance matrices of the three least squares (LS) adjustments, the adjusted measurements and the corrections of measurements in multiplicative error models. For quality evaluation, we construct five estimators for the variance of unit weight in association of the three LS adjustment methods. Although LiDAR measurements are contaminated with multiplicative random errors, LiDAR-based digital elevation models (DEM) have been constructed as if they were of additive random errors. We will simulate a model landslide, which is assumed to be surveyed with LiDAR, and investigate the effect of LiDAR-type multiplicative error measurements on DEM construction and its effect on the estimate of landslide mass volume from the constructed DEM.

  2. The relationship between periodic dinucleotides and the nucleosomal DNA deformation revealed by normal mode analysis

    NASA Astrophysics Data System (ADS)

    Wang, Debby D.; Yan, Hong

    2011-12-01

    Nucleosomes, which contain DNA and proteins, are the basic unit of eukaryotic chromatins. Polymers such as DNA and proteins are dynamic, and their conformational changes can lead to functional changes. Periodic dinucleotide patterns exist in nucleosomal DNA chains and play an important role in the nucleosome structure. In this paper, we use normal mode analysis to detect significant structural deformations of nucleosomal DNA and investigate the relationship between periodic dinucleotides and DNA motions. We have found that periodic dinucleotides are usually located at the peaks or valleys of DNA and protein motions, revealing that they dominate the nucleosome dynamics. Also, a specific dinucleotide pattern CA/TG appears most frequently.

  3. Correction: Comparative analysis of fungal genomes reveals different plant cell wall degrading capacity in fungi

    PubMed Central

    2014-01-01

    Abstract The version of this article published in BMC Genomics 2013, 14: 274, contains 9 unpublished genomes (Botryobasidium botryosum, Gymnopus luxurians, Hypholoma sublateritium, Jaapia argillacea, Hebeloma cylindrosporum, Conidiobolus coronatus, Laccaria amethystina, Paxillus involutus, and P. rubicundulus) downloaded from JGI website. In this correction, we removed these genomes after discussion with editors and data producers whom we should have contacted before downloading these genomes. Removing these data did not alter the principle results and conclusions of our original work. The relevant Figures 1, 2, 3, 4 and 6; and Table 1 have been revised. Additional files 1, 3, 4, and 5 were also revised. We would like to apologize for any confusion or inconvenience this may have caused. Background Fungi produce a variety of carbohydrate activity enzymes (CAZymes) for the degradation of plant polysaccharide materials to facilitate infection and/or gain nutrition. Identifying and comparing CAZymes from fungi with different nutritional modes or infection mechanisms may provide information for better understanding of their life styles and infection models. To date, over hundreds of fungal genomes are publicly available. However, a systematic comparative analysis of fungal CAZymes across the entire fungal kingdom has not been reported. Results In this study, we systemically identified glycoside hydrolases (GHs), polysaccharide lyases (PLs), carbohydrate esterases (CEs), and glycosyltransferases (GTs) as well as carbohydrate-binding modules (CBMs) in the predicted proteomes of 94 representative fungi from Ascomycota, Basidiomycota, Chytridiomycota, and Zygomycota. Comparative analysis of these CAZymes that play major roles in plant polysaccharide degradation revealed that fungi exhibit tremendous diversity in the number and variety of CAZymes. Among them, some families of GHs and CEs are the most prevalent CAZymes that are distributed in all of the fungi analyzed

  4. An analysis of the dynamic avalanche mechanism of an improved FCE diode with a deep p+ adjusting region

    NASA Astrophysics Data System (ADS)

    Cailin, Wang; Lei, Zhang

    2015-04-01

    An improved field charge extraction (FCE) diode with a deep p+ adjusting region at the cathode side is studied. The reverse recovery mechanism and electric field gradient are thoroughly analyzed and validated using ISE simulation results. The results show that, based on the premise of ensuring the static characteristics, the improved FCE diode can clearly improve the softness and effectively suppress the peak electric field of the nn- junction at the cathode side during reverse recovery, and thus has a high dynamic avalanche capability compared with conventional FCE diodes. Project supported by the Doctoral Program of Higher Education of China (RFDP) (No. 20136118110004), and the National Natural Science Foundation of China (Nos. 51077110, 51477137).

  5. Shortwave radiative forcing, rapid adjustment, and feedback to the surface by sulfate geoengineering: analysis of the Geoengineering Model Intercomparison Project G4 scenario

    NASA Astrophysics Data System (ADS)

    Kashimura, Hiroki; Abe, Manabu; Watanabe, Shingo; Sekiya, Takashi; Ji, Duoying; Moore, John C.; Cole, Jason N. S.; Kravitz, Ben

    2017-03-01

    This study evaluates the forcing, rapid adjustment, and feedback of net shortwave radiation at the surface in the G4 experiment of the Geoengineering Model Intercomparison Project by analysing outputs from six participating models. G4 involves injection of 5 Tg yr-1 of SO2, a sulfate aerosol precursor, into the lower stratosphere from year 2020 to 2069 against a background scenario of RCP4.5. A single-layer atmospheric model for shortwave radiative transfer is used to estimate the direct forcing of solar radiation management (SRM), and rapid adjustment and feedbacks from changes in the water vapour amount, cloud amount, and surface albedo (compared with RCP4.5). The analysis shows that the globally and temporally averaged SRM forcing ranges from -3.6 to -1.6 W m-2, depending on the model. The sum of the rapid adjustments and feedback effects due to changes in the water vapour and cloud amounts increase the downwelling shortwave radiation at the surface by approximately 0.4 to 1.5 W m-2 and hence weaken the effect of SRM by around 50 %. The surface albedo changes decrease the net shortwave radiation at the surface; it is locally strong (˜ -4 W m-2) in snow and sea ice melting regions, but minor for the global average. The analyses show that the results of the G4 experiment, which simulates sulfate geoengineering, include large inter-model variability both in the direct SRM forcing and the shortwave rapid adjustment from change in the cloud amount, and imply a high uncertainty in modelled processes of sulfate aerosols and clouds.

  6. Genetic factors in nonsmokers with age-related macular degeneration revealed through genome-wide gene-environment interaction analysis.

    PubMed

    Naj, Adam C; Scott, William K; Courtenay, Monique D; Cade, William H; Schwartz, Stephen G; Kovach, Jaclyn L; Agarwal, Anita; Wang, Gaofeng; Haines, Jonathan L; Pericak-Vance, Margaret A

    2013-05-01

    Relatively little is known about the interaction between genes and environment in the complex etiology of age-related macular degeneration (AMD). This study aimed to identify novel factors associated with AMD by analyzing gene-smoking interactions in a genome-wide association study of 1207 AMD cases and 686 controls of Caucasian background with genotype data on 668,238 single nucleotide polymorphisms (SNPs) after quality control. Participants' history of smoking at least 100 cigarettes lifetime was determined by a self-administered questionnaire. SNP associations modeled the effect of the minor allele additively on AMD using logistic regression, with adjustment for age, sex, and ever/never smoking. Joint effects of SNPs and smoking were examined comparing a null model containing only age, sex, and smoking against an extended model including genotypic and interaction terms. Genome-wide significant main effects were detected at three known AMD loci: CFH (P = 7.51×10(-30) ), ARMS2 (P = 1.94×10(-23) ), and RDBP/CFB/C2 (P = 4.37×10(-10) ), while joint effects analysis revealed three genomic regions with P < 10(-5) . Analyses stratified by smoking found genetic associations largely restricted to nonsmokers, with one notable exception: the chromosome 18q22.1 intergenic SNP rs17073641 (between SERPINB8 and CDH7), more strongly associated in nonsmokers (OR = 0.57, P = 2.73 × 10(-5) ), with an inverse association among smokers (OR = 1.42, P = 0.00228), suggesting that smoking modifies the effect of some genetic polymorphisms on AMD risk.

  7. A combined clinical phenotype and lipidomic analysis reveals the impact of chronic kidney disease on lipid metabolism.

    PubMed

    Chen, Hua; Chen, Lin; Liu, Dan; Chen, Dan-Qian; Vaziri, Nosratola D; Yu, Xiao-Yong; Zhang, Li; Su, Wei; Bai, Xu; Zhao, Ying-Yong

    2017-03-13

    Chronic kidney disease (CKD) results in significant dyslipidemia and profound changes in lipid and lipoprotein metabolism. The associated dyslipidemia, in turn, contributes to progression of CKD and its cardiovascular complications. To gain an in-depth insight into the disorders of lipid metabolism in advanced CKD, we applied UPLC-HDMS-based lipidomics to measure serum lipid metabolites in 180 patients with advanced CKD and 120 age-matched healthy controls. We found significant increases in the levels of total free fatty acids, glycerolipids and glycerophospholipids in patients with CKD. The levels of free fatty acids, glycerolipids and glycerophospholipids directly correlated with the level of serum triglyceride, and inversely correlated with the levels of total cholesterol and eGFR. A total of 126 lipid species were identified from positive and negative ion modes. 113 out of 126 identified lipid species were significantly altered in patients with CKD based on the adjusted FDR method. These results point to profound disturbance of fatty acid and triglyceride metabolisms in patients with CKD. Logistic regression analysis showed strong correlations between serum methyl hexadecanoic acid, LPC(24:1), 3-oxooctadecanoic acid and PC(20:2/24:1) levels with eGFR and serum creatinine levels (R>0.8758). In conclusion application of UPLC-HDMS-based lipidomic technique revealed profound changes in lipid metabolites in patients with CKD. The observed increases in serum total fatty acids, glycerolipids and glycerophospholipids levels directly correlated with increased serum triglyceride level, and inversely correlated with the eGFR and triglyceride levels.

  8. Chromosome-specific segmentation revealed by structural analysis of individually isolated chromosomes.

    PubMed

    Kitada, Kunio; Taima, Akira; Ogasawara, Kiyomoto; Metsugi, Shouichi; Aikawa, Satoko

    2011-04-01

    Analysis of structural rearrangements at the individual chromosomal level is still technologically challenging. Here we optimized a chromosome isolation method using fluorescent marker-assisted laser-capture and laser-beam microdissection and applied it to structural analysis of two aberrant chromosomes found in a lung cancer cell line. A high-density array-comparative genomic hybridization (array-CGH) analysis of DNA samples prepared from each of the chromosomes revealed that these two chromosomes contained 296 and 263 segments, respectively, ranging from 1.5 kb to 784.3 kb in size, derived from different portions of chromosome 8. Among these segments, 242 were common in both aberrant chromosomes, but 75 were found to be chromosome-specific. Sequences of 263 junction sites connecting the ends of segments were determined using a PCR/Sanger-sequencing procedure. Overlapping microhomologies were found at 169 junction sites. Junction partners came from various portions of chromosome 8 and no biased pattern in the positional distribution of junction partners was detected. These structural characteristics suggested the occurrence of random fragmentation of the entire chromosome 8 followed by random rejoining of these fragments. Based on that, we proposed a model to explain how these aberrant chromosomes are formed. Through these structural analyses, it was demonstrated that the optimized chromosome isolation method described here can provide high-quality chromosomal DNA for high resolution array-CGH analysis and probably for massively parallel sequencing analysis.

  9. Phylogenomic Analysis of Oenococcus oeni Reveals Specific Domestication of Strains to Cider and Wines

    PubMed Central

    Campbell-Sills, Hugo; El Khoury, Mariette; Favier, Marion; Romano, Andrea; Biasioli, Franco; Spano, Giuseppe; Sherman, David J.; Bouchez, Olivier; Coton, Emmanuel; Coton, Monika; Okada, Sanae; Tanaka, Naoto; Dols-Lafargue, Marguerite; Lucas, Patrick M.

    2015-01-01

    Oenococcus oeni is a lactic acid bacteria species encountered particularly in wine, where it achieves the malolactic fermentation. Molecular typing methods have previously revealed that the species is made of several genetic groups of strains, some being specific to certain types of wines, ciders or regions. Here, we describe 36 recently released O. oeni genomes and the phylogenomic analysis of these 36 plus 14 previously reported genomes. We also report three genome sequences of the sister species Oenococcus kitaharae that were used for phylogenomic reconstructions. Phylogenomic and population structure analyses performed revealed that the 50 O. oeni genomes delineate two major groups of 12 and 37 strains, respectively, named A and B, plus a putative group C, consisting of a single strain. A study on the orthologs and single nucleotide polymorphism contents of the genetic groups revealed that the domestication of some strains to products such as cider, wine, or champagne, is reflected at the genetic level. While group A strains proved to be predominant in wine and to form subgroups adapted to specific types of wine such as champagne, group B strains were found in wine and cider. The strain from putative group C was isolated from cider and genetically closer to group B strains. The results suggest that ancestral O. oeni strains were adapted to low-ethanol containing environments such as overripe fruits, and that they were domesticated to cider and wine, with group A strains being naturally selected in a process of further domestication to specific wines such as champagne. PMID:25977455

  10. Spike-Triggered Covariance Analysis Reveals Phenomenological Diversity of Contrast Adaptation in the Retina

    PubMed Central

    Liu, Jian K.; Gollisch, Tim

    2015-01-01

    When visual contrast changes, retinal ganglion cells adapt by adjusting their sensitivity as well as their temporal filtering characteristics. The latter has classically been described by contrast-induced gain changes that depend on temporal frequency. Here, we explored a new perspective on contrast-induced changes in temporal filtering by using spike-triggered covariance analysis to extract multiple parallel temporal filters for individual ganglion cells. Based on multielectrode-array recordings from ganglion cells in the isolated salamander retina, we found that contrast adaptation of temporal filtering can largely be captured by contrast-invariant sets of filters with contrast-dependent weights. Moreover, differences among the ganglion cells in the filter sets and their contrast-dependent contributions allowed us to phenomenologically distinguish three types of filter changes. The first type is characterized by newly emerging features at higher contrast, which can be reproduced by computational models that contain response-triggered gain-control mechanisms. The second type follows from stronger adaptation in the Off pathway as compared to the On pathway in On-Off-type ganglion cells. Finally, we found that, in a subset of neurons, contrast-induced filter changes are governed by particularly strong spike-timing dynamics, in particular by pronounced stimulus-dependent latency shifts that can be observed in these cells. Together, our results show that the contrast dependence of temporal filtering in retinal ganglion cells has a multifaceted phenomenology and that a multi-filter analysis can provide a useful basis for capturing the underlying signal-processing dynamics. PMID:26230927

  11. Proteomic analysis of MG132-treated germinating pollen reveals expression signatures associated with proteasome inhibition.

    PubMed

    Vannini, Candida; Bracale, Marcella; Crinelli, Rita; Marconi, Valerio; Campomenosi, Paola; Marsoni, Milena; Scoccianti, Valeria

    2014-01-01

    Chemical inhibition of the proteasome has been previously found to effectively impair pollen germination and tube growth in vitro. However, the mediators of these effects at the molecular level are unknown. By performing 2DE proteomic analysis, 24 differentially expressed protein spots, representing 14 unique candidate proteins, were identified in the pollen of kiwifruit (Actinidia deliciosa) germinated in the presence of the MG132 proteasome inhibitor. qPCR analysis revealed that 11 of these proteins are not up-regulated at the mRNA level, but are most likely stabilized by proteasome inhibition. These differentially expressed proteins are predicted to function in various pathways including energy and lipid metabolism, cell wall synthesis, protein synthesis/degradation and stress responses. In line with this evidence, the MG132-induced changes in the proteome were accompanied by an increase in ATP and ROS content and by an alteration in fatty acid composition.

  12. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis

    NASA Astrophysics Data System (ADS)

    Kaminski, Naftali; Allard, John D.; Pittet, Jean F.; Zuo, Fengrong; Griffiths, Mark J. D.; Morris, David; Huang, Xiaozhu; Sheppard, Dean; Heller, Renu A.

    2000-02-01

    The molecular mechanisms of pulmonary fibrosis are poorly understood. We have used oligonucleotide arrays to analyze the gene expression programs that underlie pulmonary fibrosis in response to bleomycin, a drug that causes lung inflammation and fibrosis, in two strains of susceptible mice (129 and C57BL/6). We then compared the gene expression patterns in these mice with 129 mice carrying a null mutation in the epithelial-restricted integrin 6 subunit (6/-), which develop inflammation but are protected from pulmonary fibrosis. Cluster analysis identified two distinct groups of genes involved in the inflammatory and fibrotic responses. Analysis of gene expression at multiple time points after bleomycin administration revealed sequential induction of subsets of genes that characterize each response. The availability of this comprehensive data set should accelerate the development of more effective strategies for intervention at the various stages in the development of fibrotic diseases of the lungs and other organs.

  13. Analysis of miRNA market trends reveals hotspots of research activity.

    PubMed

    Oosta, Gary; Razvi, Enal

    2012-04-01

    We have conducted an analysis of the miRNA research marketplace by evaluating the publication trends in the field. In this article, we present the results of our analysis which reveals that hotspots exist in terms of research activities in the miRNA space--these hotspots illustrate the areas in the miRNA research space where specific miRNAs have been extensively studied, and other areas that represent new territory. We frame these data into the context of areas of opportunity for miRNA content harvest versus segments of opportunity for the development of research tools. Also presented in this article are the primary market data from online surveys we have performed with researchers involved in miRNA research around the world. Taken together, these data frame the current state of the miRNA marketplace and provide niches of opportunity for new entrants into this space.

  14. Co-occurrence correlations of heavy metals in sediments revealed using network analysis.

    PubMed

    Liu, Lili; Wang, Zhiping; Ju, Feng; Zhang, Tong

    2015-01-01

    In this study, the correlation-based study was used to identify the co-occurrence correlations among metals in marine sediment of Hong Kong, based on the long-term (from 1991 to 2011) temporal and spatial monitoring data. 14 stations out of the total 45 marine sediment monitoring stations were selected from three representative areas, including Deep Bay, Victoria Harbour and Mirs Bay. Firstly, Spearman's rank correlation-based network analysis was conducted as the first step to identify the co-occurrence correlations of metals from raw metadata, and then for further analysis using the normalized metadata. The correlations patterns obtained by network were consistent with those obtained by the other statistic normalization methods, including annual ratios, R-squared coefficient and Pearson correlation coefficient. Both Deep Bay and Victoria Harbour have been polluted by heavy metals, especially for Pb and Cu, which showed strong co-occurrence with other heavy metals (e.g. Cr, Ni, Zn and etc.) and little correlations with the reference parameters (Fe or Al). For Mirs Bay, which has better marine sediment quality compared with Deep Bay and Victoria Harbour, the co-occurrence patterns revealed by network analysis indicated that the metals in sediment dominantly followed the natural geography process. Besides the wide applications in biology, sociology and informatics, it is the first time to apply network analysis in the researches of environment pollutions. This study demonstrated its powerful application for revealing the co-occurrence correlations among heavy metals in marine sediments, which could be further applied for other pollutants in various environment systems.

  15. Dynamic transcriptional signature and cell fate analysis reveals plasticity of individual neural plate border cells

    PubMed Central

    Roellig, Daniela; Tan-Cabugao, Johanna; Esaian, Sevan; Bronner, Marianne E

    2017-01-01

    The ‘neural plate border’ of vertebrate embryos contains precursors of neural crest and placode cells, both defining vertebrate characteristics. How these lineages segregate from neural and epidermal fates has been a matter of debate. We address this by performing a fine-scale quantitative temporal analysis of transcription factor expression in the neural plate border of chick embryos. The results reveal significant overlap of transcription factors characteristic of multiple lineages in individual border cells from gastrula through neurula stages. Cell fate analysis using a Sox2 (neural) enhancer reveals that cells that are initially Sox2+ cells can contribute not only to neural tube but also to neural crest and epidermis. Moreover, modulating levels of Sox2 or Pax7 alters the apportionment of neural tube versus neural crest fates. Our results resolve a long-standing question and suggest that many individual border cells maintain ability to contribute to multiple ectodermal lineages until or beyond neural tube closure. DOI: http://dx.doi.org/10.7554/eLife.21620.001 PMID:28355135

  16. Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain.

    PubMed Central

    Bui, Q T; Zimmerman, J E; Liu, H; Bonini, N M

    2000-01-01

    The eyes absent (eya) gene is critical to eye formation in Drosophila; upon loss of eya function, eye progenitor cells die by programmed cell death. Moreover, ectopic eya expression directs eye formation, and eya functionally synergizes in vivo and physically interacts in vitro with two other genes of eye development, sine oculis and dachshund. The Eya protein sequence, while highly conserved to vertebrates, is novel. To define amino acids critical to the function of the Eya protein, we have sequenced eya alleles. These mutations have revealed that loss of the entire Eya Domain is null for eya activity, but that alleles with truncations within the Eya Domain display partial function. We then extended the molecular genetic analysis to interactions within the Eya Domain. This analysis has revealed regions of special importance to interaction with Sine Oculis or Dachshund. Select eya missense mutations within the Eya Domain diminished the interactions with Sine Oculis or Dachshund. Taken together, these data suggest that the conserved Eya Domain is critical for eya activity and may have functional subregions within it. PMID:10835393

  17. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain

    PubMed Central

    Jones, Christopher J.; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H.

    2016-01-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates. PMID:27297393

  18. Phenotypic Analysis Reveals that the 2010 Haiti Cholera Epidemic Is Linked to a Hypervirulent Strain.

    PubMed

    Satchell, Karla J F; Jones, Christopher J; Wong, Jennifer; Queen, Jessica; Agarwal, Shivani; Yildiz, Fitnat H

    2016-09-01

    Vibrio cholerae O1 El Tor strains have been responsible for pandemic cholera since 1961. These strains have evolved over time, spreading globally in three separate waves. Wave 3 is caused by altered El Tor (AET) variant strains, which include the strain with the signature ctxB7 allele that was introduced in 2010 into Haiti, where it caused a devastating epidemic. In this study, we used phenotypic analysis to compare an early isolate from the Haiti epidemic to wave 1 El Tor isolates commonly used for research. It is demonstrated that the Haiti isolate has increased production of cholera toxin (CT) and hemolysin, increased motility, and a reduced ability to form biofilms. This strain also outcompetes common wave 1 El Tor isolates for colonization of infant mice, indicating that it has increased virulence. Monitoring of CT production and motility in additional wave 3 isolates revealed that this phenotypic variation likely evolved over time rather than in a single genetic event. Analysis of available whole-genome sequences and phylogenetic analyses suggested that increased virulence arose from positive selection for mutations found in known and putative regulatory genes, including hns and vieA, diguanylate cyclase genes, and genes belonging to the lysR and gntR regulatory families. Overall, the studies presented here revealed that V. cholerae virulence potential can evolve and that the currently prevalent wave 3 AET strains are both phenotypically distinct from and more virulent than many El Tor isolates.

  19. Metabolic network analysis revealed distinct routes of deletion effects between essential and non-essential genes.

    PubMed

    Ma, Jing; Zhang, Xun; Ung, Choong Yong; Chen, Yu Zong; Li, Baowen

    2012-04-01

    Interest in essential genes has arisen recently given their importance in antimicrobial drug development. Although knockouts of essential genes are commonly known to cause lethal phenotypes, there is insufficient understanding on the intermediate changes followed by genetic perturbation and to what extent essential genes correlate to other genes. Here, we characterized the gene knockout effects by using a list of affected genes, termed as 'damage lists'. These damage lists were identified through a refined cascading failure approach that was based on a previous topological flux balance analysis. Using an Escherichia coli metabolic network, we incorporated essentiality information into damage lists and revealed that the knockout of an essential gene mainly affects a large range of other essential genes whereas knockout of a non-essential gene only interrupts other non-essential genes. Also, genes sharing common damage lists tend to have the same essentiality. We extracted 72 core functional modules from the common damage lists of essential genes and demonstrated their ability to halt essential metabolites production. Overall, our network analysis revealed that essential and non-essential genes propagated their deletion effects via distinct routes, conferring mechanistic explanation to the observed lethality phenotypes of essential genes.

  20. Molecular analysis of aggressive renal cell carcinoma with unclassified histology reveals distinct subsets

    PubMed Central

    Chen, Ying-Bei; Xu, Jianing; Skanderup, Anders Jacobsen; Dong, Yiyu; Brannon, A. Rose; Wang, Lu; Won, Helen H.; Wang, Patricia I.; Nanjangud, Gouri J.; Jungbluth, Achim A.; Li, Wei; Ojeda, Virginia; Hakimi, A. Ari; Voss, Martin H.; Schultz, Nikolaus; Motzer, Robert J.; Russo, Paul; Cheng, Emily H.; Giancotti, Filippo G.; Lee, William; Berger, Michael F.; Tickoo, Satish K.; Reuter, Victor E.; Hsieh, James J.

    2016-01-01

    Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%). Integrated analysis reveals a subset of 26% uRCC characterized by NF2 loss, dysregulated Hippo–YAP pathway and worse survival, whereas 21% uRCC with mutations of MTOR, TSC1, TSC2 or PTEN and hyperactive mTORC1 signalling are associated with better clinical outcome. FH deficiency (6%), chromatin/DNA damage regulator mutations (21%) and ALK translocation (2%) distinguish additional cases. Altogether, this study reveals distinct molecular subsets for 76% of our uRCC cohort, which could have diagnostic and therapeutic implications. PMID:27713405

  1. Transcriptome Analysis of Hamelia patens (Rubiaceae) Anthers Reveals Candidate Genes for Tapetum and Pollen Wall Development

    PubMed Central

    Yue, Lin; Twell, David; Kuang, Yanfeng; Liao, Jingping; Zhou, Xianqiang

    2017-01-01

    Studies of the anther transcriptome on non-model plants without a known genome are surprisingly scarce. RNA-Seq and digital gene expression (DGE) profiling provides a comprehensive approach to identify candidate genes contributing to developmental processes in non-model species. Here we built a transcriptome library of developing anthers of Hamelia patens and analyzed DGE profiles from each stage to identify genes that regulate tapetum and pollen development. In total 7,720 putative differentially expressed genes across four anther stages were identified. The number of putative stage-specific genes was: 776 at microspore mother cell stage, 807 at tetrad stage, 322 at uninucleate microspore stage, and the highest number (1,864) at bicellular pollen stage. GO enrichment analysis revealed 243 differentially expressed and 108 stage-specific genes that are potentially related to tapetum development, sporopollenin synthesis, and pollen wall. The number of expressed genes, their function and expression profiles were all significantly correlated with anther developmental processes. Overall comparisons of anther and pollen transcriptomes with those of rice and Arabidopsis together with the expression profiles of homologs of known anther-expressed genes, revealed conserved patterns and also divergence. The divergence may reflect taxon-specific differences in gene expression, the use RNA-seq as a more sensitive methodology, variation in tissue composition and sampling strategies. Given the lack of genomic sequence, this study succeeded in assigning putative identity to a significant proportion of anther-expressed genes and genes relevant to tapetum and pollen development in H. patens. The anther transcriptome revealed a molecular distinction between developmental stages, serving as a resource to unravel the functions of genes involved in anther development in H. patens and informing the analysis of other members of the Rubiaceae. PMID:28119704

  2. Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.

    PubMed

    Burney, Richard O; Talbi, Said; Hamilton, Amy E; Vo, Kim Chi; Nyegaard, Mette; Nezhat, Camran R; Lessey, Bruce A; Giudice, Linda C

    2007-08-01

    The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone-regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.

  3. RNA-Seq Analysis Reveals MAPKKK Family Members Related to Drought Tolerance in Maize

    PubMed Central

    Ren, Wen; Yang, Fengling; He, Hang; Zhao, Jiuran

    2015-01-01

    The mitogen-activated protein kinase (MAPK) cascade is an evolutionarily conserved signal transduction pathway that is involved in plant development and stress responses. As the first component of this phosphorelay cascade, mitogen-activated protein kinase kinase kinases (MAPKKKs) act as adaptors linking upstream signaling steps to the core MAPK cascade to promote the appropriate cellular responses; however, the functions of MAPKKKs in maize are unclear. Here, we identified 71 MAPKKK genes, of which 14 were novel, based on a computational analysis of the maize (Zea mays L.) genome. Using an RNA-seq analysis in the leaf, stem and root of maize under well-watered and drought-stress conditions, we identified 5,866 differentially expressed genes (DEGs), including 8 MAPKKK genes responsive to drought stress. Many of the DEGs were enriched in processes such as drought stress, abiotic stimulus, oxidation-reduction, and metabolic processes. The other way round, DEGs involved in processes such as oxidation, photosynthesis, and starch, proline, ethylene, and salicylic acid metabolism were clearly co-expressed with the MAPKKK genes. Furthermore, a quantitative real-time PCR (qRT-PCR) analysis was performed to assess the relative expression levels of MAPKKKs. Correlation analysis revealed that there was a significant correlation between expression levels of two MAPKKKs and relative biomass responsive to drought in 8 inbred lines. Our results indicate that MAPKKKs may have important regulatory functions in drought tolerance in maize. PMID:26599013

  4. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India.

    PubMed

    Gautam, Vikas; Patil, Prashant P; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B

    2016-10-21

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005-2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient's isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen.

  5. Multilocus sequence analysis reveals high genetic diversity in clinical isolates of Burkholderia cepacia complex from India

    PubMed Central

    Gautam, Vikas; Patil, Prashant P.; Kumar, Sunil; Midha, Samriti; Kaur, Mandeep; Kaur, Satinder; Singh, Meenu; Mali, Swapna; Shastri, Jayanthi; Arora, Anita; Ray, Pallab; Patil, Prabhu B.

    2016-01-01

    Burkholderia cepacia complex (Bcc) is a complex group of bacteria causing opportunistic infections in immunocompromised and cystic fibrosis (CF) patients. Herein, we report multilocus sequence typing and analysis of the 57 clinical isolates of Bcc collected over the period of seven years (2005–2012) from several hospitals across India. A total of 21 sequence types (ST) including two STs from cystic fibrosis patient’s isolates and twelve novel STs were identified in the population reflecting the extent of genetic diversity. Multilocus sequence analysis revealed two lineages in population, a major lineage belonging to B. cenocepacia and a minor lineage belonging to B. cepacia. Split-decomposition analysis suggests absence of interspecies recombination and intraspecies recombination contributed in generating genotypic diversity amongst isolates. Further linkage disequilibrium analysis indicates that recombination takes place at a low frequency, which is not sufficient to break down the clonal relationship. This knowledge of the genetic structure of Bcc population from a rapidly developing country will be invaluable in the epidemiology, surveillance and understanding global diversity of this group of a pathogen. PMID:27767197

  6. Cerebral Degeneration in Amyotrophic Lateral Sclerosis Revealed by 3-Dimensional Texture Analysis

    PubMed Central

    Maani, Rouzbeh; Yang, Yee-Hong; Emery, Derek; Kalra, Sanjay

    2016-01-01

    Introduction: Routine MR images do not consistently reveal pathological changes in the brain in ALS. Texture analysis, a method to quantitate voxel intensities and their patterns and interrelationships, can detect changes in images not apparent to the naked eye. Our objective was to evaluate cerebral degeneration in ALS using 3-dimensional texture analysis of MR images of the brain. Methods: In a case-control design, voxel-based texture analysis was performed on T1-weighted MR images of 20 healthy subjects and 19 patients with ALS. Four texture features, namely, autocorrelation, sum of squares variance, sum average, and sum variance were computed. Texture features were compared between the groups by statistical parametric mapping and correlated with clinical measures of disability and upper motor neuron dysfunction. Results: Texture features were different in ALS in motor regions including the precentral gyrus and corticospinal tracts. To a lesser extent, changes were also found in the thalamus, cingulate gyrus, and temporal lobe. Texture features in the precentral gyrus correlated with disease duration, and in the corticospinal tract they correlated with finger tapping speed. Conclusions: Changes in MR image textures are present in motor and non-motor regions in ALS and correlate with clinical features. Whole brain texture analysis has potential in providing biomarkers of cerebral degeneration in ALS. PMID:27064416

  7. Pretreatment and integrated analysis of spectral data reveal seaweed similarities based on chemical diversity.

    PubMed

    Wei, Feifei; Ito, Kengo; Sakata, Kenji; Date, Yasuhiro; Kikuchi, Jun

    2015-03-03

    Extracting useful information from high dimensionality and large data sets is a major challenge for data-driven approaches. The present study was aimed at developing novel integrated analytical strategies for comprehensively characterizing seaweed similarities based on chemical diversity. The chemical compositions of 107 seaweed and 2 seagrass samples were analyzed using multiple techniques, including Fourier transform infrared (FT-IR) and solid- and solution-state nuclear magnetic resonance (NMR) spectroscopy, thermogravimetry-differential thermal analysis (TG-DTA), inductively coupled plasma-optical emission spectrometry (ICP-OES), CHNS/O total elemental analysis, and isotope ratio mass spectrometry (IR-MS). The spectral data were preprocessed using non-negative matrix factorization (NMF) and NMF combined with multivariate curve resolution-alternating least-squares (MCR-ALS) methods in order to separate individual component information from the overlapping and/or broad spectral peaks. Integrated analysis of the preprocessed chemical data demonstrated distinct discrimination of differential seaweed species. Further network analysis revealed a close correlation between the heavy metal elements and characteristic components of brown algae, such as cellulose, alginic acid, and sulfated mucopolysaccharides, providing a componential basis for its metal-sorbing potential. These results suggest that this integrated analytical strategy is useful for extracting and identifying the chemical characteristics of diverse seaweeds based on large chemical data sets, particularly complicated overlapping spectral data.

  8. Whole population cell analysis of a landmark-rich mammalian epithelium reveals multiple elongation mechanisms

    PubMed Central

    Economou, Andrew D.; Brock, Lara J.; Cobourne, Martyn T.; Green, Jeremy B. A.

    2013-01-01

    Tissue elongation is a fundamental component of developing and regenerating systems. Although localised proliferation is an important mechanism for tissue elongation, potentially important contributions of other elongation mechanisms, specifically cell shape change, orientated cell division and cell rearrangement, are rarely considered or quantified, particularly in mammalian systems. Their quantification, together with proliferation, provides a rigorous framework for the analysis of elongation. The mammalian palatal epithelium is a landmark-rich tissue, marked by regularly spaced ridges (rugae), making it an excellent model in which to analyse the contributions of cellular processes to directional tissue growth. We captured confocal stacks of entire fixed mouse palate epithelia throughout the mid-gestation growth period, labelled with membrane, nuclear and cell proliferation markers and segmented all cells (up to ∼20,000 per palate), allowing the quantification of cell shape and proliferation. Using the rugae as landmarks, these measures revealed that the so-called growth zone is a region of proliferation that is intermittently elevated at ruga initiation. The distribution of oriented cell division suggests that it is not a driver of tissue elongation, whereas cell shape analysis revealed that both elongation of cells leaving the growth zone and apico-basal cell rearrangements do contribute significantly to directional growth. Quantitative comparison of elongation processes indicated that proliferation contributes most to elongation at the growth zone, but cell shape change and rearrangement contribute as much as 40% of total elongation. We have demonstrated the utility of an approach to analysing the cellular mechanisms underlying tissue elongation in mammalian tissues. It should be broadly applied to higher-resolution analysis of links between genotypes and malformation phenotypes. PMID:24173805

  9. Single-cell analysis reveals lineage segregation in early post-implantation mouse embryos.

    PubMed

    Wen, Jing; Zeng, Yanwu; Fang, Zhuoqing; Gu, Junjie; Ge, Laixiang; Tang, Fan; Qu, Zepeng; Hu, Jing; Cui, Yaru; Zhang, Kunshan; Wang, Junbang; Li, Siguang; Sun, Yi; Jin, Ying

    2017-03-15

    The mammalian post-implantation embryo has been extensively investigated at the tissue level. However, to unravel the molecular basis for the cell-fate plasticity and determination, it is essential to study the characteristics of individual cells. Especially, the individual definitive endoderm (DE) cells have not been characterized in vivo. Here, we report gene expression patterns in single cells freshly isolated from mouse embryos on days 5.5 and 6.5. Initial transcriptome data from 124 single cells yielded signature genes for the epiblast, visceral endoderm, and extra-embryonic ectoderm and revealed a unique distribution pattern of fibroblast growth factor (Fgf) ligands and receptors. Further analysis indicated that early-stage epiblast cells do not segregate into lineages of the major germ layers. Instead, some cells began to diverge from epiblast cells, displaying molecular features of the pre-mesendoderm by expressing higher levels of mesendoderm markers and lower levels of Sox3 transcripts. Analysis of single-cell high-throughput quantitative RT-PCR data from 441 cells identified a late stage of the day 6.5 embryo in which mesoderm and DE cells emerge, with many of them coexpressing Oct4 and Gata6. Analysis of single-cell RNA-seq data from 112 cells of the late-stage day 6.5 embryos revealed differentially expressed signaling genes and networks of transcription factors that might underlie the segregation of the mesoderm and DE lineages. Moreover, we discovered a subpopulation of mesoderm cells that possess molecular features of the extraembryonic mesoderm. This study provides fundamental insight into the molecular basis for lineage segregation in post-implantation mouse embryos.

  10. Genome-wide enrichment analysis between endometriosis and obesity-related traits reveals novel susceptibility loci

    PubMed Central

    Rahmioglu, Nilufer; Macgregor, Stuart; Drong, Alexander W.; Hedman, Åsa K.; Harris, Holly R.; Randall, Joshua C.; Prokopenko, Inga; Nyholt, Dale R.; Morris, Andrew P.; Montgomery, Grant W.; Missmer, Stacey A.; Lindgren, Cecilia M.; Zondervan, Krina T.

    2015-01-01

    Endometriosis is a chronic inflammatory condition in women that results in pelvic pain and subfertility, and has been associated with decreased body mass index (BMI). Genetic variants contributing to the heritable component have started to emerge from genome-wide association studies (GWAS), although the majority remain unknown. Unexpectedly, we observed an intergenic locus on 7p15.2 that was genome-wide significantly associated with both endometriosis and fat distribution (waist-to-hip ratio adjusted for BMI; WHRadjBMI) in an independent meta-GWAS of European ancestry individuals. This led us to investigate the potential overlap in genetic variants underlying the aetiology of endometriosis, WHRadjBMI and BMI using GWAS data. Our analyses demonstrated significant enrichment of common variants between fat distribution and endometriosis (P = 3.7 × 10−3), which was stronger when we restricted the investigation to more severe (Stage B) cases (P = 4.5 × 10−4). However, no genetic enrichment was observed between endometriosis and BMI (P = 0.79). In addition to 7p15.2, we identify four more variants with statistically significant evidence of involvement in both endometriosis and WHRadjBMI (in/near KIFAP3, CAB39L, WNT4, GRB14); two of these, KIFAP3 and CAB39L, are novel associations for both traits. KIFAP3, WNT4 and 7p15.2 are associated with the WNT signalling pathway; formal pathway analysis confirmed a statistically significant (P = 6.41 × 10−4) overrepresentation of shared associations in developmental processes/WNT signalling between the two traits. Our results demonstrate an example of potential biological pleiotropy that was hitherto unknown, and represent an opportunity for functional follow-up of loci and further cross-phenotype comparisons to assess how fat distribution and endometriosis pathogenesis research fields can inform each other. PMID:25296917

  11. Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia.

    PubMed

    Damaraju, E; Allen, E A; Belger, A; Ford, J M; McEwen, S; Mathalon, D H; Mueller, B A; Pearlson, G D; Potkin, S G; Preda, A; Turner, J A; Vaidya, J G; van Erp, T G; Calhoun, V D

    2014-01-01

    Schizophrenia is a psychotic disorder characterized by functional dysconnectivity or abnormal integration between distant brain regions. Recent functional imaging studies have implicated large-scale thalamo-cortical connectivity as being disrupted in patients. However, observed connectivity differences in schizophrenia have been inconsistent between studies, with reports of hyperconnectivity and hypoconnectivity between the same brain regions. Using resting state eyes-closed functional imaging and independent component analysis on a multi-site data that included 151 schizophrenia patients and 163 age- and gender matched healthy controls, we decomposed the functional brain data into 100 components and identified 47 as functionally relevant intrinsic connectivity networks. We subsequently evaluated group differences in functional network connectivity, both in a static sense, computed as the pairwise Pearson correlations between the full network time courses (5.4 minutes in length), and a dynamic sense, computed using sliding windows (44 s in length) and k-means clustering to characterize five discrete functional connectivity states. Static connectivity analysis revealed that compared to healthy controls, patients show significantly stronger connectivity, i.e., hyperconnectivity, between the thalamus and sensory networks (auditory, motor and visual), as well as reduced connectivity (hypoconnectivity) between sensory networks from all modalities. Dynamic analysis suggests that (1), on average, schizophrenia patients spend much less time than healthy controls in states typified by strong, large-scale connectivity, and (2), that abnormal connectivity patterns are more pronounced during these connectivity states. In particular, states exhibiting cortical-subcortical antagonism (anti-correlations) and strong positive connectivity between sensory networks are those that show the group differences of thalamic hyperconnectivity and sensory hypoconnectivity. Group

  12. Integrative Analysis of Transcriptomic and Epigenomic Data to Reveal Regulation Patterns for BMD Variation.

    PubMed

    Zhang, Ji-Gang; Tan, Li-Jun; Xu, Chao; He, Hao; Tian, Qing; Zhou, Yu; Qiu, Chuan; Chen, Xiang-Ding; Deng, Hong-Wen

    2015-01-01

    Integration of multiple profiling data and construction of functional gene networks may provide additional insights into the molecular mechanisms of complex diseases. Osteoporosis is a worldwide public health problem, but the complex gene-gene interactions, post-transcriptional modifications and regulation of functional networks are still unclear. To gain a comprehensive understanding of osteoporosis etiology, transcriptome gene expression microarray, epigenomic miRNA microarray and methylome sequencing were performed simultaneously in 5 high hip BMD (Bone Mineral Density) subjects and 5 low hip BMD subjects. SPIA (Signaling Pathway Impact Analysis) and PCST (Prize Collecting Steiner Tree) algorithm were used to perform pathway-enrichment analysis and construct the interaction networks. Through integrating the transcriptomic and epigenomic data, firstly we identified 3 genes (FAM50A, ZNF473 and TMEM55B) and one miRNA (hsa-mir-4291) which showed the consistent association evidence from both gene expression and methylation data; secondly in network analysis we identified an interaction network module with 12 genes and 11 miRNAs including AKT1, STAT3, STAT5A, FLT3, hsa-mir-141 and hsa-mir-34a which have been associated with BMD in previous studies. This module revealed the crosstalk among miRNAs, mRNAs and DNA methylation and showed four potential regulatory patterns of gene expression to influence the BMD status. In conclusion, the integration of multiple layers of omics can yield in-depth results than analysis of individual omics data respectively. Integrative analysis from transcriptomics and epigenomic data improves our ability to identify causal genetic factors, and more importantly uncover functional regulation pattern of multi-omics for osteoporosis etiology.

  13. "Hand down, man down." Analysis of defensive adjustments in response to the hot hand in basketball using novel defense metrics.

    PubMed

    Csapo, Peter; Raab, Markus

    2014-01-01

    The hot-hand phenomenon, according to which a player's performance is significantly elevated during certain phases relative to the expected performance based on the player's base rate, has left many researchers and fans in basketball puzzled: The vast majority of players, coaches and fans believe in its existence but statistical evidence supporting this belief has been scarce. It has frequently been argued that the hot hand in basketball is unobservable because of strategic adjustments and defensive interference of the opposing team. We use a dataset with novel metrics, such as the number of defenders and the defensive intensity for each shot attempt, which enable us to directly measure defensive pressure. First, we examine how the shooting percentage of NBA players changes relative to the attributes of each metric. We find that it is of lesser importance by how many defenders a player is guarded but that defensive intensity, e.g., whether a defender raises his hand when his opponent shoots, has a larger impact on shot difficulty. Second, we explore how the underlying metrics and shooting accuracy change as a function of streak length. Our results indicate that defensive pressure and shot difficulty increase (decrease) during hot (cold) streaks, so that defenders seem to behave according to the hot-hand belief and try to force hot players into more difficult shots. However, we find that shooting percentages of presumably hot players do not increase and that shooting performance is not related to streakiness, so that the defenders' hot-hand behavior cannot be considered ecologically rational. Therefore, we are unable to find evidence in favor of the hot-hand effect even when accounting for defensive pressure.

  14. Network analysis reveals that bacteria and fungi form modules that correlate independently with soil parameters.

    PubMed

    de Menezes, Alexandre B; Prendergast-Miller, Miranda T; Richardson, Alan E; Toscas, Peter; Farrell, Mark; Macdonald, Lynne M; Baker, Geoff; Wark, Tim; Thrall, Peter H

    2015-08-01

    Network and multivariate statistical analyses were performed to determine interactions between bacterial and fungal community terminal restriction length polymorphisms as well as soil properties in paired woodland and pasture sites. Canonical correspondence analysis (CCA) revealed that shifts in woodland community composition correlated with soil dissolved organic carbon, while changes in pasture community composition correlated with moisture, nitrogen and phosphorus. Weighted correlation network analysis detected two distinct microbial modules per land use. Bacterial and fungal ribotypes did not group separately, rather all modules comprised of both bacterial and fungal ribotypes. Woodland modules had a similar fungal : bacterial ribotype ratio, while in the pasture, one module was fungal dominated. There was no correspondence between pasture and woodland modules in their ribotype composition. The modules had different relationships to soil variables, and these contrasts were not detected without the use of network analysis. This study demonstrated that fungi and bacteria, components of the soil microbial communities usually treated as separate functional groups as in a CCA approach, were co-correlated and formed distinct associations in these adjacent habitats. Understanding these distinct modular associations may shed more light on their niche space in the soil environment, and allow a more realistic description of soil microbial ecology and function.

  15. Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma.

    PubMed

    Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

    2015-11-19

    Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks' robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

  16. Differential Network Analysis Reveals Evolutionary Complexity in Secondary Metabolism of Rauvolfia serpentina over Catharanthus roseus

    PubMed Central

    Pathania, Shivalika; Bagler, Ganesh; Ahuja, Paramvir S.

    2016-01-01

    Comparative co-expression analysis of multiple species using high-throughput data is an integrative approach to determine the uniformity as well as diversification in biological processes. Rauvolfia serpentina and Catharanthus roseus, both members of Apocyanacae family, are reported to have remedial properties against multiple diseases. Despite of sharing upstream of terpenoid indole alkaloid pathway, there is significant diversity in tissue-specific synthesis and accumulation of specialized metabolites in these plants. This led us to implement comparative co-expression network analysis to investigate the modules and genes responsible for differential tissue-specific expression as well as species-specific synthesis of metabolites. Toward these goals differential network analysis was implemented to identify candidate genes responsible for diversification of metabolites profile. Three genes were identified with significant difference in connectivity leading to differential regulatory behavior between these plants. These genes may be responsible for diversification of secondary metabolism, and thereby for species-specific metabolite synthesis. The network robustness of R. serpentina, determined based on topological properties, was also complemented by comparison of gene-metabolite networks of both plants, and may have evolved to have complex metabolic mechanisms as compared to C. roseus under the influence of various stimuli. This study reveals evolution of complexity in secondary metabolism of R. serpentina, and key genes that contribute toward diversification of specific metabolites. PMID:27588023

  17. Comprehensive profiling of lysine acetylproteome analysis reveals diverse functions of lysine acetylation in common wheat

    PubMed Central

    Zhang, Yumei; Song, Limin; Liang, Wenxing; Mu, Ping; Wang, Shu; Lin, Qi

    2016-01-01

    Lysine acetylation of proteins, a dynamic and reversible post-translational modification, plays a critical regulatory role in both eukaryotes and prokaryotes. Several researches have been carried out on acetylproteome in plants. However, until now, there have been no data on common wheat, the major cereal crop in the world. In this study, we performed a global acetylproteome analysis of common wheat variety (Triticum aestivum L.), Chinese Spring. In total, 416 lysine modification sites were identified on 277 proteins, which are involved in a wide variety of biological processes. Consistent with previous studies, a large proportion of the acetylated proteins are involved in metabolic process. Interestingly, according to the functional enrichment analysis, 26 acetylated proteins are involved in photosynthesis and Calvin cycle, suggesting an important role of lysine acetylation in these processes. Moreover, protein interaction network analysis reveals that diverse interactions are modulated by protein acetylation. These data represent the first report of acetylome in common wheat and serve as an important resource for exploring the physiological role of lysine acetylation in this organism and likely in all plants. PMID:26875666

  18. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis

    NASA Astrophysics Data System (ADS)

    Li, Yue; Zhang, Zhaolei

    2014-11-01

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  19. Molecular genetic analysis of Drosophila eyes absent mutants reveals an eye enhancer element.

    PubMed Central

    Zimmerman, J E; Bui, Q T; Liu, H; Bonini, N M

    2000-01-01

    The eyes absent (eya) gene is critical for normal eye development in Drosophila and is highly conserved to vertebrates. To define regions of the gene critical for eye function, we have defined the mutations in the four viable eya alleles. Two of these mutations are eye specific and undergo transvection with other mutations in the gene. These were found to be deletion mutations that remove regulatory sequence critical for eye cell expression of the gene. Two other viable alleles cause a reduced eye phenotype and affect the function of the gene in additional tissues, such as the ocelli. These mutations were found to be insertion mutations of different transposable elements within the 5' UTR of the transcript. Detailed analysis of one of these revealed that the transposable element has become subject to regulation by eye enhancer sequences of the eya gene, disrupting normal expression of EYA in the eye. More extended analysis of the deletion region in the eye-specific alleles indicated that the deleted region defines an enhancer that activates gene expression in eye progenitor cells. This enhancer is responsive to ectopic expression of the eyeless gene. This analysis has defined a critical regulatory region required for proper eye expression of the eya gene. PMID:10628984

  20. Genomic and physiological analysis reveals versatile metabolic capacity of deep-sea Photobacterium phosphoreum ANT-2200.

    PubMed

    Zhang, Sheng-Da; Santini, Claire-Lise; Zhang, Wei-Jia; Barbe, Valérie; Mangenot, Sophie; Guyomar, Charlotte; Garel, Marc; Chen, Hai-Tao; Li, Xue-Gong; Yin, Qun-Jian; Zhao, Yuan; Armengaud, Jean; Gaillard, Jean-Charles; Martini, Séverine; Pradel, Nathalie; Vidaud, Claude; Alberto, François; Médigue, Claudine; Tamburini, Christian; Wu, Long-Fei

    2016-05-01

    Bacteria of the genus Photobacterium thrive worldwide in oceans and show substantial eco-physiological diversity including free-living, symbiotic and piezophilic life styles. Genomic characteristics underlying this variability across species are poorly understood. Here we carried out genomic and physiological analysis of Photobacterium phosphoreum strain ANT-2200, the first deep-sea luminous bacterium of which the genome has been sequenced. Using optical mapping we updated the genomic data and reassembled it into two chromosomes and a large plasmid. Genomic analysis revealed a versatile energy metabolic potential and physiological analysis confirmed its growth capacity by deriving energy from fermentation of glucose or maltose, by respiration with formate as electron donor and trimethlyamine N-oxide (TMAO), nitrate or fumarate as electron acceptors, or by chemo-organo-heterotrophic growth in rich media. Despite that it was isolated at a site with saturated dissolved oxygen, the ANT-2200 strain possesses four gene clusters coding for typical anaerobic enzymes, the TMAO reductases. Elevated hydrostatic pressure enhances the TMAO reductase activity, mainly due to the increase of isoenzyme TorA1. The high copy number of the TMAO reductase isoenzymes and pressure-enhanced activity might imply a strategy developed by bacteria to adapt to deep-sea habitats where the instant TMAO availability may increase with depth.

  1. Topological robustness analysis of protein interaction networks reveals key targets for overcoming chemotherapy resistance in glioma

    NASA Astrophysics Data System (ADS)

    Azevedo, Hátylas; Moreira-Filho, Carlos Alberto

    2015-11-01

    Biological networks display high robustness against random failures but are vulnerable to targeted attacks on central nodes. Thus, network topology analysis represents a powerful tool for investigating network susceptibility against targeted node removal. Here, we built protein interaction networks associated with chemoresistance to temozolomide, an alkylating agent used in glioma therapy, and analyzed their modular structure and robustness against intentional attack. These networks showed functional modules related to DNA repair, immunity, apoptosis, cell stress, proliferation and migration. Subsequently, network vulnerability was assessed by means of centrality-based attacks based on the removal of node fractions in descending orders of degree, betweenness, or the product of degree and betweenness. This analysis revealed that removing nodes with high degree and high betweenness was more effective in altering networks’ robustness parameters, suggesting that their corresponding proteins may be particularly relevant to target temozolomide resistance. In silico data was used for validation and confirmed that central nodes are more relevant for altering proliferation rates in temozolomide-resistant glioma cell lines and for predicting survival in glioma patients. Altogether, these results demonstrate how the analysis of network vulnerability to topological attack facilitates target prioritization for overcoming cancer chemoresistance.

  2. Potential microRNA-mediated oncogenic intercellular communication revealed by pan-cancer analysis.

    PubMed

    Li, Yue; Zhang, Zhaolei

    2014-11-18

    Carcinogenesis consists of oncogenesis and metastasis, and intriguingly microRNAs (miRNAs) are involved in both processes. Although aberrant miRNA activities are prevalent in diverse tumor types, the exact mechanisms for how they regulate cancerous processes are not always clear. To this end, we performed a large-scale pan-cancer analysis via a novel probabilistic approach to infer recurrent miRNA-target interactions implicated in 12 cancer types using data from The Cancer Genome Atlas. We discovered ~20,000 recurrent miRNA regulations, which are enriched for cancer-related miRNAs/genes. Notably, miRNA 200 family (miR-200/141/429) is among the most prominent miRNA regulators, which is known to be involved in metastasis. Importantly, the recurrent miRNA regulatory network is not only enriched for cancer pathways but also for extracellular matrix (ECM) organization and ECM-receptor interactions. The results suggest an intriguing cancer mechanism involving miRNA-mediated cell-to-cell communication, which possibly involves delivery of tumorigenic miRNA messengers to adjacent cells via exosomes. Finally, survival analysis revealed 414 recurrent-prognostic associations, where both gene and miRNA involved in each interaction conferred significant prognostic power in one or more cancer types. Together, our comprehensive pan-cancer analysis provided not only biological insights into metastasis but also brought to bear the clinical relevance of the proposed recurrent miRNA-gene associations.

  3. Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids.

    PubMed

    Schmitz, Alexander; Fischer, Sabine C; Mattheyer, Christian; Pampaloni, Francesco; Stelzer, Ernst H K

    2017-03-03

    Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid's size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 10(5) to 1 × 10(6 )cells/mm(3). Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture.

  4. Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids

    PubMed Central

    Schmitz, Alexander; Fischer, Sabine C.; Mattheyer, Christian; Pampaloni, Francesco; Stelzer, Ernst H. K.

    2017-01-01

    Three-dimensional multicellular aggregates such as spheroids provide reliable in vitro substitutes for tissues. Quantitative characterization of spheroids at the cellular level is fundamental. We present the first pipeline that provides three-dimensional, high-quality images of intact spheroids at cellular resolution and a comprehensive image analysis that completes traditional image segmentation by algorithms from other fields. The pipeline combines light sheet-based fluorescence microscopy of optically cleared spheroids with automated nuclei segmentation (F score: 0.88) and concepts from graph analysis and computational topology. Incorporating cell graphs and alpha shapes provided more than 30 features of individual nuclei, the cellular neighborhood and the spheroid morphology. The application of our pipeline to a set of breast carcinoma spheroids revealed two concentric layers of different cell density for more than 30,000 cells. The thickness of the outer cell layer depends on a spheroid’s size and varies between 50% and 75% of its radius. In differently-sized spheroids, we detected patches of different cell densities ranging from 5 × 105 to 1 × 106 cells/mm3. Since cell density affects cell behavior in tissues, structural heterogeneities need to be incorporated into existing models. Our image analysis pipeline provides a multiscale approach to obtain the relevant data for a system-level understanding of tissue architecture. PMID:28255161

  5. Microarray analysis reveals altered circulating microRNA expression in mice infected with Coxsackievirus B3

    PubMed Central

    Sun, Chaoyu; Tong, Lei; Zhao, Wenran; Wang, Yan; Meng, Yuan; Lin, Lexun; Liu, Bingchen; Zhai, Yujia; Zhong, Zhaohua; Li, Xueqi

    2016-01-01

    Coxsackievirus B3 (CVB3) is a common causative agent in the development of inflammatory cardiomyopathy. However, whether the expression of peripheral blood microRNAs (miRNAs) is altered in this process is unknown. The present study investigated changes to miRNA expression in the peripheral blood of CVB3-infected mice. Utilizing miRNA microarray technology, differential miRNA expression was examined between normal and CVB3-infected mice. The present results suggest that specific miRNAs were differentially expressed in the peripheral blood of mice infected with CVB3, varying with infection duration. Using miRNA microarray analysis, a total of 96 and 89 differentially expressed miRNAs were identified in the peripheral blood of mice infected with CVB3 for 3 and 6 days, respectively. Quantitative polymerase chain reaction was used to validate differentially expressed miRNAs, revealing a consistency of these results with the miRNA microarray analysis results. The biological functions of the differentially expressed miRNAs were then predicted by bioinformatics analysis. The potential biological roles of differentially expressed miRNAs included hypertrophic cardiomyopathy, dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy. These results may provide important insights into the mechanisms responsible for the progression of CVB3 infection. PMID:27698715

  6. Integrative Analysis of Cellular Morphometric Context Reveals Clinically Relevant Signatures in Lower Grade Glioma⋆

    PubMed Central

    Han, Ju; Wang, Yunfu; Cai, Weidong; Borowsky, Alexander; Parvin, Bahram; Chang, Hang

    2016-01-01

    Integrative analysis based on quantitative representation of whole slide images (WSIs) in a large histology cohort may provide predictive models of clinical outcome. On one hand, the efficiency and effectiveness of such representation is hindered as a result of large technical variations (e.g., fixation, staining) and biological heterogeneities (e.g., cell type, cell state) that are always present in a large cohort. On the other hand, perceptual interpretation/validation of important multivariate phenotypic signatures are often difficult due to the loss of visual information during feature transformation in hyperspace. To address these issues, we propose a novel approach for integrative analysis based on cellular morphometric context, which is a robust representation of WSI, with the emphasis on tumor architecture and tumor heterogeneity, built upon cellular level morphometric features within the spatial pyramid matching (SPM) framework. The proposed approach is applied to The Cancer Genome Atlas (TCGA) lower grade glioma (LGG) cohort, where experimental results (i) reveal several clinically relevant cellular morphometric types, which enables both perceptual interpretation/validation and further investigation through gene set enrichment analysis; and (ii) indicate the significantly increased survival rates in one of the cellular morphometric context subtypes derived from the cellular morphometric context. PMID:28018994

  7. Integrated systems analysis reveals a molecular network underlying autism spectrum disorders.

    PubMed

    Li, Jingjing; Shi, Minyi; Ma, Zhihai; Zhao, Shuchun; Euskirchen, Ghia; Ziskin, Jennifer; Urban, Alexander; Hallmayer, Joachim; Snyder, Michael

    2014-12-30

    Autism is a complex disease whose etiology remains elusive. We integrated previously and newly generated data and developed a systems framework involving the interactome, gene expression and genome sequencing to identify a protein interaction module with members strongly enriched for autism candidate genes. Sequencing of 25 patients confirmed the involvement of this module in autism, which was subsequently validated using an independent cohort of over 500 patients. Expression of this module was dichotomized with a ubiquitously expressed subcomponent and another subcomponent preferentially expressed in the corpus callosum, which was significantly affected by our identified mutations in the network center. RNA-sequencing of the corpus callosum from patients with autism exhibited extensive gene mis-expression in this module, and our immunochemical analysis showed that the human corpus callosum is predominantly populated by oligodendrocyte cells. Analysis of functional genomic data further revealed a significant involvement of this module in the development of oligodendrocyte cells in mouse brain. Our analysis delineates a natural network involved in autism, helps uncover novel candidate genes for this disease and improves our understanding of its molecular pathology.

  8. Comparative Analysis of 35 Basidiomycete Genomes Reveals Diversity and Uniqueness of the Phylum

    SciTech Connect

    Riley, Robert; Salamov, Asaf; Otillar, Robert; Fagnan, Kirsten; Boussau, Bastien; Brown, Daren; Henrissat, Bernard; Levasseur, Anthony; Held, Benjamin; Nagy, Laszlo; Floudas, Dimitris; Morin, Emmanuelle; Manning, Gerard; Baker, Scott; Martin, Francis; Blanchette, Robert; Hibbett, David; Grigoriev, Igor V.

    2013-03-11

    Fungi of the phylum Basidiomycota (basidiomycetes), make up some 37percent of the described fungi, and are important in forestry, agriculture, medicine, and bioenergy. This diverse phylum includes symbionts, pathogens, and saprobes including wood decaying fungi. To better understand the diversity of this phylum we compared the genomes of 35 basidiomycete fungi including 6 newly sequenced genomes. The genomes of basidiomycetes span extremes of genome size, gene number, and repeat content. A phylogenetic tree of Basidiomycota was generated using the Phyldog software, which uses all available protein sequence data to simultaneously infer gene and species trees. Analysis of core genes reveals that some 48percent of basidiomycete proteins are unique to the phylum with nearly half of those (22percent) comprising proteins found in only one organism. Phylogenetic patterns of plant biomass-degrading genes suggest a continuum rather than a sharp dichotomy between the white rot and brown rot modes of wood decay among the members of Agaricomycotina subphylum. There is a correlation of the profile of certain gene families to nutritional mode in Agaricomycotina. Based on phylogenetically-informed PCA analysis of such profiles, we predict that that Botryobasidium botryosum and Jaapia argillacea have properties similar to white rot species, although neither has liginolytic class II fungal peroxidases. Furthermore, we find that both fungi exhibit wood decay with white rot-like characteristics in growth assays. Analysis of the rate of discovery of proteins with no or few homologs suggests the high value of continued sequencing of basidiomycete fungi.

  9. A novel meta-analysis approach of cancer transcriptomes reveals prevailing transcriptional networks in cancer cells.

    PubMed

    Niida, Atsushi; Imoto, Seiya; Nagasaki, Masao; Yamaguchi, Rui; Miyano, Satoru

    2010-01-01

    Although microarray technology has revealed transcriptomic diversities underlining various cancer phenotypes, transcriptional programs controlling them have not been well elucidated. To decode transcriptional programs governing cancer transcriptomes, we have recently developed a computational method termed EEM, which searches for expression modules from prescribed gene sets defined by prior biological knowledge like TF binding motifs. In this paper, we extend our EEM approach to predict cancer transcriptional networks. Starting from functional TF binding motifs and expression modules identified by EEM, we predict cancer transcriptional networks containing regulatory TFs, associated GO terms, and interactions between TF binding motifs. To systematically analyze transcriptional programs in broad types of cancer, we applied our EEM-based network prediction method to 122 microarray datasets collected from public databases. The data sets contain about 15000 experiments for tumor samples of various tissue origins including breast, colon, lung etc. This EEM based meta-analysis successfully revealed a prevailing cancer transcriptional network which functions in a large fraction of cancer transcriptomes; they include cell-cycle and immune related sub-networks. This study demonstrates broad applicability of EEM, and opens a way to comprehensive understanding of transcriptional networks in cancer cells.

  10. Paternal uniparental disomy for chromosome 1 revealed by molecular analysis of a patient with pycnodysostosis.

    PubMed Central

    Gelb, B D; Willner, J P; Dunn, T M; Kardon, N B; Verloes, A; Poncin, J; Desnick, R J

    1998-01-01

    Molecular analysis of a patient affected by the autosomal recessive skeletal dysplasia, pycnodysostosis (cathepsin K deficiency; MIM 265800), revealed homozygosity for a novel missense mutation (A277V). Since the A277V mutation was carried by the patient's father but not by his mother, who had two normal cathepsin K alleles, paternal uniparental disomy was suspected. Karyotyping of the patient and of both parents was normal, and high-resolution cytogenetic analyses of chromosome 1, to which cathepsin K is mapped, revealed no abnormalities. Evaluation of polymorphic DNA markers spanning chromosome 1 demonstrated that the patient had inherited two paternal chromosome 1 homologues, whereas alleles for markers from other chromosomes were inherited in a Mendelian fashion. The patient was homoallelic for informative markers mapping near the chromosome 1 centromere, but he was heteroallelic for markers near both telomeres, establishing that the paternal uniparental disomy with partial isodisomy was caused by a meiosis II nondisjunction event. Phenotypically, the patient had normal birth height and weight, had normal psychomotor development at age 7 years, and had only the usual features of pycnodysostosis. This patient represents the first case of paternal uniparental disomy of chromosome 1 and provides conclusive evidence that paternally derived genes on human chromosome 1 are not imprinted. PMID:9529353

  11. Adaptations to a subterranean environment and longevity revealed by the analysis of mole rat genomes

    PubMed Central

    Fang, Xiaodong; Seim, Inge; Huang, Zhiyong; Gerashchenko, Maxim V.; Xiong, Zhiqiang; Turanov, Anton A.; Zhu, Yabing; Lobanov, Alexei V.; Fan, Dingding; Yim, Sun Hee; Yao, Xiaoming; Ma, Siming; Yang, Lan; Lee, Sang-Goo; Kim, Eun Bae; Bronson, Roderick T.; Šumbera, Radim; Buffenstein, Rochelle; Zhou, Xin; Krogh, Anders; Park, Thomas J.; Zhang, Guojie; Wang, Jun; Gladyshev, Vadim N.

    2014-01-01

    SUMMARY Subterranean mammals spend their lives in dark, unventilated environments rich in carbon dioxide and ammonia, and low in oxygen. Many of these animals are also long-lived and exhibit reduced aging-associated diseases, such as neurodegenerative disorders and cancer. We sequenced the genome of the Damaraland mole rat (DMR, Fukomys damarensis) and improved the genome assembly of the naked mole rat (NMR, Heterocephalus glaber). Comparative genome analysis, along with transcriptomes of related subterranean rodents, reveal candidate molecular adaptations for subterranean life and longevity, including a divergent insulin peptide, expression of oxygen-carrying globins in the brain, prevention of high CO2-induced pain perception, and enhanced ammonia detoxification. Juxtaposition of the genomes of DMR and other more conventional animals with the genome of NMR revealed several truly exceptional NMR features: unusual thermogenesis, aberrant melatonin system, pain insensitivity, and novel processing of 28S rRNA. Together, the new genomes and transcriptomes extend our understanding of subterranean adaptations, stress resistance and longevity. PMID:25176646

  12. Genetic relationships of the Japanese persimmon Diospyros kaki (Ebenaceae) and related species revealed by SSR analysis.

    PubMed

    Guo, D L; Luo, Z R

    2011-06-07

    Simple sequence repeat (SSR) molecular markers based on 18 primers were employed to study the genetic relationship of Japanese persimmon (Diospyros kaki) specimens. Two hundred and sixty-two bands were detected in 30 Japanese persimmon samples, including 14 Japanese and 10 Chinese genotypes of Japanese persimmon (Diospyros kaki) and six related species, D. lotus, D. glaucifolia, D. oleifera, D. rhombifolia, D. virginiana, and Jinzaoshi (unclassified - previously indicated to be D. kaki). All SSR primers developed from D. kaki were successfully employed to reveal the polymorphism in other species of Diospyros. Most of the primers were highly polymorphic, with a degree of polymorphism equal to or higher than 0.66. The results from the neighbor-joining dendrogram and the principal coordinate analysis diagram were the same; i.e., the Chinese and Japanese genotypes and related species were separated and the relationships revealed were consistent with the known pedigrees. We also concluded that 'Xiangxitianshi' from Xiangxi municipality, Hunan Province, China, is actually a sport or somaclonal variant of 'Maekawa-Jirou', and that 'Jinzaoshi' should be classified as a distinct species of Diospyros. We found that SSR markers are a valuable tool for the estimation of genetic diversity and divergence in Diospyros.

  13. Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations.

    PubMed

    Förster, Frank; Beisser, Daniela; Grohme, Markus A; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C; Shkumatov, Alexander V; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant.

  14. Analysis of self-overlap reveals trade-offs in plankton swimming trajectories.

    PubMed

    Bianco, Giuseppe; Mariani, Patrizio; Visser, Andre W; Mazzocchi, Maria Grazia; Pigolotti, Simone

    2014-07-06

    Movement is a fundamental behaviour of organisms that not only brings about beneficial encounters with resources and mates, but also at the same time exposes the organism to dangerous encounters with predators. The movement patterns adopted by organisms should reflect a balance between these contrasting processes. This trade-off can be hypothesized as being evident in the behaviour of plankton, which inhabit a dilute three-dimensional environment with few refuges or orienting landmarks. We present an analysis of the swimming path geometries based on a volumetric Monte Carlo sampling approach, which is particularly adept at revealing such trade-offs by measuring the self-overlap of the trajectories. Application of this method to experimentally measured trajectories reveals that swimming patterns in copepods are shaped to efficiently explore volumes at small scales, while achieving a large overlap at larger scales. Regularities in the observed trajectories make the transition between these two regimes always sharper than in randomized trajectories or as predicted by random walk theory. Thus, real trajectories present a stronger separation between exploration for food and exposure to predators. The specific scale and features of this transition depend on species, gender and local environmental conditions, pointing at adaptation to state and stage-dependent evolutionary trade-offs.

  15. A domain-centric analysis of oomycete plant pathogen genomes reveals unique protein organization.

    PubMed

    Seidl, Michael F; Van den Ackerveken, Guido; Govers, Francine; Snel, Berend

    2011-02-01

    Oomycetes comprise a diverse group of organisms that morphologically resemble fungi but belong to the stramenopile lineage within the supergroup of chromalveolates. Recent studies have shown that plant pathogenic oomycetes have expanded gene families that are possibly linked to their pathogenic lifestyle. We analyzed the protein domain organization of 67 eukaryotic species including four oomycete and five fungal plant pathogens. We detected 246 expanded domains in fungal and oomycete plant pathogens. The analysis of genes differentially expressed during infection revealed a significant enrichment of genes encoding expanded domains as well as signal peptides linking a substantial part of these genes to pathogenicity. Overrepresentation and clustering of domain abundance profiles revealed domains that might have important roles in host-pathogen interactions but, as yet, have not been linked to pathogenicity. The number of distinct domain combinations (bigrams) in oomycetes was significantly higher than in fungi. We identified 773 oomycete-specific bigrams, with the majority composed of domains common to eukaryotes. The analyses enabled us to link domain content to biological processes such as host-pathogen interaction, nutrient uptake, or suppression and elicitation of plant immune responses. Taken together, this study represents a comprehensive overview of the domain repertoire of fungal and oomycete plant pathogens and points to novel features like domain expansion and species-specific bigram types that could, at least partially, explain why oomycetes are such remarkable plant pathogens.

  16. Analysis of self-overlap reveals trade-offs in plankton swimming trajectories

    PubMed Central

    Bianco, Giuseppe; Mariani, Patrizio; Visser, Andre W.; Mazzocchi, Maria Grazia; Pigolotti, Simone

    2014-01-01

    Movement is a fundamental behaviour of organisms that not only brings about beneficial encounters with resources and mates, but also at the same time exposes the organism to dangerous encounters with predators. The movement patterns adopted by organisms should reflect a balance between these contrasting processes. This trade-off can be hypothesized as being evident in the behaviour of plankton, which inhabit a dilute three-dimensional environment with few refuges or orienting landmarks. We present an analysis of the swimming path geometries based on a volumetric Monte Carlo sampling approach, which is particularly adept at revealing such trade-offs by measuring the self-overlap of the trajectories. Application of this method to experimentally measured trajectories reveals that swimming patterns in copepods are shaped to efficiently explore volumes at small scales, while achieving a large overlap at larger scales. Regularities in the observed trajectories make the transition between these two regimes always sharper than in randomized trajectories or as predicted by random walk theory. Thus, real trajectories present a stronger separation between exploration for food and exposure to predators. The specific scale and features of this transition depend on species, gender and local environmental conditions, pointing at adaptation to state and stage-dependent evolutionary trade-offs. PMID:24789560

  17. Transcriptome Analysis in Tardigrade Species Reveals Specific Molecular Pathways for Stress Adaptations

    PubMed Central

    Förster, Frank; Beisser, Daniela; Grohme, Markus A.; Liang, Chunguang; Mali, Brahim; Siegl, Alexander Matthias; Engelmann, Julia C.; Shkumatov, Alexander V.; Schokraie, Elham; Müller, Tobias; Schnölzer, Martina; Schill, Ralph O.; Frohme, Marcus; Dandekar, Thomas

    2012-01-01

    Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade Milnesium tardigradum were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from Hypsibius dujardini, revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for M. tardigradum are different from typical motifs known from higher animals. M. tardigradum and H. dujardini protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of M. tardigradum. These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and M. tardigradum in particular so highly stress resistant. PMID:22563243

  18. Quantitative Analysis of the Human Airway Microbial Ecology Reveals a Pervasive Signature for Cystic Fibrosis

    PubMed Central

    Blainey, Paul C.; Milla, Carlos E.; Cornfield, David N.; Quake, Stephen R.

    2014-01-01

    Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the CF transmembrane conductance regulator. Disruption of electrolyte homeostasis at mucosal surfaces leads to severe lung, pancreatic, intestinal, hepatic, and reproductive abnormalities. Loss of lung function as a result of chronic lung disease is the primary cause of death from CF. Using high-throughput sequencing to survey microbes in the sputum of 16 CF patients and 9 control individuals, we identified diverse microbial communities in the healthy samples, contravening conventional wisdom that healthy airways are not significantly colonized. Comparing these communities with those from the CF patients revealed significant differences in microbial ecology, including differential representation of uncultivated phylotypes. Despite patient-specific differences, our analysis revealed a focal microbial profile characteristic of CF. The profile differentiated case and control groups even when classically recognized CF pathogens were excluded. As a control, lung explant tissues were also processed from a group of patients with pulmonary disease. The findings in lung tissue corroborated the presence of taxa identified in the sputum samples. Comparing the sequencing results with clinical data indicated that diminished microbial diversity is associated with severity of pulmonary inflammation within our adult CF cohort. PMID:23019655

  19. Stable isotope analysis of vertebrae reveals ontogenetic changes in habitat in an endothermic pelagic shark.

    PubMed

    Carlisle, Aaron B; Goldman, Kenneth J; Litvin, Steven Y; Madigan, Daniel J; Bigman, Jennifer S; Swithenbank, Alan M; Kline, Thomas C; Block, Barbara A

    2015-01-22

    Ontogenetic changes in habitat are driven by shifting life-history requirements and play an important role in population dynamics. However, large portions of the life history of many pelagic species are still poorly understood or unknown. We used a novel combination of stable isotope analysis of vertebral annuli, Bayesian mixing models, isoscapes and electronic tag data to reconstruct ontogenetic patterns of habitat and resource use in a pelagic apex predator, the salmon shark (Lamna ditropis). Results identified the North Pacific Transition Zone as the major nursery area for salmon sharks and revealed an ontogenetic shift around the age of maturity from oceanic to increased use of neritic habitats. The nursery habitat may reflect trade-offs between prey availability, predation pressure and thermal constraints on juvenile endothermic sharks. The ontogenetic shift in habitat coincided with a reduction of isotopic niche, possibly reflecting specialization upon particular prey or habitats. Using tagging data to inform Bayesian isotopic mixing models revealed that adult sharks primarily use neritic habitats of Alaska yet receive a trophic subsidy from oceanic habitats. Integrating the multiple methods used here provides a powerful approach to retrospectively study the ecology and life history of migratory species throughout their ontogeny.

  20. Genetic analysis reveals candidate species in the Scinax catharinae clade (Amphibia: Anura) from Central Brazil

    PubMed Central

    Nogueira, Lídia; Solé, Mirco; Siqueira, Sérgio; Affonso, Paulo Roberto Antunes de Mello; Strüssmann, Christine; Sampaio, Iracilda

    2016-01-01

    Abstract Scinax (Anura: Hylidae) is a species-rich genus of amphibians (113 spp.), divided into five species groups by morphological features. Cladistic analyses however revealed only two monophyletic clades in these groups: Scinax catharinae and Scinax ruber. Most species from the S. catharinae clade are found in Atlantic rainforest, except for Scinax canastrensis,S. centralis, S. luizotavioi, S. machadoi,S. pombali and S. skaios. In the present work, specimens of Scinax collected in Chapada dos Guimarães, central Brazil, were morphologically compatible with species from theS. catharinae group. On the other hand, genetic analysis based on mitochondrial (16S and 12S) and nuclear (rhodopsin) sequences revealed a nucleotide divergence of 6 to 20% between Scinax sp. and other congeners from the Brazilian savannah (Cerrado). Accordingly, Bayesian inference placed Scinax sp. in the S. catharinae clade with high support values. Hence, these findings strongly indicate the presence of a new species in the S. catharinae clade from the southwestern portion of the Brazilian savannah. To be properly validated as a novel species, detailed comparative morphological and bioacustic studies with other taxa from Brazil such asS. canastrensis, S. centralis, S. luizotavioi, S. machadoi, S. pombali and S. skaios are required. PMID:27007898

  1. Genetic analysis reveals candidate species in the Scinax catharinae clade (Amphibia: Anura) from Central Brazil.

    PubMed

    Nogueira, Lídia; Solé, Mirco; Siqueira, Sérgio; Affonso, Paulo Roberto Antunes de Mello; Strüssmann, Christine; Sampaio, Iracilda

    2016-03-01

    Scinax (Anura: Hylidae) is a species-rich genus of amphibians (113 spp.), divided into five species groups by morphological features. Cladistic analyses however revealed only two monophyletic clades in these groups: Scinax catharinae and Scinax ruber. Most species from the S. catharinae clade are found in Atlantic rainforest, except for Scinax canastrensis,S. centralis, S. luizotavioi, S. machadoi,S. pombali and S. skaios. In the present work, specimens of Scinax collected in Chapada dos Guimarães, central Brazil, were morphologically compatible with species from theS. catharinae group. On the other hand, genetic analysis based on mitochondrial (16S and 12S) and nuclear (rhodopsin) sequences revealed a nucleotide divergence of 6 to 20% between Scinax sp. and other congeners from the Brazilian savannah (Cerrado). Accordingly, Bayesian inference placed Scinax sp. in the S. catharinae clade with high support values. Hence, these findings strongly indicate the presence of a new species in the S. catharinae clade from the southwestern portion of the Brazilian savannah. To be properly validated as a novel species, detailed comparative morphological and bioacustic studies with other taxa from Brazil such asS. canastrensis, S. centralis, S. luizotavioi, S. machadoi, S. pombali and S. skaios are required.

  2. Stable isotope analysis of vertebrae reveals ontogenetic changes in habitat in an endothermic pelagic shark

    PubMed Central

    Carlisle, Aaron B.; Goldman, Kenneth J.; Litvin, Steven Y.; Madigan, Daniel J.; Bigman, Jennifer S.; Swithenbank, Alan M.; Kline, Thomas C.; Block, Barbara A.

    2015-01-01

    Ontogenetic changes in habitat are driven by shifting life-history requirements and play an important role in population dynamics. However, large portions of the life history of many pelagic species are still poorly understood or unknown. We used a novel combination of stable isotope analysis of vertebral annuli, Bayesian mixing models, isoscapes and electronic tag data to reconstruct ontogenetic patterns of habitat and resource use in a pelagic apex predator, the salmon shark (Lamna ditropis). Results identified the North Pacific Transition Zone as the major nursery area for salmon sharks and revealed an ontogenetic shift around the age of maturity from oceanic to increased use of neritic habitats. The nursery habitat may reflect trade-offs between prey availability, predation pressure and thermal constraints on juvenile endothermic sharks. The ontogenetic shift in habitat coincided with a reduction of isotopic niche, possibly reflecting specialization upon particular prey or habitats. Using tagging data to inform Bayesian isotopic mixing models revealed that adult sharks primarily use neritic habitats of Alaska yet receive a trophic subsidy from oceanic habitats. Integrating the multiple methods used here provides a powerful approach to retrospectively study the ecology and life history of migratory species throughout their ontogeny. PMID:25621332

  3. Microarray analysis reveals novel features of the muscle aging process in men and women.

    PubMed

    Liu, Dongmei; Sartor, Maureen A; Nader, Gustavo A; Pistilli, Emidio E; Tanton, Leah; Lilly, Charles; Gutmann, Laurie; IglayReger, Heidi B; Visich, Paul S; Hoffman, Eric P; Gordon, Paul M

    2013-09-01

    To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women.

  4. Microarray Analysis Reveals Novel Features of the Muscle Aging Process in Men and Women

    PubMed Central

    2013-01-01

    To develop a global view of muscle transcriptional differences between older men and women and sex-specific aging, we obtained muscle biopsies from the biceps brachii of young and older men and women and profiled the whole-genome gene expression using microarray. A logistic regression-based method in combination with an intensity-based Bayesian moderated t test was used to identify significant sex- and aging-related gene functional groups. Our analysis revealed extensive sex differences in the muscle transcriptome of older individuals and different patterns of transcriptional changes with aging in men and women. In older women, we observed a coordinated transcriptional upregulation of immune activation, extracellular matrix remodeling, and lipids storage; and a downregulation of mitochondrial biogenesis and function and muscle regeneration. The effect of aging results in sexual dimorphic alterations in the skeletal muscle transcriptome, which may modify the risk for developing musculoskeletal and metabolic diseases in men and women. PMID:23418191

  5. Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis

    PubMed Central

    Vogel, Robert M.; Erez, Amir; Altan-Bonnet, Grégoire

    2016-01-01

    Despite progress in drug development, a quantitative and physiological understanding of how small-molecule inhibitors act on cells is lacking. Here, we measure the signalling and proliferative response of individual primary T-lymphocytes to a combination of antigen, cytokine and drug. We uncover two distinct modes of signalling inhibition: digital inhibition (the activated fraction of cells diminishes upon drug treatment, but active cells appear unperturbed), versus analogue inhibition (the activated fraction is unperturbed whereas activation response is diminished). We introduce a computational model of the signalling cascade that accounts for such inhibition dichotomy, and test the model predictions for the phenotypic variability of cellular responses. Finally, we demonstrate that the digital/analogue dichotomy of cellular response as revealed on short (signal transduction) timescales, translates into similar dichotomy on longer (proliferation) timescales. Our single-cell analysis of drug action illustrates the strength of quantitative approaches to translate in vitro pharmacology into functionally relevant cellular settings. PMID:27687249

  6. Metagenomic analysis reveals significant changes of microbial compositions and protective functions during drinking water treatment.

    PubMed

    Chao, Yuanqing; Ma, Liping; Yang, Ying; Ju, Feng; Zhang, Xu-Xiang; Wu, Wei-Min; Zhang, Tong

    2013-12-19

    The metagenomic approach was applied to characterize variations of microbial structure and functions in raw (RW) and treated water (TW) in a drinking water treatment plant (DWTP) at Pearl River Delta, China. Microbial structure was significantly influenced by the treatment processes, shifting from Gammaproteobacteria and Betaproteobacteria in RW to Alphaproteobacteria in TW. Further functional analysis indicated the basic metabolic functions of microorganisms in TW did not vary considerably. However, protective functions, i.e. glutathione synthesis genes in 'oxidative stress' and 'detoxification' subsystems, significantly increased, revealing the surviving bacteria may have higher chlorine resistance. Similar results were also found in glutathione metabolism pathway, which identified the major reaction for glutathione synthesis and supported more genes for glutathione metabolism existed in TW. This metagenomic study largely enhanced our knowledge about the influences of treatment processes, especially chlorination, on bacterial community structure and protective functions (e.g. glutathione metabolism) in ecosystems of DWTPs.

  7. Network-based diffusion analysis reveals cultural transmission of lobtail feeding in humpback whales.

    PubMed

    Allen, Jenny; Weinrich, Mason; Hoppitt, Will; Rendell, Luke

    2013-04-26

    We used network-based diffusion analysis to reveal the cultural spread of a naturally occurring foraging innovation, lobtail feeding, through a population of humpback whales (Megaptera novaeangliae) over a period of 27 years. Support for models with a social transmission component was 6 to 23 orders of magnitude greater than for models without. The spatial and temporal distribution of sand lance, a prey species, was also important in predicting the rate of acquisition. Our results, coupled with existing knowledge about song traditions, show that this species can maintain multiple independently evolving traditions in its populations. These insights strengthen the case that cetaceans represent a peak in the evolution of nonhuman culture, independent of the primate lineage.

  8. Metagenomic analysis of the pinewood nematode microbiome reveals a symbiotic relationship critical for xenobiotics degradation

    PubMed Central

    Cheng, Xin-Yue; Tian, Xue-Liang; Wang, Yun-Sheng; Lin, Ren-Miao; Mao, Zhen-Chuan; Chen, Nansheng; Xie, Bing-Yan

    2013-01-01

    Our recent research revealed that pinewood nematode (PWN) possesses few genes encoding enzymes for degrading α-pinene, which is the main compound in pine resin. In this study, we examined the role of PWN microbiome in xenobiotics detoxification by metagenomic and bacteria culture analyses. Functional annotation of metagenomes illustrated that benzoate degradation and its related metabolisms may provide the main metabolic pathways for xenobiotics detoxification in the microbiome, which is obviously different from that in PWN that uses cytochrome P450 metabolism as the main pathway for detoxification. The metabolic pathway of degrading α-pinene is complete in microbiome, but incomplete in PWN genome. Experimental analysis demonstrated that most of tested cultivable bacteria can not only survive the stress of 0.4% α-pinene, but also utilize α-pinene as carbon source for their growth. Our results indicate that PWN and its microbiome have established a potentially mutualistic symbiotic relationship with complementary pathways in detoxification metabolism. PMID:23694939

  9. Dichotomy of cellular inhibition by small-molecule inhibitors revealed by single-cell analysis

    NASA Astrophysics Data System (ADS)

    Vogel, Robert M.; Erez, Amir; Altan-Bonnet, Grégoire

    2016-09-01

    Despite progress in drug development, a quantitative and physiological understanding of how small-molecule inhibitors act on cells is lacking. Here, we measure the signalling and proliferative response of individual primary T-lymphocytes to a combination of antigen, cytokine and drug. We uncover two distinct modes of signalling inhibition: digital inhibition (the activated fraction of cells diminishes upon drug treatment, but active cells appear unperturbed), versus analogue inhibition (the activated fraction is unperturbed whereas activation response is diminished). We introduce a computational model of the signalling cascade that accounts for such inhibition dichotomy, and test the model predictions for the phenotypic variability of cellular responses. Finally, we demonstrate that the digital/analogue dichotomy of cellular response as revealed on short (signal transduction) timescales, translates into similar dichotomy on longer (proliferation) timescales. Our single-cell analysis of drug action illustrates the strength of quantitative approaches to translate in vitro pharmacology into functionally relevant cellular settings.

  10. Bifidobacterium asteroides PRL2011 Genome Analysis Reveals Clues for Colonization of the Insect Gut

    PubMed Central

    Bottacini, Francesca; Milani, Christian; Turroni, Francesca; Sánchez, Borja; Foroni, Elena; Duranti, Sabrina; Serafini, Fausta; Viappiani, Alice; Strati, Francesco; Ferrarini, Alberto; Delledonne, Massimo; Henrissat, Bernard; Coutinho, Pedro; Fitzgerald, Gerald F.; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

    2012-01-01

    Bifidobacteria are known as anaerobic/microaerophilic and fermentative microorganisms, which commonly inhabit the gastrointestinal tract of various animals and insects. Analysis of the 2,167,301 bp genome of Bifidobacterium asteroides PRL2011, a strain isolated from the hindgut of Apis mellifera var. ligustica, commonly known as the honey bee, revealed its predicted capability for respiratory metabolism. Conservation of the latter gene clusters in various B. asteroides strains enforces the notion that respiration is a common metabolic feature of this ancient bifidobacterial species, which has been lost in currently known mammal-derived Bifidobacterium species. In fact, phylogenomic based analyses suggested an ancient origin of B. asteroides and indicates it as an ancestor of the genus Bifidobacterium. Furthermore, the B. asteroides PRL2011 genome encodes various enzymes for coping with toxic products that arise as a result of oxygen-mediated respiration. PMID:23028506

  11. Global analysis of asymmetric RNA enrichment in oocytes reveals low conservation between closely related Xenopus species

    PubMed Central

    Claußen, Maike; Lingner, Thomas; Pommerenke, Claudia; Opitz, Lennart; Salinas, Gabriela; Pieler, Tomas

    2015-01-01

    RNAs that localize to the vegetal cortex during Xenopus laevis oogenesis have been reported to function in germ layer patterning, axis determination, and development of the primordial germ cells. Here we report on the genome-wide, comparative analysis of differentially localizing RNAs in Xenopus laevis and Xenopus tropicalis oocytes, revealing a surprisingly weak degree of conservation in respect to the identity of animally as well as vegetally enriched transcripts in these closely related species. Heterologous RNA injections and protein binding studies indicate that the different RNA localization patterns in these two species are due to gain/loss of cis-acting localization signals rather than to differences in the RNA-localizing machinery. PMID:26337391

  12. Ancient mitochondrial DNA analysis reveals complexity of indigenous North American turkey domestication

    PubMed Central

    Speller, Camilla F.; Kemp, Brian M.; Wyatt, Scott D.; Monroe, Cara; Lipe, William D.; Arndt, Ursula M.; Yang, Dongya Y.

    2010-01-01

    Although the cultural and nutritive importance of the turkey (Meleagris gallopavo) to precontact Native Americans and contemporary people worldwide is clear, little is known about the domestication of this bird compared to other domesticates. Mitochondrial DNA analysis of 149 turkey bones and 29 coprolites from 38 archaeological sites (200 BC–AD 1800) reveals a unique domesticated breed in the precontact Southwestern United States. Phylogeographic analyses indicate that this domestic breed originated from outside the region, but rules out the South Mexican domestic turkey (Meleagris gallopavo gallopavo) as a progenitor. A strong genetic bottleneck within the Southwest turkeys also reflects intensive human selection and breeding. This study points to at least two occurrences of turkey domestication in precontact North America and illuminates the intensity and sophistication of New World animal breeding practices. PMID:20133614

  13. Genome Wide Analysis of Chromatin Regulation by Cocaine Reveals a Novel Role for Sirtuins

    PubMed Central

    Renthal, William; Kumar, Arvind; Xiao, Guanghua; Wilkinson, Matthew; Covington, Herbert E.; Maze, Ian; Sikder, Devanjan; Robison, Alfred J.; LaPlant, Quincey; Dietz, David M.; Russo, Scott J.; Vialou, Vincent; Chakravarty, Sumana; Kodadek, Thomas J.; Stack, Ashley; Kabbaj, Mohammed; Nestler, Eric J.

    2009-01-01

    Summary Changes in gene expression contribute to the long-lasting regulation of the brain’s reward circuitry seen in drug addiction, however, the specific genes regulated and the transcriptional mechanisms underlying such regulation remain poorly understood. Here, we used chromatin immunoprecipitation coupled with promoter microarray analysis to characterize genome-wide chromatin changes in the mouse nucleus accumbens, a crucial brain reward region, after repeated cocaine administration. Our findings reveal several interesting principles of gene regulation by cocaine and of the role of ΔFosB and CREB, two prominent cocaine-induced transcription factors, in this brain region. The findings also provide novel and comprehensive insight into the molecular pathways regulated by cocaine – including a new role for sirtuins (Sirt1 and Sirt2) –which are induced in the nucleus accumbens by cocaine and, in turn, dramatically enhance the behavioral effects of the drug. PMID:19447090

  14. Evaluating the effects of variation in clinical practice: a risk adjusted cost-effectiveness (RAC-E) analysis of acute stroke services

    PubMed Central

    2012-01-01

    Background Methods for the cost-effectiveness analysis of health technologies are now well established, but such methods may also have a useful role in the context of evaluating the effects of variation in applied clinical practice. This study illustrates a general methodology for the comparative analysis of applied clinical practice at alternative institutions – risk adjusted cost-effectiveness (RAC-E) analysis – with an application that compares acute hospital services for stroke patients admitted to the main public hospitals in South Australia. Methods Using linked, routinely collected data on all South Australian hospital separations from July 2001 to June 2008, an analysis of the RAC-E of services provided at four metropolitan hospitals was undertaken using a decision analytic framework. Observed (plus extrapolated) and expected lifetime costs and survival were compared across patient populations, from which the relative cost-effectiveness of services provided at the different hospitals was estimated. Results Unadjusted results showed that at one hospital patients incurred fewer costs and gained more life years than at the other hospitals (i.e. it was the dominant hospital). After risk adjustment, the cost minimizing hospital incurred the lowest costs, but with fewer life-years gained than one other hospital. The mean incremental cost per life-year gained of services provided at the most effective hospital was under $20,000, with an associated 65% probability of being cost-effective at a $50,000 per life year monetary threshold. Conclusions RAC-E analyses can be used to identify important variation in the costs and outcomes associated with clinical practice at alternative institutions. Such data provides an impetus for further investigation to identify specific areas of variation, which may then inform the dissemination of best practice service delivery and organisation. PMID:22905669

  15. Cluster analysis reveals a binary effect of storage on boar sperm motility function.

    PubMed

    Henning, Heiko; Petrunkina, Anna M; Harrison, Robin A P; Waberski, Dagmar

    2014-06-01

    Storage of liquid-preserved boar spermatozoa is associated with a loss of fertilising ability of the preserved spermatozoa, which standard semen parameters barely reflect. Monitoring responses to molecular effectors of sperm function (e.g. bicarbonate) has proven to be a more sensitive approach to investigating storage effects. Bicarbonate not only initiates capacitation in spermatozoa, but also induces motility activation. This occurs at ejaculation, but also happens throughout passage through the oviduct. In the present study we tested whether the specific response of boar sperm subpopulations to bicarbonate, as assessed by motility activation, is altered with the duration of storage in vitro. Three ejaculates from each of seven boars were diluted in Beltsville thawing solution and stored at 17°C. Only minor changes in the parameters of diluted semen were revealed over a period of 72h storage. For assessment of bicarbonate responses, subsamples of diluted spermatozoa were centrifuged through a discontinuous Percoll gradient after 12, 24 and 72h storage. Subsequently, spermatozoa were incubated in two Ca2+-free variants of Tyrode's medium either without (TyrControl) or with (TyrBic) 15mM bicarbonate, and computer-aided sperm analysis motility measurements were made. Cluster analysis of imaging data from motile spermatozoa revealed the presence of five major sperm subpopulations with distinct motility characteristics, differing between TyrBic and TyrControl at any given time (P<0.001). Although there was an increasing loss of motility function in both media, bicarbonate induced an increase in a 'fast linear' cohort of spermatozoa in TyrBic regardless of storage (66.4% at 12h and 63.9% at 72h). These results imply a binary pattern in response of sperm motility function descriptors to storage: although the quantitative descriptor (percentage of motile spermatozoa) declines in washed semen samples, the qualitative descriptor (percentage of spermatozoa stimulated into

  16. Comparative Genomic Analysis of the Endosymbionts of Herbivorous Insects Reveals Eco-Environmental Adaptations: Biotechnology Applications

    PubMed Central

    Shi, Weibing; Xie, Shangxian; Chen, Xueyan; Sun, Su; Zhou, Xin; Liu, Lantao; Gao, Peng; Kyrpides, Nikos C.; No, En-Gyu; Yuan, Joshua S.

    2013-01-01

    Metagenome analysis of the gut symbionts of three different insects was conducted as a means of comparing taxonomic and metabolic diversity of gut microbiomes to diet and life history of the insect hosts. A second goal was the discovery of novel biocatalysts for biorefinery applications. Grasshopper and cutworm gut symbionts were sequenced and compared with the previously identified metagenome of termite gut microbiota. These insect hosts represent three different insect orders and specialize on different food types. The comparative analysis revealed dramatic differences among the three insect species in the abundance and taxonomic composition of the symbiont populations present in the gut. The composition and abundance of symbionts was correlated with their previously identified capacity to degrade and utilize the different types of food consumed by their hosts. The metabolic reconstruction revealed that the gut metabolome of cutworms and grasshoppers was more enriched for genes involved in carbohydrate metabolism and transport than wood-feeding termite, whereas the termite gut metabolome was enriched for glycosyl hydrolase (GH) enzymes relevant to lignocellulosic biomass degradation. Moreover, termite gut metabolome was more enriched with nitrogen fixation genes than those of grasshopper and cutworm gut, presumably due to the termite's adaptation to the high fiber and less nutritious food types. In order to evaluate and exploit the insect symbionts for biotechnology applications, we cloned and further characterized four biomass-degrading enzymes including one endoglucanase and one xylanase from both the grasshopper and cutworm gut symbionts. The results indicated that the grasshopper symbiont enzymes were generally more efficient in biomass degradation than the homologous enzymes from cutworm symbionts. Together, these results demonstrated a correlation between the composition and putative metabolic functionality of the gut microbiome and host diet, and suggested

  17. Differentially expressed genes and interacting pathways in bladder cancer revealed by bioinformatic analysis.

    PubMed

    Shen, Yinzhou; Wang, Xuelei; Jin, Yongchao; Lu, Jiasun; Qiu, Guangming; Wen, Xiaofei

    2014-10-01

    The goal of this study was to identify cancer-associated differentially expressed genes (DEGs), analyze their biological functions and investigate the mechanism(s) of cancer occurrence and development, which may provide a theoretical foundation for bladder cancer (BCa) therapy. We downloaded the mRNA expression profiling dataset GSE13507 from the Gene Expression Omnibus database; the dataset includes 165 BCa and 68 control samples. T‑tests were used to identify DEGs. To further study the biological functions of the identified DEGs, we performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Next, we built a network of potentially interacting pathways to study the synergistic relationships among DEGs. A total of 12,105 genes were identified as DEGs, of which 5,239 were upregulated and 6,866 were downregulated in BCa. The DEGs encoding activator protein 1 (AP-1), nuclear factor of activated T-cells (NFAT) proteins, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and interleukin (IL)-10 were revealed to participate in the significantly enriched immune pathways that were downregulated in BCa. KEGG enrichment analysis revealed 7 significantly upregulated and 47 significantly downregulated pathways enriched among the DEGs. We found a crosstalk interaction among a total of 44 pathways in the network of BCa-affected pathways. In conclusion, our results show that BCa involves dysfunctions in multiple systems. Our study is expected to pave ways for immune and inflammatory research and provide molecular insights for cancer therapy.

  18. Wavelet Analysis of DNA Bending Profiles reveals Structural Constraints on the Evolution of Genomic Sequences.

    PubMed

    Audit, Benjamin; Vaillant, Cédric; Arnéodo, Alain; d'Aubenton-Carafa, Yves; Thermes, Claude

    2004-03-01

    Analyses of genomic DNA sequences have shown in previous works that base pairs are correlated at large distances with scale-invariant statistical properties. We show in the present study that these correlations between nucleotides (letters) result in fact from long-range correlations (LRC) between sequence-dependent DNA structural elements (words) involved in the packaging of DNA in chromatin. Using the wavelet transform technique, we perform a comparative analysis of the DNA text and of the corresponding bending profiles generated with curvature tables based on nucleosome positioning data. This exploration through the optics of the so-called `wavelet transform microscope' reveals a characteristic scale of 100-200 bp that separates two regimes of different LRC. We focus here on the existence of LRC in the small-scale regime (≲ 200 bp). Analysis of genomes in the three kingdoms reveals that this regime is specifically associated to the presence of nucleosomes. Indeed, small scale LRC are observed in eukaryotic genomes and to a less extent in archaeal genomes, in contrast with their absence in eubacterial genomes. Similarly, this regime is observed in eukaryotic but not in bacterial viral DNA genomes. There is one exception for genomes of Poxviruses, the only animal DNA viruses that do not replicate in the cell nucleus and do not present small scale LRC. Furthermore, no small scale LRC are detected in the genomes of all examined RNA viruses, with one exception in the case of retroviruses. Altogether, these results strongly suggest that small-scale LRC are a signature of the nucleosomal structure. Finally, we discuss possible interpretations of these small-scale LRC in terms of the mechanisms that govern the positioning, the stability and the dynamics of the nucleosomes along the DNA chain. This paper is maily devoted to a pedagogical presentation of the theoretical concepts and physical methods which are well suited to perform a statistical analysis of genomic

  19. The diversity of algal phospholipase D homologs revealed by biocomputational analysis.

    PubMed

    Beligni, María Verónica; Bagnato, Carolina; Prados, María Belén; Bondino, Hernán; Laxalt, Ana María; Munnik, Teun; Ten Have, Arjen

    2015-10-01

    Phospholipase D (PLD) participates in the formation of phosphatidic acid, a precursor in glycerolipid biosynthesis and a second messenger. PLDs are part of a superfamily of proteins that hydrolyze phosphodiesters and share a catalytic motif, HxKxxxxD, and hence a mechanism of action. Although HKD-PLDs have been thoroughly characterized in plants, animals and bacteria, very little is known about these enzymes in algae. To fill this gap in knowledge, we performed a biocomputational analysis by means of HMMER iterative profiling, using most eukaryotic algae genomes available. Phylogenetic analysis revealed that algae exhibit very few eukaryotic-type PLDs but possess, instead, many bacteria-like PLDs. Among algae eukaryotic-type PLDs, we identified C2-PLDs and PXPH-like PLDs. In addition, the dinoflagellate Alexandrium tamarense features several proteins phylogenetically related to oomycete PLDs. Our phylogenetic analysis also showed that algae bacteria-like PLDs (proteins with putative PLD activity) fall into five clades, three of which are novel lineages in eukaryotes, composed almost entirely of algae. Specifically, Clade II is almost exclusive to diatoms, whereas Clade I and IV are mainly represented by proteins from prasinophytes. The other two clades are composed of mitochondrial PLDs (Clade V or Mito-PLDs), previously found in mammals, and a subfamily of potentially secreted proteins (Clade III or SP-PLDs), which includes a homolog formerly characterized in rice. In addition, our phylogenetic analysis shows that algae have non-PLD members within the bacteria-like HKD superfamily with putative cardiolipin synthase and phosphatidylserine/phosphatidylglycerophosphate synthase activities. Altogether, our results show that eukaryotic algae possess a moderate number of PLDs that belong to very diverse phylogenetic groups.

  20. Comparative transcriptomic analysis reveals similarities and dissimilarities in Saccharomyces cerevisiae wine strains response to nitrogen availability.

    PubMed

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12 h, 24 h and 96 h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12 h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the

  1. Comparative Transcriptomic Analysis Reveals Similarities and Dissimilarities in Saccharomyces cerevisiae Wine Strains Response to Nitrogen Availability

    PubMed Central

    Barbosa, Catarina; García-Martínez, José; Pérez-Ortín, José E.; Mendes-Ferreira, Ana

    2015-01-01

    Nitrogen levels in grape-juices are of major importance in winemaking ensuring adequate yeast growth and fermentation performance. Here we used a comparative transcriptome analysis to uncover wine yeasts responses to nitrogen availability during fermentation. Gene expression was assessed in three genetically and phenotypically divergent commercial wine strains (CEG, VL1 and QA23), under low (67 mg/L) and high nitrogen (670 mg/L) regimes, at three time points during fermentation (12h, 24h and 96h). Two-way ANOVA analysis of each fermentation condition led to the identification of genes whose expression was dependent on strain, fermentation stage and on the interaction of both factors. The high fermenter yeast strain QA23 was more clearly distinct from the other two strains, by differential expression of genes involved in flocculation, mitochondrial functions, energy generation and protein folding and stabilization. For all strains, higher transcriptional variability due to fermentation stage was seen in the high nitrogen fermentations. A positive correlation between maximum fermentation rate and the expression of genes involved in stress response was observed. The finding of common genes correlated with both fermentation activity and nitrogen up-take underlies the role of nitrogen on yeast fermentative fitness. The comparative analysis of genes differentially expressed between both fermentation conditions at 12h, where the main difference was the level of nitrogen available, showed the highest variability amongst strains revealing strain-specific responses. Nevertheless, we were able to identify a small set of genes whose expression profiles can quantitatively assess the common response of the yeast strains to varying nitrogen conditions. The use of three contrasting yeast strains in gene expression analysis prompts the identification of more reliable, accurate and reproducible biomarkers that will facilitate the diagnosis of deficiency of this nutrient in the grape

  2. Analysis of the Status Quo and Suggested Policy Adjustments for Sino-Foreign Cooperation in Running Schools

    ERIC Educational Resources Information Center

    Meiqiong, Qin

    2009-01-01

    Statistics and analysis indicate that there are many problems to be resolved over the issue of Sino-foreign cooperation in running schools. These include national policy failing to catch up with development, Chinese and foreign partners disagreeing on the objectives of their cosponsored programs, cooperation being geographically unbalanced,…

  3. Family Adjustment Measure: Scale Construction and Validation

    ERIC Educational Resources Information Center

    Daire, Andrew P.; Dominguez, Vanessa N.; Carlson, Ryan G.; Case-Pease, Jenene

    2014-01-01

    We administered the Family Adjustment Measure to 368 parents of children with special needs to identify positive adjustment. We randomly split the sample to conduct exploratory factor analysis ("n" = 194) and confirmatory factor analysis ("n" = 174). Results indicated four possible subscales and that explain 51% of the variance.

  4. Analysis of wheat SAGE tags reveals evidence for widespread antisense transcription

    PubMed Central

    Poole, Rebecca L; Barker, Gary LA; Werner, Kay; Biggi, Gaia F; Coghill, Jane; Gibbings, J George; Berry, Simon; Dunwell, Jim M; Edwards, Keith J

    2008-01-01

    gene expression. Conclusion Our results indicate that the detailed analysis of transcriptome data, such as SAGE tags, is essential to understand fully the factors that regulate gene expression and that such analysis of the wheat grain transcriptome reveals that antisense transcripts maybe widespread and hence probably play a significant role in the regulation of gene expression during grain development. PMID:18847483

  5. Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays.

    PubMed

    Galati, Domenico F; Abuin, David S; Tauber, Gabriel A; Pham, Andrew T; Pearson, Chad G

    2015-12-23

    Multi-ciliated cells (MCCs) use polarized fields of undulating cilia (ciliary array) to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs) that are arranged within a spatially complex 3-dimensional geometry (3D). Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs.

  6. Singularity analysis of the AKT signaling pathway reveals connections between cancer and metabolic diseases

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu

    2010-12-01

    Connections between cancer and metabolic diseases may consist in the complex network of interactions among a common set of biomolecules. By applying singularity and bifurcation analysis, the phenotypes constrained by the AKT signaling pathway are identified and mapped onto the parameter space, which include cancer and certain metabolic diseases. By considering physiologic properties (sensitivity, robustness and adaptivity) the AKT pathway must possess in order to efficiently sense growth factors and nutrients, the region of normal responses is located. To optimize these properties, the intracellular concentration of the AKT protein must be sufficiently high to saturate its enzymes; the strength of the positive feedback must be stronger than that of the negative feedback. The analysis illuminates the parameter space and reveals system-level mechanisms in regulating biological functions (cell growth, survival, proliferation and metabolism) and how their deregulation may lead to the development of diseases. The analytical expressions summarize the synergistic interactions among many molecules, which provides valuable insights into therapeutic interventions. In particular, a strategy for overcoming the limitations of mTOR inhibition is proposed for cancer therapy.

  7. Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production

    PubMed Central

    Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

    2015-01-01

    Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production. PMID:26348427

  8. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions

    NASA Astrophysics Data System (ADS)

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I.; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B. H.

    2016-05-01

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions.

  9. Comparative Transcriptome Analysis Reveals Different Silk Yields of Two Silkworm Strains

    PubMed Central

    Li, Juan; Qin, Sheng; Yu, Huanjun; Zhang, Jing; Liu, Na; Yu, Ye; Hou, Chengxiang; Li, Muwang

    2016-01-01

    Cocoon and silk yields are the most important characteristics of sericulture. However, few studies have examined the genes that modulate these features. Further studies of these genes will be useful for improving the products of sericulture. JingSong (JS) and Lan10 (L10) are two strains having significantly different cocoon and silk yields. In the current study, RNA-Seq and quantitative polymerase chain reaction (qPCR) were performed on both strains in order to determine divergence of the silk gland, which controls silk biosynthesis in silkworms. Compared with L10, JS had 1375 differentially expressed genes (DEGs; 738 up-regulated genes and 673 down-regulated genes). Nine enriched gene ontology (GO) terms were identified by GO enrichment analysis based on these DEGs. KEGG enrichment analysis results showed that the DEGs were enriched in three pathways, which were mainly associated with the processing and biosynthesis of proteins. The representative genes in the enrichment pathways and ten significant DEGs were further verified by qPCR, the results of which were consistent with the RNA-Seq data. Our study has revealed differences in silk glands between the two silkworm strains and provides a perspective for understanding the molecular mechanisms determining silk yield. PMID:27159277

  10. Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis

    PubMed Central

    Gu, Jinping; Hu, Xiaomin; Shao, Wei; Ji, Tianhai; Yang, Wensheng; Zhuo, Huiqin; Jin, Zeyu; Huang, Huiying; Chen, Jiacheng; Huang, Caihua; Lin, Donghai

    2016-01-01

    Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression. PMID:27527852

  11. Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability.

    PubMed

    Li, Jia; Liu, Fei; Wang, Qi; Ge, Pupu; Woo, Patrick C Y; Yan, Jinghua; Zhao, Yanlin; Gao, George F; Liu, Cui Hua; Liu, Changting

    2014-08-28

    The emergence and rapid spread of New Delhi Metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae strains has caused a great concern worldwide. To better understand the mechanisms underlying environmental adaptation of those highly drug-resistant K. pneumoniae strains, we took advantage of the China's Shenzhou 10 spacecraft mission to conduct comparative genomic and transcriptomic analysis of a NDM-1 K. pneumoniae strain (ATCC BAA-2146) being cultivated under different conditions. The samples were recovered from semisolid medium placed on the ground (D strain), in simulated space condition (M strain), or in Shenzhou 10 spacecraft (T strain) for analysis. Our data revealed multiple variations underlying pathogen adaptation into different environments in terms of changes in morphology, H2O2 tolerance and biofilm formation ability, genomic stability and regulation of metabolic pathways. Additionally, we found a few non-coding RNAs to be differentially regulated. The results are helpful for better understanding the adaptive mechanisms of drug-resistant bacterial pathogens.

  12. Proteomic Analysis of a Novel Bacillus Jumbo Phage Revealing Glycoside Hydrolase As Structural Component

    PubMed Central

    Yuan, Yihui; Gao, Meiying

    2016-01-01

    Tailed phages with genomes of larger than 200 kbp are classified as Jumbo phages and exhibited extremely high uncharted diversity. The genomic annotation of Jumbo phage is often disappointing because most of the predicted proteins, including structural proteins, failed to make good hits to the sequences in the databases. In this study, 23 proteins of a novel Bacillus Jumbo phage, vB_BpuM_BpSp, were identified as phage structural proteins by the structural proteome analysis, including 14 proteins of unknown function, 5 proteins with predicted function as structural proteins, a glycoside hydrolase, a Holliday junction resolvase, a RNA-polymerase β-subunit, and a host-coding portal protein, which might be hijacked from the host strain during phage virion assembly. The glycoside hydrolase (Gp255) was identified as phage virion component and was found to interact with the phage baseplate protein. Gp255 shows specific lytic activity against the phage host strain GR8 and has high temperature tolerance. In situ peptidoglycan-hydrolyzing activities analysis revealed that the expressed Gp255 and phage structural proteome exhibited glycoside hydrolysis activity against the tested GR8 cell extracts. This study identified the first functional individual structural glycoside hydrolase in phage virion. The presence of activated glycoside hydrolase in phage virions might facilitate the injection of the phage genome during infection by forming pores on the bacterial cell wall. PMID:27242758

  13. Functional analysis reveals that RBM10 mutations contribute to lung adenocarcinoma pathogenesis by deregulating splicing

    PubMed Central

    Zhao, Jiawei; Sun, Yue; Huang, Yin; Song, Fan; Huang, Zengshu; Bao, Yufang; Zuo, Ji; Saffen, David; Shao, Zhen; Liu, Wen; Wang, Yongbo

    2017-01-01

    RBM10 is an RNA splicing regulator that is frequently mutated in lung adenocarcinoma (LUAD) and has recently been proposed to be a cancer gene. How RBM10 mutations observed in LUAD affect its normal functions, however, remains largely unknown. Here integrative analysis of RBM10 mutation and RNA expression data revealed that LUAD-associated RBM10 mutations exhibit a mutational spectrum similar to that of tumor suppressor genes. In addition, this analysis showed that RBM10 mutations identified in LUAD patients lacking canonical oncogenes are associated with significantly reduced RBM10 expression. To systematically investigate RBM10 mutations, we developed an experimental pipeline for elucidating their functional effects. Among six representative LUAD-associated RBM10 mutations, one nonsense and one frameshift mutation caused loss-of-function as expected, whereas four missense mutations differentially affected RBM10-mediated splicing. Importantly, changes in proliferation rates of LUAD-derived cells caused by these RBM10 missense mutants correlated with alterations in RNA splicing of RBM10 target genes. Together, our data implies that RBM10 mutations contribute to LUAD pathogenesis, at least in large part, by deregulating splicing. The methods described in this study should be useful for analyzing mutations in additional cancer-associated RNA splicing regulators. PMID:28091594

  14. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres

    PubMed Central

    Wu, Dan; Kendrick, Keith M.; Levitin, Daniel J.; Li, Chaoyi; Yao, Dezhong

    2015-01-01

    Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach’s harmony patterns were having the most influence on those used by other composers, followed closely by Mozart. PMID:26545104

  15. Comparative analysis and functional mapping of SACS mutations reveal novel insights into sacsin repeated architecture.

    PubMed

    Romano, Alessandro; Tessa, Alessandra; Barca, Amilcare; Fattori, Fabiana; de Leva, Maria Fulvia; Terracciano, Alessandra; Storelli, Carlo; Santorelli, Filippo Maria; Verri, Tiziano

    2013-03-01

    Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a neurological disease with mutations in SACS, encoding sacsin, a multidomain protein of 4,579 amino acids. The large size of SACS and its translated protein has hindered biochemical analysis of ARSACS, and how mutant sacsins lead to disease remains largely unknown. Three repeated sequences, called sacsin repeating region (SRR) supradomains, have been recognized, which contribute to sacsin chaperone-like activity. We found that the three SRRs are much larger (≥1,100 residues) than previously described, and organized in discrete subrepeats. We named the large repeated regions Sacsin Internal RePeaTs (SIRPT1, SIRPT2, and SIRPT3) and the subrepeats sr1, sr2, sr3, and srX. Comparative analysis of vertebrate sacsins in combination with fine positional mapping of a set of human mutations revealed that sr1, sr2, sr3, and srX are functional. Notably, the position of the pathogenic mutations in sr1, sr2, sr3, and srX appeared to be related to the severity of the clinical phenotype, as assessed by defining a severity scoring system. Our results suggest that the relative position of mutations in subrepeats will variably influence sacsin dysfunction. The characterization of the specific role of each repeated region will help in developing a comprehensive and integrated pathophysiological model of function for sacsin.

  16. Metagenomic analysis reveals that bacteriophages are reservoirs of antibiotic resistance genes.

    PubMed

    Subirats, Jéssica; Sànchez-Melsió, Alexandre; Borrego, Carles M; Balcázar, José Luis; Simonet, Pascal

    2016-08-01

    A metagenomics approach was applied to explore the presence of antibiotic resistance genes (ARGs) in bacteriophages from hospital wastewater. Metagenomic analysis showed that most phage sequences affiliated to the order Caudovirales, comprising the tailed phage families Podoviridae, Siphoviridae and Myoviridae. Moreover, the relative abundance of ARGs in the phage DNA fraction (0.26%) was higher than in the bacterial DNA fraction (0.18%). These differences were particularly evident for genes encoding ATP-binding cassette (ABC) and resistance-nodulation-cell division (RND) proteins, phosphotransferases, β-lactamases and plasmid-mediated quinolone resistance. Analysis of assembled contigs also revealed that blaOXA-10, blaOXA-58 and blaOXA-24 genes belonging to class D β-lactamases as well as a novel blaTEM (98.9% sequence similarity to the blaTEM-1 gene) belonging to class A β-lactamases were detected in a higher proportion in phage DNA. Although preliminary, these findings corroborate the role of bacteriophages as reservoirs of resistance genes and thus highlight the necessity to include them in future studies on the emergence and spread of antibiotic resistance in the environment.

  17. Comparative Transcriptome Analysis Reveals Early Pregnancy-Specific Genes Expressed in Peripheral Blood of Pregnant Sows

    PubMed Central

    Zhu, Shien; Shi, Wenqing; Hu, Maishun; Fu, Xiangwei; Wang, Chuduan; Wang, Yachun; Zhang, Qin; Yu, Ying

    2014-01-01

    Early and accurate diagnosis of pregnancy is important for effective management of an economical pig farm. Besides the currently available methods used in early diagnosis of sows, circulating nucleic acids in peripheral blood may contain some early pregnancy-specific molecular markers. For the first time, microarray analysis of peripheral blood from pregnant sows versus non-pregnant sows identified 127 up-regulated and 56 down-regulated genes at day 14 post-insemination. Gene Ontology annotation grouped the total differently expressed genes into 3 significantly enriched terms, cell surface receptor linked signal transduction, G-protein coupled receptor protein signaling pathway and regulation of vesicle-mediated transport. Signaling pathway analysis revealed the only one significantly changed pathway was arachidonic acid metabolism. Of the differently expressed genes, nine (including LPAR3, RXFP4, GALP, CBR1, CBR2, GPX6, USP18, LHB and NR5A1) were found to exert function related to early pregnancy processes. This study provides a clue that differentially abundant RNAs in maternal peripheral blood can help to identify the molecular markers of early pregnancy in pigs. PMID:25479131

  18. Transcriptome analysis reveals long noncoding RNAs involved in fiber development in cotton (Gossypium arboreum).

    PubMed

    Zou, Changsong; Wang, Qiaolian; Lu, Cairui; Yang, Wencui; Zhang, Youping; Cheng, Hailiang; Feng, Xiaoxu; Prosper, Mtawa Andrew; Song, Guoli

    2016-02-01

    Long noncoding RNAs (lncRNAs) play important roles in various biological regulatory processes in yeast, mammals, and plants. However, no systematic identification of lncRNAs has been reported in Gossypium arboreum. In this study, the strand-specific RNA sequencing (ssRNA-seq) of samples from cotton fibers and leaves was performed, and lncRNAs involved in fiber initiation and elongation processes were systematically identified and analyzed. We identified 5,996 lncRNAs, of which 3,510 and 2,486 can be classified as long intergenic noncoding RNAs (lincRNAs) and natural antisense transcripts (lncNAT), respectively. LincRNAs and lncNATs are similar in many aspects, but have some differences in exon number, exon length, and transcript length. Expression analysis revealed that 51.9% of lincRNAs and 54.5% of lncNATs transcripts were preferentially expressed at one stage of fiber development, and were significantly highly expressed than protein-coding transcripts (21.7%). During the fiber and rapid elongation stages, rapid and dynamic changes in lncRNAs may contribute to fiber development in cotton. This work describes a set of lncRNAs that are involved in fiber development. The characterization and expression analysis of lncRNAs will facilitate future studies on their roles in fiber development in cotton.

  19. Multifractal analysis of Barkhausen noise reveals the dynamic nature of criticality at hysteresis loop

    NASA Astrophysics Data System (ADS)

    Tadić, Bosiljka

    2016-06-01

    The field-driven magnetisation reversal processes in disordered systems exhibit a collective behaviour that is manifested in the scale-invariance of avalanches, closely related to underlying dynamical mechanisms. Using the multifractal time series analysis, we study the structure of fluctuations at different scales in the accompanying Barkhausen noise. The stochastic signal represents the magnetisation discontinuities along the hysteresis loop of a three-dimensional random field Ising model simulated for varied disorder strength and driving rates. The analysis of the spectrum of the generalised Hurst exponents reveals that the dominant segments of the signal with large fluctuations represent two distinct classes of stochastic processes in weak and strong pinning regimes. Furthermore, in the weak pinning regime, the part of the signal originating from the beginning of the hysteresis loop has a different multifractal spectrum than the signal near the coercive field. The enhanced fluctuations (primarily in the central part of the hysteresis loop) for increased driving rate and larger system size, lead to a further broadening of the spectrum. The analysed Barkhausen signals are also shown to exhibit temporal correlations and power-law distributions of the magnetisation discontinuity and avalanche sizes, in agreement with previous studies. The multifractal properties of Barkhausen noise describe the dynamical state of domains and precisely discriminate the weak pinning, permitting the motion of individual walls, from the mechanisms occurring in strongly disordered systems.

  20. Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese

    PubMed Central

    Tang, Clara S.; Zhang, He; Cheung, Chloe Y. Y.; Xu, Ming; Ho, Jenny C. Y.; Zhou, Wei; Cherny, Stacey S.; Zhang, Yan; Holmen, Oddgeir; Au, Ka-Wing; Yu, Haiyi; Xu, Lin; Jia, Jia; Porsch, Robert M.; Sun, Lijie; Xu, Weixian; Zheng, Huiping; Wong, Lai-Yung; Mu, Yiming; Dou, Jingtao; Fong, Carol H. Y.; Wang, Shuyu; Hong, Xueyu; Dong, Liguang; Liao, Yanhua; Wang, Jiansong; Lam, Levina S. M.; Su, Xi; Yan, Hua; Yang, Min-Lee; Chen, Jin; Siu, Chung-Wah; Xie, Gaoqiang; Woo, Yu-Cho; Wu, Yangfeng; Tan, Kathryn C. B.; Hveem, Kristian; Cheung, Bernard M. Y.; Zöllner, Sebastian; Xu, Aimin; Eugene Chen, Y; Jiang, Chao Qiang; Zhang, Youyi; Lam, Tai-Hing; Ganesh, Santhi K.; Huo, Yong; Sham, Pak C.; Lam, Karen S. L.; Willer, Cristen J.; Tse, Hung-Fat; Gao, Wei

    2015-01-01

    Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10−7), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci—PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser—also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD. PMID:26690388

  1. Time-series analysis reveals genetic responses to intensive management of razorback sucker (Xyrauchen texanus)

    PubMed Central

    Dowling, Thomas E; Turner, Thomas F; Carson, Evan W; Saltzgiver, Melody J; Adams, Deborah; Kesner, Brian; Marsh, Paul C

    2014-01-01

    Time-series analysis is used widely in ecology to study complex phenomena and may have considerable potential to clarify relationships of genetic and demographic processes in natural and exploited populations. We explored the utility of this approach to evaluate population responses to management in razorback sucker, a long-lived and fecund, but declining freshwater fish species. A core population in Lake Mohave (Arizona-Nevada, USA) has experienced no natural recruitment for decades and is maintained by harvesting naturally produced larvae from the lake, rearing them in protective custody, and repatriating them at sizes less vulnerable to predation. Analyses of mtDNA and 15 microsatellites characterized for sequential larval cohorts collected over a 15-year time series revealed no changes in geographic structuring but indicated significant increase in mtDNA diversity for the entire population over time. Likewise, ratios of annual effective breeders to annual census size (Nb/Na) increased significantly despite sevenfold reduction of Na. These results indicated that conservation actions diminished near-term extinction risk due to genetic factors and should now focus on increasing numbers of fish in Lake Mohave to ameliorate longer-term risks. More generally, time-series analysis permitted robust testing of trends in genetic diversity, despite low precision of some metrics. PMID:24665337

  2. Automated image analysis reveals the dynamic 3-dimensional organization of multi-ciliary arrays

    PubMed Central

    Galati, Domenico F.; Abuin, David S.; Tauber, Gabriel A.; Pham, Andrew T.; Pearson, Chad G.

    2016-01-01

    ABSTRACT Multi-ciliated cells (MCCs) use polarized fields of undulating cilia (ciliary array) to produce fluid flow that is essential for many biological processes. Cilia are positioned by microtubule scaffolds called basal bodies (BBs) that are arranged within a spatially complex 3-dimensional geometry (3D). Here, we develop a robust and automated computational image analysis routine to quantify 3D BB organization in the ciliate, Tetrahymena thermophila. Using this routine, we generate the first morphologically constrained 3D reconstructions of Tetrahymena cells and elucidate rules that govern the kinetics of MCC organization. We demonstrate the interplay between BB duplication and cell size expansion through the cell cycle. In mutant cells, we identify a potential BB surveillance mechanism that balances large gaps in BB spacing by increasing the frequency of closely spaced BBs in other regions of the cell. Finally, by taking advantage of a mutant predisposed to BB disorganization, we locate the spatial domains that are most prone to disorganization by environmental stimuli. Collectively, our analyses reveal the importance of quantitative image analysis to understand the principles that guide the 3D organization of MCCs. PMID:26700722

  3. Network analysis reveals common host protein/s modulating pathogenesis of neurotropic viruses

    PubMed Central

    Ghosh, Sourish; Mukherjee, Sriparna; Sengupta, Nabonita; Roy, Arunava; Dey, Dhritiman; Chakraborty, Surajit; Chattopadhyay, Dhrubajyoti; Banerjee, Arpan; Basu, Anirban

    2016-01-01

    Network analysis through graph theory provides a quantitative approach to characterize specific proteins and their constituent assemblies that underlie host-pathogen interactions. In the present study, graph theory was used to analyze the interactome designed out of 50 differentially expressing proteins from proteomic analysis of Chandipura Virus (CHPV, Family: Rhabdoviridae) infected mouse brain tissue to identify the primary candidates for intervention. Using the measure of degree centrality, that quantifies the connectedness of a single protein within a milieu of several other interacting proteins, DJ-1 was selected for further molecular validation. To elucidate the generality of DJ-1’s role in propagating infection its role was also monitored in another RNA virus, Japanese Encephalitis Virus (JEV, Family: Flaviviridae) infection. Concurrently, DJ-1 got over-expressed in response to reactive oxygen species (ROS) generation following viral infection which in the early phase of infection migrated to mitochondria to remove dysfunctional mitochondria through the process of mitophagy. DJ-1 was also observed to modulate the viral replication and interferon responses along with low-density lipoprotein (LDL) receptor expression in neurons. Collectively these evidences reveal a comprehensive role for DJ-1 in neurotropic virus infection in the brain. PMID:27581498

  4. Systematic proteomic analysis of human hepotacellular carcinoma cells reveals molecular pathways and networks involved in metastasis.

    PubMed

    Yu, Yanyan; Shen, Huali; Yu, Hongxiu; Zhong, Fan; Zhang, Yang; Zhang, Chen; Zhao, Jian; Li, Hong; Chen, Jie; Liu, Yinkun; Yang, Pengyuan

    2011-06-01

    Systematic proteomic studying of the mechanism of hepatocellular carcinoma (HCC) metastasis remains challenging. We performed comparative proteomic and pathway analysis of four human metastatic HCC cell lines to identify metastasis-associated proteins. These HCC cell lines had a similar genetic background but with an increasing potential of metastasis. Using a combination of two dimensional electrophoresis (2-DE) and MALDI-TOF mass spectrometry, a total of 125 proteins and their post-translational modification forms or isoforms were found to be differentially expressed in the cell lines. Among them, 29 were gradually up-regulated whereas 17 were down-regulated with increasing metastatic potential. Instead of a traditional single-gene readout, global bioinformatics analysis was carried out, which revealed that the glycolysis pathway was the most significantly enriched pathway. The heat shock proteins (HSPs) centered and NF-kappaB centered networks were also enriched in the result, which may imply the key function of inflaming on metastasis. Meanwhile, knockdown of HDGF, an up-regulated protein and a target of NF-kappaB, induced cell apoptosis in the metastatic HCC cells. This work provides a demonstration that a combination of bioinformatics and comparative proteomics can help in finding out potential biomarkers associated with HCC metastasis on the level of pathways.

  5. The heterogeneity of meningioma revealed by multiparameter analysis: infiltrative and non-infiltrative clinical phenotypes.

    PubMed

    Gay, Emmanuel; Lages, Elodie; Ramus, Claire; Guttin, Audrey; El Atifi, Michèle; Dupré, Isabelle; Bouamrani, Ali; Salon, Caroline; Ratel, David; Wion, Didier; Berger, François; Issartel, Jean-Paul

    2011-05-01

    Tumor invasion or infiltration of adjacent tissues is the source of clinical challenges in diagnosis as well as prevention and treatment. Among brain tumors, infiltration of the adjacent tissues with diverse pleiotropic mechanisms is frequently encountered in benign meningiomas. We assessed whether a multiparametric analysis of meningiomas based on data from both clinical observations and molecular analyses could provide a consistent and accurate appraisal of invasive and infiltrative phenotypes and help determine the diagnosis of these tumors. Tissue analyses of 37 meningiomas combined enzyme-linked immunosorbent assay (ELISA) and surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) assays of two different protein biomarkers (thrombospondin 1 and a phosphorylated form of vimentin) as well as gene expression analyses with oligonucleotide micro-arrays. Up to four different clinical and molecular parameters were then examined for tumor classification. From this study, we were able to cluster 36 out of the 37 tumors into two different subsets corresponding to infiltrative/invasive and non-infiltrative tumors. In addition, meningiomas that invade brain and those that infiltrate the neighboring skull bone exhibited no distinguishable molecular features. Our multi-parameter analysis that combines clinical data, transcriptomic and molecular assays clearly reveals the heterogeneity of meningiomas and distinguishes the intrinsically infiltrative/invasive tumors from the non-infiltrative meningiomas.

  6. Genetic analysis reveals the wild ancestors of the llama and the alpaca.

    PubMed Central

    Kadwell, M.; Fernandez, M.; Stanley, H. F.; Baldi, R.; Wheeler, J. C.; Rosadio, R.; Bruford, M. W.

    2001-01-01

    The origins of South America's domestic alpaca and llama remain controversial due to hybridization, near extirpation during the Spanish conquest and difficulties in archaeological interpretation. Traditionally, the ancestry of both forms is attributed to the guanaco, while the vicuña is assumed never to have been domesticated. Recent research has, however, linked the alpaca to the vicuña, dating domestication to 6000-7000 years before present in the Peruvian Andes. Here, we examine in detail the genetic relationships between the South American camelids in order to determine the origins of the domestic forms, using mitochondrial (mt) and microsatellite DNA. MtDNA analysis places 80% of llama and alpaca sequences in the guanaco lineage, with those possessing vicuña mtDNA being nearly all alpaca or alpaca-vicuña hybrids. We also examined four microsatellites in wild known-provenance vicuña and guanaco, including two loci with non-overlapping allele size ranges in the wild species. In contrast to the mtDNA, these markers show high genetic similarity between alpaca and vicuña, and between llama and guanaco, although bidirectional hybridization is also revealed. Finally, combined marker analysis on a subset of samples confirms the microsatellite interpretation and suggests that the alpaca is descended from the vicuña, and should be reclassified as Vicugna pacos. This result has major implications for the future management of wild and domestic camelids in South America. PMID:11749713

  7. Spatial and temporal variation of total electron content as revealed by principal component analysis

    NASA Astrophysics Data System (ADS)

    Talaat, Elsayed R.; Zhu, Xun

    2016-11-01

    Eleven years of global total electron content (TEC) data derived from the assimilated thermosphere-ionosphere electrodynamics general circulation model are analyzed using empirical orthogonal function (EOF) decomposition and the corresponding principal component analysis (PCA) technique. For the daily averaged TEC field, the first EOF explains more than 89 % and the first four EOFs explain more than 98 % of the total variance of the TEC field, indicating an effective data compression and clear separation of different physical processes. The effectiveness of the PCA technique for TEC is nearly insensitive to the horizontal resolution and the length of the data records. When the PCA is applied to global TEC including local-time variations, the rich spatial and temporal variations of field can be represented by the first three EOFs that explain 88 % of the total variance. The spectral analysis of the time series of the EOF coefficients reveals how different mechanisms such as solar flux variation, change in the orbital declination, nonlinear mode coupling and geomagnetic activity are separated and expressed in different EOFs. This work demonstrates the usefulness of using the PCA technique to assimilate and monitor the global TEC field.

  8. Analysis of spatial-temporal gene expression patterns reveals dynamics and regionalization in developing mouse brain.

    PubMed

    Chou, Shen-Ju; Wang, Chindi; Sintupisut, Nardnisa; Niou, Zhen-Xian; Lin, Chih-Hsu; Li, Ker-Chau; Yeang, Chen-Hsiang

    2016-01-20

    Allen Brain Atlas (ABA) provides a valuable resource of spatial/temporal gene expressions in mammalian brains. Despite rich information extracted from this database, current analyses suffer from several limitations. First, most studies are either gene-centric or region-centric, thus are inadequate to capture the superposition of multiple spatial-temporal patterns. Second, standard tools of expression analysis such as matrix factorization can capture those patterns but do not explicitly incorporate spatial dependency. To overcome those limitations, we proposed a computational method to detect recurrent patterns in the spatial-temporal gene expression data of developing mouse brains. We demonstrated that regional distinction in brain development could be revealed by localized gene expression patterns. The patterns expressed in the forebrain, medullary and pontomedullary, and basal ganglia are enriched with genes involved in forebrain development, locomotory behavior, and dopamine metabolism respectively. In addition, the timing of global gene expression patterns reflects the general trends of molecular events in mouse brain development. Furthermore, we validated functional implications of the inferred patterns by showing genes sharing similar spatial-temporal expression patterns with Lhx2 exhibited differential expression in the embryonic forebrains of Lhx2 mutant mice. These analysis outcomes confirm the utility of recurrent expression patterns in studying brain development.

  9. Pre-2014 mudslides at Oso revealed by InSAR and multi-source DEM analysis

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Lu, Z.; QU, F.

    2014-12-01

    The landslide is a process that results in the downward and outward movement of slope-reshaping materials including rocks and soils and annually causes the loss of approximately $3.5 billion and tens of casualties in the United States. The 2014 Oso mudslide was an extreme event costing nearly 40 deaths and damaging civilian properties. Landslides are often unpredictable, but in many cases, catastrophic events are repetitive. Historic record in the Oso mudslide site indicates that there have been serial events in decades, though the extent of sliding events varied from time to time. In our study, the combination of multi-source DEMs, InSAR, and time-series InSAR analysis has enabled to characterize the Oso mudslide. InSAR results from ALOS PALSAR show that there was no significant deformation between mid-2006 and 2011. The combination of time-series InSAR analysis and old-dated DEM indicated revealed topographic changes associated the 2006 sliding event, which is confirmed by the difference of multiple LiDAR DEMs. Precipitation and discharge measurements before the 2006 and 2014 landslide events did not exhibit extremely anomalous records, suggesting the precipitation is not the controlling factor in determining the sliding events at Oso. The lack of surface deformation during 2006-2011 and weak correlation between the precipitation and the sliding event, suggest other factors (such as porosity) might play a critical role on the run-away events at this Oso and other similar landslides.

  10. Comparative transcriptome and proteome analysis to reveal the biosynthesis of gold nanoparticles in Arabidopsis.

    PubMed

    Tiwari, Manish; Krishnamurthy, Sneha; Shukla, Devesh; Kiiskila, Jeffrey; Jain, Ajay; Datta, Rupali; Sharma, Nilesh; Sahi, Shivendra V

    2016-02-23

    A large number of plants have been tested and exploited in search of a green chemistry approach for the fabrication of gold or other precious metal nanomaterials. Despite the potential of plant based methods, very little is known about the underlying biochemical reactions and genes involved in the biotransformation mechanism of AuCl4 into gold nanoparticles (AuNPs). In this research, we thus focused on studying the effect of Au on growth and nanoparticles formation by analyses of transcriptome, proteome and ionome shift in Arabidopsis. Au exposure favored the growth of Arabidopsis seedling and induced formation of nanoparticles in root and shoot, as indicated by optical and hyperspectral imaging. Root transcriptome analysis demonstrated the differential expression of the members of WRKY, MYB and BHLH gene families, which are involved in the Fe and other essential metals homeostasis. The proteome analysis revealed that Glutathione S-transferases were induced in the shoot and suggested its potential role in the biosynthesis AuNPs. This study also demonstrated the role of plant hormone auxin in determining the Au induced root system architecture. This is the first study using an integrated approach to understand the in planta biotransformation of KAuCl4 into AuNPs.

  11. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions

    PubMed Central

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I.; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B. H.

    2016-01-01

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions. PMID:27193869

  12. Integrative microbial community analysis reveals full-scale enhanced biological phosphorus removal under tropical conditions.

    PubMed

    Law, Yingyu; Kirkegaard, Rasmus Hansen; Cokro, Angel Anisa; Liu, Xianghui; Arumugam, Krithika; Xie, Chao; Stokholm-Bjerregaard, Mikkel; Drautz-Moses, Daniela I; Nielsen, Per Halkjær; Wuertz, Stefan; Williams, Rohan B H

    2016-05-19

    Management of phosphorus discharge from human waste is essential for the control of eutrophication in surface waters. Enhanced biological phosphorus removal (EBPR) is a sustainable, efficient way of removing phosphorus from waste water without employing chemical precipitation, but is assumed unachievable in tropical temperatures due to conditions that favour glycogen accumulating organisms (GAOs) over polyphosphate accumulating organisms (PAOs). Here, we show these assumptions are unfounded by studying comparative community dynamics in a full-scale plant following systematic perturbation of operational conditions, which modified community abundance, function and physicochemical state. A statistically significant increase in the relative abundance of the PAO Accumulibacter was associated with improved EBPR activity. GAO relative abundance also increased, challenging the assumption of competition. An Accumulibacter bin-genome was identified from a whole community metagenomic survey, and comparative analysis against extant Accumulibacter genomes suggests a close relationship to Type II. Analysis of the associated metatranscriptome data revealed that genes encoding proteins involved in the tricarboxylic acid cycle and glycolysis pathways were highly expressed, consistent with metabolic modelling results. Our findings show that tropical EBPR is indeed possible, highlight the translational potential of studying competition dynamics in full-scale waste water communities and carry implications for plant design in tropical regions.

  13. Comparative analysis of animal growth: a primate continuum revealed by a new dimensionless growth rate coefficient.

    PubMed

    Vinicius, Lucio; Mumby, Hannah S

    2013-05-01

    The comparative analysis of animal growth still awaits full integration into life-history studies, partially due to the difficulty of defining a comparable measure of growth rate across species. Using growth data from 50 primate species, we introduce a modified "general growth model" and a dimensionless growth rate coefficient β that controls for size scaling and phylogenetic effects in the distribution of growth rates. Our results contradict the prevailing idea that slow growth characterizes primates as a group: the observed range of β values shows that not all primates grow slowly, with galago species exhibiting growth rates similar or above the mammalian average, while other strepsirrhines and most New World monkeys show limited reduction in growth rates. Low growth rate characterizes apes and some papionines. Phylogenetic regressions reveal associations between β and life-history variables, providing tests for theories of primate growth evolution. We also show that primate slow growth is an exclusively postnatal phenomenon. Our study exemplifies how the dimensionless approach promotes the integration of growth rate data into comparative life-history analysis, and demonstrates its potential applicability to other cases of adaptive diversification of animal growth patterns.

  14. Independent component analysis of DTI data reveals white matter covariances in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Ouyang, Xin; Sun, Xiaoyu; Guo, Ting; Sun, Qiaoyue; Chen, Kewei; Yao, Li; Wu, Xia; Guo, Xiaojuan

    2014-03-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease with the clinical symptom of the continuous deterioration of cognitive and memory functions. Multiple diffusion tensor imaging (DTI) indices such as fractional anisotropy (FA) and mean diffusivity (MD) can successfully explain the white matter damages in AD patients. However, most studies focused on the univariate measures (voxel-based analysis) to examine the differences between AD patients and normal controls (NCs). In this investigation, we applied a multivariate independent component analysis (ICA) to investigate the white matter covariances based on FA measurement from DTI data in 35 AD patients and 45 NCs from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We found that six independent components (ICs) showed significant FA reductions in white matter covariances in AD compared with NC, including the genu and splenium of corpus callosum (IC-1 and IC-2), middle temporal gyral of temporal lobe (IC-3), sub-gyral of frontal lobe (IC-4 and IC-5) and sub-gyral of parietal lobe (IC-6). Our findings revealed covariant white matter loss in AD patients and suggest that the unsupervised data-driven ICA method is effective to explore the changes of FA in AD. This study assists us in understanding the mechanism of white matter covariant reductions in the development of AD.

  15. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell

    PubMed Central

    Skliros, Dimitrios; Kalatzis, Panos G.; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage–host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the “schizoT4like” clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD+ and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection. PMID:27895630

  16. Genomic and transcriptomic analysis of NDM-1 Klebsiella pneumoniae in spaceflight reveal mechanisms underlying environmental adaptability

    PubMed Central

    Li, Jia; Liu, Fei; Wang, Qi; Ge, Pupu; Woo, Patrick C. Y.; Yan, Jinghua; Zhao, Yanlin; Gao, George F.; Liu, Cui Hua; Liu, Changting

    2014-01-01

    The emergence and rapid spread of New Delhi Metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae strains has caused a great concern worldwide. To better understand the mechanisms underlying environmental adaptation of those highly drug-resistant K. pneumoniae strains, we took advantage of the China's Shenzhou 10 spacecraft mission to conduct comparative genomic and transcriptomic analysis of a NDM-1 K. pneumoniae strain (ATCC BAA-2146) being cultivated under different conditions. The samples were recovered from semisolid medium placed on the ground (D strain), in simulated space condition (M strain), or in Shenzhou 10 spacecraft (T strain) for analysis. Our data revealed multiple variations underlying pathogen adaptation into different environments in terms of changes in morphology, H2O2 tolerance and biofilm formation ability, genomic stability and regulation of metabolic pathways. Additionally, we found a few non-coding RNAs to be differentially regulated. The results are helpful for better understanding the adaptive mechanisms of drug-resistant bacterial pathogens. PMID:25163721

  17. Comparative transcriptome and proteome analysis to reveal the biosynthesis of gold nanoparticles in Arabidopsis

    PubMed Central

    Tiwari, Manish; Krishnamurthy, Sneha; Shukla, Devesh; Kiiskila, Jeffrey; Jain, Ajay; Datta, Rupali; Sharma, Nilesh; Sahi, Shivendra V.

    2016-01-01

    A large number of plants have been tested and exploited in search of a green chemistry approach for the fabrication of gold or other precious metal nanomaterials. Despite the potential of plant based methods, very little is known about the underlying biochemical reactions and genes involved in the biotransformation mechanism of AuCl4 into gold nanoparticles (AuNPs). In this research, we thus focused on studying the effect of Au on growth and nanoparticles formation by analyses of transcriptome, proteome and ionome shift in Arabidopsis. Au exposure favored the growth of Arabidopsis seedling and induced formation of nanoparticles in root and shoot, as indicated by optical and hyperspectral imaging. Root transcriptome analysis demonstrated the differential expression of the members of WRKY, MYB and BHLH gene families, which are involved in the Fe and other essential metals homeostasis. The proteome analysis revealed that Glutathione S-transferases were induced in the shoot and suggested its potential role in the biosynthesis AuNPs. This study also demonstrated the role of plant hormone auxin in determining the Au induced root system architecture. This is the first study using an integrated approach to understand the in planta biotransformation of KAuCl4 into AuNPs. PMID:26902325

  18. [Bacteria community in different aged Coptis chinensis planting soil revealed by PCR-DGGE analysis].

    PubMed

    Tan, Yuan; Chen, Qiang; Liu, Han-jun; Song, San-duo; Yu, Xiu-mei; Dong, Zhen-huan; Tang, Xue; Zhong, Yu-zhou

    2015-08-01

    In order to reveal the cause of disease occurred in the process of Coptis chinensis growth, this paper studied the bacterial species diversity index of different aged rhizospheric and non-rhizospheric soil planting normal or sick C. chinensis by using PCR-DGGE technique. The representative DGGE bands were chosen to be cloned, and sequenced, the phylogeny were constructed. The results showed that the bacterial communities were very different between the normal and diseased soil samples of C. chinensis, and the diversity index (H) of diseased soil samples were higher than that of normal soil samples. Sequencing analysis of representative cloned DGGE bands showed that the unculturable bacteria were the dominant groups, and bacteria belonged to genus Bacillus, Acidovorax, Acinetobacter, uncultured Kluyvera, and uncultured Comamonas were also existing, but the reported plant pathogenic bacteria were not found in the C. chinensis planting soil. The density and brightness of clone band d in diseased soil samples was higher than that in normal soil sample, and sequencing analysis showed that it belonged to genus Acidovorax. Obviously, during the process of C. chinensis growth, the rhizospheric bacteria population changed, and the quantity of bacteria belong Acidovorax increased, which probably resulted in the disease occurred during C. chinensis growth.

  19. Glycoproteomic Analysis of Seven Major Allergenic Proteins Reveals Novel Post-translational Modifications*

    PubMed Central

    Halim, Adnan; Carlsson, Michael C.; Madsen, Caroline Benedicte; Brand, Stephanie; Møller, Svenning Rune; Olsen, Carl Erik; Vakhrushev, Sergey Y.; Brimnes, Jens; Wurtzen, Peter Adler; Ipsen, Henrik; Petersen, Bent L.; Wandall, Hans H.

    2015-01-01

    Allergenic proteins such as grass pollen and house dust mite (HDM) proteins are known to trigger hypersensitivity reactions of the immune system, leading to what is commonly known as allergy. Key allergenic proteins including sequence variants have been identified but characterization of their post-translational modifications (PTMs) is still limited. Here, we present a detailed PTM1 characterization of a series of the main and clinically relevant allergens used in allergy tests and vaccines. We employ Orbitrap-based mass spectrometry with complementary fragmentation techniques (HCD/ETD) for site-specific PTM characterization by bottom-up analysis. In addition, top-down mass spectrometry is utilized for targeted analysis of individual proteins, revealing hitherto unknown PTMs of HDM allergens. We demonstrate the presence of lysine-linked polyhexose glycans and asparagine-linked N-acetylhexosamine glycans on HDM allergens. Moreover, we identified more complex glycan structures than previously reported on the major grass pollen group 1 and 5 allergens, implicating important roles for carbohydrates in allergen recognition and response by the immune system. The new findings are important for understanding basic disease-causing mechanisms at the cellular level, which ultimately may pave the way for instigating novel approaches for targeted desensitization strategies and improved allergy vaccines. PMID:25389185

  20. Phylogenetic analysis of vertebrate CXC chemokines reveals novel lineage specific groups in teleost fish.

    PubMed

    Chen, Jun; Xu, Qiaoqing; Wang, Tiehui; Collet, Bertrand; Corripio-Miyar, Yolanda; Bird, Steve; Xie, Ping; Nie, Pin; Secombes, Christopher J; Zou, Jun

    2013-10-01

    In this study, we have identified 421 molecules across the vertebrate spectrum and propose a unified nomenclature for CXC chemokines in fish, amphibians and reptiles based on phylogenetic analysis. Expanding on earlier studies in teleost fish, lineage specific CXC chemokines that have no apparent homologues in mammals were confirmed. Furthermore, in addition to the two subgroups of the CXCL8 homologues known in teleost fish, a third group was identified (termed CXCL8_L3), as was a further subgroup of the fish CXC genes related to CXCL11. Expression of the CXC chemokines found in rainbow trout, Oncorhynchus mykiss, was studied in response to stimulation with inflammatory and antiviral cytokines, and bacterial. Tissue distribution analysis revealed distinct expression profiles for these trout CXC chemokines. Lastly three of the trout chemokines, including two novel fish specific CXC chemokines containing three pairs of cysteines, were produced as recombinant proteins and their effect on trout leucocyte migration studied. These molecules increased the relative expression of CD4 and MCSFR in migrated cells in an in vitro chemotaxis assay.

  1. Bach Is the Father of Harmony: Revealed by a 1/f Fluctuation Analysis across Musical Genres.

    PubMed

    Wu, Dan; Kendrick, Keith M; Levitin, Daniel J; Li, Chaoyi; Yao, Dezhong

    2015-01-01

    Harmony is a fundamental attribute of music. Close connections exist between music and mathematics since both pursue harmony and unity. In music, the consonance of notes played simultaneously partly determines our perception of harmony; associates with aesthetic responses; and influences the emotion expression. The consonance could be considered as a window to understand and analyze harmony. Here for the first time we used a 1/f fluctuation analysis to investigate whether the consonance fluctuation structure in music with a wide range of composers and genres followed the scale free pattern that has been found for pitch, melody, rhythm, human body movements, brain activity, natural images and geographical features. We then used a network graph approach to investigate which composers were the most influential both within and across genres. Our results showed that patterns of consonance in music did follow scale-free characteristics, suggesting that this feature is a universally evolved one in both music and the living world. Furthermore, our network analysis revealed that Bach's harmony patterns were having the most influence on those used by other composers, followed closely by Mozart.

  2. mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe.

    PubMed Central

    Torroni, A; Bandelt, H J; D'Urbano, L; Lahermo, P; Moral, P; Sellitto, D; Rengo, C; Forster, P; Savontaus, M L; Bonné-Tamir, B; Scozzari, R

    1998-01-01

    mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data. PMID:9545392

  3. Structure analysis reveals the flexibility of the ADAMTS-5 active site

    SciTech Connect

    Shieh, Huey-Sheng; Tomasselli, Alfredo G.; Mathis, Karl J.; Schnute, Mark E.; Woodard, Scott S.; Caspers, Nicole; Williams, Jennifer M.; Kiefer, James R.; Munie, Grace; Wittwer, Arthur; Malfait, Anne-Marie; Tortorella, Micky D.

    2012-03-02

    A ((1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl) succinamide derivative (here referred to as Compound 12) shows significant activity toward many matrix metalloproteinases (MMPs), including MMP-2, MMP-8, MMP-9, and MMP-13. Modeling studies had predicted that this compound would not bind to ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin motifs-5) due to its shallow S1' pocket. However, inhibition analysis revealed it to be a nanomolar inhibitor of both ADAMTS-4 and -5. The observed inconsistency was explained by analysis of crystallographic structures, which showed that Compound 12 in complex with the catalytic domain of ADAMTS-5 (cataTS5) exhibits an unusual conformation in the S1' pocket of the protein. This first demonstration that cataTS5 can undergo an induced conformational change in its active site pocket by a molecule like Compound 12 should enable the design of new aggrecanase inhibitors with better potency and selectivity profiles.

  4. Intestinal transcriptome analysis revealed differential salinity adaptation between two tilapiine species.

    PubMed

    Ronkin, Dana; Seroussi, Eyal; Nitzan, Tali; Doron-Faigenboim, Adi; Cnaani, Avner

    2015-03-01

    Tilapias are a group of freshwater species, which vary in their ability to adapt to high salinity water. Osmotic regulation in fish is conducted mainly in the gills, kidney, and gastrointestinal tract (GIT). The mechanisms involved in ion and water transport through the GIT is not well-characterized, with only a few described complexes. Comparing the transcriptome of the anterior and posterior intestinal sections of a freshwater and saltwater adapted fish by deep-sequencing, we examined the salinity adaptation of two tilapia species: the high salinity-tolerant Oreochromis mossambicus (Mozambique tilapia), and the less salinity-tolerant Oreochromis niloticus (Nile tilapia). This comparative analysis revealed high similarity in gene expression response to salinity change between species in the posterior intestine and large differences in the anterior intestine. Furthermore, in the anterior intestine 68 genes were saltwater up-regulated in one species and down-regulated in the other species (47 genes up-regulated in O. niloticus and down-regulated in O. mossambicus, with 21 genes showing the reverse pattern). Gene ontology (GO) analysis showed a high proportion of transporter and ion channel function among these genes. The results of this study point to a group of genes that differed in their salinity-dependent regulation pattern in the anterior intestine as potentially having a role in the differential salinity tolerance of these two closely related species.

  5. Comparative Functional Genomic Analysis of Two Vibrio Phages Reveals Complex Metabolic Interactions with the Host Cell.

    PubMed

    Skliros, Dimitrios; Kalatzis, Panos G; Katharios, Pantelis; Flemetakis, Emmanouil

    2016-01-01

    Sequencing and annotation was performed for two large double stranded DNA bacteriophages, φGrn1 and φSt2 of the Myoviridae family, considered to be of great interest for phage therapy against Vibrios in aquaculture live feeds. In addition, phage-host metabolic interactions and exploitation was studied by transcript profiling of selected viral and host genes. Comparative genomic analysis with other large Vibrio phages was also performed to establish the presence and location of homing endonucleases highlighting distinct features for both phages. Phylogenetic analysis revealed that they belong to the "schizoT4like" clade. Although many reports of newly sequenced viruses have provided a large set of information, basic research related to the shift of the bacterial metabolism during infection remains stagnant. The function of many viral protein products in the process of infection is still unknown. Genome annotation identified the presence of several viral open reading frames (ORFs) participating in metabolism, including a Sir2/cobB (sirtuin) protein and a number of genes involved in auxiliary NAD(+) and nucleotide biosynthesis, necessary for phage DNA replication. Key genes were subsequently selected for detail study of their expression levels during infection. This work suggests a complex metabolic interaction and exploitation of the host metabolic pathways and biochemical processes, including a possible post-translational protein modification, by the virus during infection.

  6. Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

    PubMed

    Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

    2015-09-08

    Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

  7. Analysis of two 47,XXX males reveals X-Y interchange and maternal or paternal nondisjunction.

    PubMed

    Scherer, G; Schempp, W; Fraccaro, M; Bausch, E; Bigozzi, V; Maraschio, P; Montali, E; Simoni, G; Wolf, U

    1989-02-01

    Two cases of 47,XXX males were studied, one of which has been published previously (Bigozzi et al. 1980). Analysis of X-linked restriction fragment length polymorphisms revealed that in this case, one X chromosome was of paternal and two were of maternal origin, whereas in the other case, two X chromosomes were of paternal and one of maternal origin. Southern blot analysis with Y-specific DNA probes demonstrated the presence of Y short arm sequences in both XXX males. In one case, the results obtained pointed to a paracentric inversion on Yp of the patient's father. In situ hybridization indicated that the Y-specific DNA sequences were localized on Xp22.3 in one of the three X chromosomes in both cases. The presence of Y DNA had no effect on random X inactivation. It is concluded that both XXX males originate from aberrant X-Y interchange during paternal meiosis, with coincident nondisjunction of the X chromosome during maternal meiosis in case 1, and during paternal meiosis II in case 2.

  8. Applying risk adjusted cost-effectiveness (RAC-E) analysis to hospitals: estimating the costs and consequences of variation in clinical practice.

    PubMed

    Karnon, Jonathan; Caffrey, Orla; Pham, Clarabelle; Grieve, Richard; Ben-Tovim, David; Hakendorf, Paul; Crotty, Maria

    2013-06-01

    Cost-effectiveness analysis is well established for pharmaceuticals and medical technologies but not for evaluating variations in clinical practice. This paper describes a novel methodology--risk adjusted cost-effectiveness (RAC-E)--that facilitates the comparative evaluation of applied clinical practice processes. In this application, risk adjustment is undertaken with a multivariate matching algorithm that balances the baseline characteristics of patients attending different settings (e.g., hospitals). Linked, routinely collected data are used to analyse patient-level costs and outcomes over a 2-year period, as well as to extrapolate costs and survival over patient lifetimes. The study reports the relative cost-effectiveness of alternative forms of clinical practice, including a full representation of the statistical uncertainty around the mean estimates. The methodology is illustrated by a case study that evaluates the relative cost-effectiveness of services for patients presenting with acute chest pain across the four main public hospitals in South Australia. The evaluation finds that services provided at two hospitals were dominated, and of the remaining services, the more effective hospital gained life years at a low mean additional cost and had an 80% probability of being the most cost-effective hospital at realistic cost-effectiveness thresholds. Potential determinants of the estimated variation in costs and effects were identified, although more detailed analyses to identify specific areas of variation in clinical practice are required to inform improvements at the less cost-effective institutions.

  9. Transcriptome analysis reveals specific modulation of abscisic acid signaling by ROP10 small GTPase in Arabidopsis.

    PubMed

    Xin, Zeyu; Zhao, Yihong; Zheng, Zhi-Liang

    2005-11-01

    Abscisic acid (ABA) is a hormone that modulates a variety of agronomically important growth and developmental processes and various stresses responses, but its signal transduction pathways remain poorly understood. ROP10, a member of ROP small GTPases in Arabidopsis (Arabidopsis thaliana), is a plasma membrane-associated protein specifically involved in negative regulation of ABA responses. To dissect the ROP10-mediated ABA signaling, we carried out transcriptome analysis using the Arabidopsis full-genome chip. Our analysis revealed a total of 262 and 125 genes that were, respectively, up- and down-regulated (> or =2-fold cutoff) by 1 mum ABA in wild type (Wassilewskija [Ws]); 42 up-regulated and 38 down-regulated genes have not been identified in other studies. Consistent with the nonpleiotropic phenotypes of rop10-1, only three genes were altered in rop10-1 in the absence of ABA treatment. In response to 1 microm ABA, 341 and 127 genes were, respectively, activated and repressed in rop10-1. Interestingly, a particular subset of 21 genes that were not altered by 1 microm ABA in Ws but only activated in rop10-1 was identified. Reverse transcription-polymerase chain reaction analysis revealed the existence of three distinct categories of ABA dose-response patterns. One novel category is characterized by their ABA unresponsiveness in Ws and activation in rop10-1 at 1 microm but not 10 and 100 microm of ABA. This indicates that ROP10 gates the expression of genes that are specific to low concentrations of ABA. Furthermore, almost all of these 21 genes are known to be highly induced by various biotic and abiotic stresses. Consequently, we found that rop10-1 enhanced the sensitivity of seed germination inhibition to mannitol and sodium chloride. Our results suggest that ROP10 negatively regulates ABA responses by specifically and differentially modulating the ABA sensitivity of a subset of genes including protein kinases and zinc-finger family proteins.

  10. Family Adjustment of Single Parents in the U. S. Army: An Empirical Analysis of Work Stressors and Adaptive Resources

    DTIC Science & Technology

    1993-08-01

    0: cca m w 0 0n ~C4 CR *4~ c.0 t- 00r ’wa -. cgq Cog I .~ ~ 15 Regression Analysis* Single MotherS Table 8 presents the results from the hierarchical...Research Institute for the Behavioral and Social Sciences. (AD A225 085) Orthner, D.K., Bowen, G.L., & Beare, V.G. (1990). The organization family: A

  11. Co-expression network analysis reveals transcription factors associated to cell wall biosynthesis in sugarcane.

    PubMed

    Ferreira, Savio Siqueira; Hotta, Carlos Takeshi; Poelking, Viviane Guzzo de Carli; Leite, Debora Chaves Coelho; Buckeridge, Marcos Silveira; Loureiro, Marcelo Ehlers; Barbosa, Marcio Henrique Pereira; Carneiro, Monalisa Sampaio; Souza, Glaucia Mendes

    2016-05-01

    Sugarcane is a hybrid of Saccharum officinarum and Saccharum spontaneum, with minor contributions from other species in Saccharum and other genera. Understanding the molecular basis of cell wall metabolism in sugarcane may allow for rational changes in fiber quality and content when designing new energy crops. This work describes a comparative expression profiling of sugarcane ancestral genotypes: S. officinarum, S. spontaneum and S. robustum and a commercial hybrid: RB867515, linking gene expression to phenotypes to identify genes for sugarcane improvement. Oligoarray experiments of leaves, immature and intermediate internodes, detected 12,621 sense and 995 antisense transcripts. Amino acid metabolism was particularly evident among pathways showing natural antisense transcripts expression. For all tissues sampled, expression analysis revealed 831, 674 and 648 differentially expressed genes in S. officinarum, S. robustum and S. spontaneum, respectively, using RB867515 as reference. Expression of sugar transporters might explain sucrose differences among genotypes, but an unexpected differential expression of histones were also identified between high and low Brix° genotypes. Lignin biosynthetic genes and bioenergetics-related genes were up-regulated in the high lignin genotype, suggesting that these genes are important for S. spontaneum to allocate carbon to lignin, while S. officinarum allocates it to sucrose storage. Co-expression network analysis identified 18 transcription factors possibly related to cell wall biosynthesis while in silico analysis detected cis-elements involved in cell wall biosynthesis in their promoters. Our results provide information to elucidate regulatory networks underlying traits of interest that will allow the improvement of sugarcane for biofuel and chemicals production.

  12. ALE meta‐analysis reveals dissociable networks for affective and discriminative aspects of touch

    PubMed Central

    2016-01-01

    Abstract Emotionally‐laden tactile stimulation—such as a caress on the skin or the feel of velvet—may represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta‐analysis was performed. This meta‐analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n = 291, 34 experimental contrasts). A separate ALE meta‐analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n = 1,075, 91 experimental contrasts). These meta‐analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta‐analytic connectivity (MCAM) analyses investigated network‐level co‐activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective‐related PI and discriminative‐related SI regions co‐activated with different networks, implicated in dissociable functions, but sharing somatosensory co‐activations. Taken together, these meta‐analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct

  13. Time series analysis of satellite data reveals continuous deforestation of New England since the 1980s

    NASA Astrophysics Data System (ADS)

    Olofsson, Pontus; Holden, Christopher E.; Bullock, Eric L.; Woodcock, Curtis E.

    2016-06-01

    Land cover and land change were monitored continuously between 1985 and 2011 at 30 m resolution across New England in the Northeastern United States in support of modeling the terrestrial carbon budget. It was found that the forest area has been decreasing throughout the study period in each state of the region since the 1980s. A total of 386 657 ± 98 137 ha (95% confidence interval) of forest has been converted to other land covers since 1985. Mainly driven by low density residential development, the deforestation accelerated in the mid-1990s until 2007 when it plateaued as a result of declining new residential construction and in turn, the financial crisis of 2007-08. The area of forest harvest, estimated at 226 519 ± 66 682 ha, was mapped separately and excluded from the deforestation estimate, while the area of forest expansion on non-forested lands was found to not be significantly different from zero. New England is often held as a principal example of a forest transition with historical widespread deforestation followed by recovery of forestlands as farming activities diminished, but the results of this study support the notion of a reversal of the forest transition as the region again is experiencing widespread deforestation. All available Landsat imagery acquired after 1985 for the study area were collected and used in the analysis. Areas of land cover and land change were estimated from a random sample of reference observations stratified by a twelve-class land change map encompassing the entire study area and period. The statistical analysis revealed that the net change in forest area and the associated modeled impact on the terrestrial carbon balance would have been considerably different if the results of the map were used without inferring the area of forest change by analysis of a reference sample.

  14. Global RNA Half-Life Analysis in Escherichia coli Reveals Positional Patterns of Transcript Degradation

    PubMed Central

    Selinger, Douglas W.; Saxena, Rini Mukherjee; Cheung, Kevin J.; Church, George M.; Rosenow, Carsten

    2003-01-01

    Subgenic-resolution oligonucleotide microarrays were used to study global RNA degradation in wild-type Escherichia coli MG1655. RNA chemical half-lives were measured for 1036 open reading frames (ORFs) and for 329 known and predicted operons. The half-life of total mRNA was 6.8 min under the conditions tested. We also observed significant relationships between gene functional assignments and transcript stability. Unexpectedly, transcription of a single operon (tdcABCDEFG) was relatively rifampicin-insensitive and showed significant increases 2.5 min after rifampicin addition. This supports a novel mechanism of transcription for the tdc operon, whose promoter lacks any recognizable ς binding sites. Probe by probe analysis of all known and predicted operons showed that the 5′ ends of operons degrade, on average, more quickly than the rest of the transcript, with stability increasing in a 3′ direction, supporting and further generalizing the current model of a net 5′ to 3′ directionality of degradation. Hierarchical clustering analysis of operon degradation patterns revealed that this pattern predominates but is not exclusive. We found a weak but highly significant correlation between the degradation of adjacent operon regions, suggesting that stability is determined by a combination of local and operon-wide stability determinants. The 16 ORF dcw gene cluster, which has a complex promoter structure and a partially characterized degradation pattern, was studied at high resolution, allowing a detailed and integrated description of its abundance and degradation. We discuss the application of subgenic resolution DNA microarray analysis to study global mechanisms of RNA transcription and processing. PMID:12566399

  15. ALE meta-analysis reveals dissociable networks for affective and discriminative aspects of touch.

    PubMed

    Morrison, India

    2016-04-01

    Emotionally-laden tactile stimulation-such as a caress on the skin or the feel of velvet-may represent a functionally distinct domain of touch, underpinned by specific cortical pathways. In order to determine whether, and to what extent, cortical functional neuroanatomy supports a distinction between affective and discriminative touch, an activation likelihood estimate (ALE) meta-analysis was performed. This meta-analysis statistically mapped reported functional magnetic resonance imaging (fMRI) activations from 17 published affective touch studies in which tactile stimulation was associated with positive subjective evaluation (n = 291, 34 experimental contrasts). A separate ALE meta-analysis mapped regions most likely to be activated by tactile stimulation during detection and discrimination tasks (n = 1,075, 91 experimental contrasts). These meta-analyses revealed dissociable regions for affective and discriminative touch, with posterior insula (PI) more likely to be activated for affective touch, and primary somatosensory cortices (SI) more likely to be activated for discriminative touch. Secondary somatosensory cortex had a high likelihood of engagement by both affective and discriminative touch. Further, meta-analytic connectivity (MCAM) analyses investigated network-level co-activation likelihoods independent of task or stimulus, across a range of domains and paradigms. Affective-related PI and discriminative-related SI regions co-activated with different networks, implicated in dissociable functions, but sharing somatosensory co-activations. Taken together, these meta-analytic findings suggest that affective and discriminative touch are dissociable both on the regional and network levels. However, their degree of shared activation likelihood in somatosensory cortices indicates that this dissociation reflects functional biases within tactile processing networks, rather than functionally and anatomically distinct pathways.

  16. Bulk Segregant Analysis Reveals the Genetic Basis of a Natural Trait Variation in Fission Yeast

    PubMed Central

    Hu, Wen; Suo, Fang; Du, Li-Lin

    2015-01-01

    Although the fission yeast Schizosaccharomyces pombe is a well-established model organism, studies of natural trait variations in this species remain limited. To assess the feasibility of segregant-pool-based mapping of phenotype-causing genes in natural strains of fission yeast, we investigated the cause of a maltose utilization defect (Mal-) of the S. pombe strain CBS5557 (originally known as Schizosaccharomyces malidevorans). Analyzing the genome sequence of CBS5557 revealed 955 nonconservative missense substitutions, and 61 potential loss-of-function variants including 47 frameshift indels, 13 early stop codons, and 1 splice site mutation. As a side benefit, our analysis confirmed 146 sequence errors in the reference genome and improved annotations of 27 genes. We applied bulk segregant analysis to map the causal locus of the Mal- phenotype. Through sequencing the segregant pools derived from a cross between CBS5557 and the laboratory strain, we located the locus to within a 2.23-Mb chromosome I inversion found in most S. pombe isolates including CBS5557. To map genes within the inversion region that occupies 18% of the genome, we created a laboratory strain containing the same inversion. Analyzing segregants from a cross between CBS5557 and the inversion-containing laboratory strain narrowed down the locus to a 200-kb interval and led us to identify agl1, which suffers a 5-bp deletion in CBS5557, as the causal gene. Interestingly, loss of agl1 through a 34-kb deletion underlies the Mal- phenotype of another S. pombe strain CGMCC2.1628. This work adapts and validates the bulk segregant analysis method for uncovering trait-gene relationship in natural fission yeast strains. PMID:26615217

  17. Analysis of the interplay between methylation and expression reveals its potential role in cancer aetiology.

    PubMed

    Ozer, Bugra; Sezerman, Ugur

    2017-01-01

    With ongoing developments in technology, changes in DNA methylation levels have become prevalent to study cancer biology. Previous studies report that DNA methylation affects gene expression in a direct manner, most probably by blocking gene regulatory regions. In this study, we have studied the interplay between methylation and expression to improve our knowledge of cancer aetiology. For this purpose, we have investigated which genomic regions are of higher importance; hence, first exon, 5'UTR and 200 bp near the transcription start sites are proposed as being more crucial compared to other genomic regions. Furthermore, we have searched for a valid methylation level change threshold, and as a result, 25 % methylation change in previously determined genomic regions showed the highest inverse correlation with expression data. As a final step, we have examined the commonly affected genes and pathways by integrating methylation and expression information. Remarkably, the GPR115 gene and ErbB signalling pathway were found to be significantly altered for all cancer types in our analysis. Overall, combining methylation and expression information and identifying commonly affected genes and pathways in a variety of cancer types revealed new insights of cancer disease mechanisms. Moreover, compared to previous methylation-based studies, we have identified more important genomic regions and have defined a methylation change threshold level in order to obtain more reliable results. In addition to the novel analysis framework that involves the analysis of four different cancer types, our study exposes essential information regarding the contribution of methylation changes and its impact on cancer disease biology, which may facilitate the identification of new drug targets.

  18. Desiccation tolerance mechanism in resurrection fern-ally Selaginella tamariscina revealed by physiological and proteomic analysis.

    PubMed

    Wang, Xiaonan; Chen, Sixue; Zhang, Heng; Shi, Lei; Cao, Fenglin; Guo, Lihai; Xie, Yongming; Wang, Tai; Yan, Xiufeng; Dai, Shaojun

    2010-12-03

    Drought is one of the most severe limitations to plant growth and productivity. Resurrection plants have evolved a unique capability to tolerate desiccation in vegetative tissues. Fern-ally Selaginella tamariscina (Beauv.) is one of the most primitive vascular resurrection plants, which can survive a desiccated state and recover when water becomes available. To better understand the mechanism of desiccation tolerance, we have applied physiological and proteomic analysis. Samples of S. tamariscina were water-deprived for up to seven days followed by 12 h of rewatering. Our results showed that endogenous abscisic acid (ABA) increased to regulate dehydration-responsive genes/proteins and physiological processes. In the course of dehydration, the contents of osmolytes represented by soluble sugars and proline were increased to maintain cell structure integrity. The activities of four antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR)) also increased. In contrast, both the rate of photosynthesis and the chlorophyll content decreased, and plasma membrane integrity was lost. We identified 138 desiccation-responsive two-dimensional electrophoresis (2-DE) spots, representing 103 unique proteins. Hierarchical clustering analysis revealed that 83% of the proteins were down-regulated upon dehydration. They were mainly involved in photosynthesis, carbohydrate and energy metabolism, stress and defense, protein metabolism, signaling, membrane/transport, cell structure, and cell division. The dynamic expression changes of the desiccation-responsive proteins provide strong evidence that cell structure modification, photosynthesis reduction, antioxidant system activation, and protein post-transcriptional/translational modifications are essential to the poikilochlorophyllous fern-ally S. tamariscina in response to dehydration. In addition, our comparative analysis of dehydration-responsive proteins in vegetative tissues

  19. Nonlinear Hydrostatic Adjustment.

    NASA Astrophysics Data System (ADS)

    Bannon, Peter R.

    1996-12-01

    The final equilibrium state of Lamb's hydrostatic adjustment problem is found for finite amplitude heating. Lamb's problem consists of the response of a compressible atmosphere to an instantaneous, horizontally homogeneous heating. Results are presented for both isothermal and nonisothermal atmospheres.As in the linear problem, the fluid displacements are confined to the heated layer and to the region aloft with no displacement of the fluid below the heating. The region above the heating is displaced uniformly upward for heating and downward for cooling. The amplitudes of the displacements are larger for cooling than for warming.Examination of the energetics reveals that the fraction of the heat deposited into the acoustic modes increases linearly with the amplitude of the heating. This fraction is typically small (e.g., 0.06% for a uniform warming of 1 K) and is essentially independent of the lapse rate of the base-state atmosphere. In contrast a fixed fraction of the available energy generated by the heating goes into the acoustic modes. This fraction (e.g., 12% for a standard tropospheric lapse rate) agrees with the linear result and increases with increasing stability of the base-state atmosphere.The compressible results are compared to solutions using various forms of the soundproof equations. None of the soundproof equations predict the finite amplitude solutions accurately. However, in the small amplitude limit, only the equations for deep convection advanced by Dutton and Fichtl predict the thermodynamic state variables accurately for a nonisothermal base-state atmosphere.

  20. Nonlinear cardio-respiratory interactions revealed by time-phase bispectral analysis

    NASA Astrophysics Data System (ADS)

    Jamsek, Janez; Stefanovska, Aneta; McClintock, Peter V. E.

    2004-09-01

    Bispectral analysis based on high order statistics, introduced recently as a technique for revealing time-phase relationships among interacting noisy oscillators, has been used to study the nature of the coupling between cardiac and respiratory activity. Univariate blood flow signals recorded simultaneously by laser-Doppler flowmetry on both legs and arms were analysed. Coupling between cardiac and respiratory activity was also checked by use of bivariate data and computation of the cross-bispectrum between the ECG and respiratory signals. Measurements were made on six healthy males aged 25-27 years. Recordings were taken during spontaneous breathing (20 min), and during paced respiration at frequencies both lower and higher than that of spontaneous respiration (either two or three recordings with a constant frequency in the interval between 0.09 and 0.35 Hz). At each paced frequency recordings were taken for 12 min. It was confirmed that the dynamics of blood flow can usefully be considered in terms of coupled oscillators, and demonstrated that interactions between the cardiac and respiratory processes are weak and time-varying, and that they can be nonlinear. Nonlinear coupling was revealed to exist during both spontaneous and paced respiration. When present, it was detected in all four blood flow signals and in the cross-bispectrum between the ECG and respiratory signal. The episodes with nonlinear coupling were detected in 11 out of 22 recordings and lasted between 19 s in the case of high frequency (0.34 Hz) and 106 s in the case of low frequency paced respiration (0.11 Hz).

  1. Analysis of virus genomes from glacial environments reveals novel virus groups with unusual host interactions.

    PubMed

    Bellas, Christopher M; Anesio, Alexandre M; Barker, Gary

    2015-01-01

    Microbial communities in glacial ecosystems are diverse, active, and subjected to strong viral pressures and infection rates. In this study we analyse putative virus genomes assembled from three dsDNA viromes from cryoconite hole ecosystems of Svalbard and the Greenland Ice Sheet to assess the potential hosts and functional role viruses play in these habitats. We assembled 208 million reads from the virus-size fraction and developed a procedure to select genuine virus scaffolds from cellular contamination. Our curated virus library contained 546 scaffolds up to 230 Kb in length, 54 of which were circular virus consensus genomes. Analysis of virus marker genes revealed a wide range of viruses had been assembled, including bacteriophages, cyanophages, nucleocytoplasmic large DNA viruses and a virophage, with putative hosts identified as Cyanobacteria, Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes, eukaryotic algae and amoebae. Whole genome comparisons revealed the majority of circular genome scaffolds (CGS) formed 12 novel groups, two of which contained multiple phage members with plasmid-like properties, including a group of phage-plasmids possessing plasmid-like partition genes and toxin-antitoxin addiction modules to ensure their replication and a satellite phage-plasmid group. Surprisingly we also assembled a phage that not only encoded plasmid partition genes, but a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas adaptive bacterial immune system. One of the spacers was an exact match for another phage in our virome, indicating that in a novel use of the system, the lysogen was potentially capable of conferring immunity on its bacterial host against other phage. Together these results suggest that highly novel and diverse groups of viruses are present in glacial environments, some of which utilize very unusual life strategies and genes to control their replication and maintain a long-term relationship with their hosts.

  2. Dysconnection Topography in Schizophrenia Revealed with State-Space Analysis of EEG

    PubMed Central

    Jalili, Mahdi; Lavoie, Suzie; Deppen, Patricia; Meuli, Reto; Do, Kim Q.; Cuénod, Michel; Hasler, Martin

    2007-01-01

    Background The dysconnection hypothesis has been proposed to account for pathophysiological mechanisms underlying schizophrenia. Widespread structural changes suggesting abnormal connectivity in schizophrenia have been imaged. A functional counterpart of the structural maps would be the EEG synchronization maps. However, due to the limits of currently used bivariate methods, functional correlates of dysconnection are limited to the isolated measurements of synchronization between preselected pairs of EEG signals. Methods/Results To reveal a whole-head synchronization topography in schizophrenia, we applied a new method of multivariate synchronization analysis called S-estimator to the resting dense-array (128 channels) EEG obtained from 14 patients and 14 controls. This method determines synchronization from the embedding dimension in a state-space domain based on the theoretical consequence of the cooperative behavior of simultaneous time series—the shrinking of the state-space embedding dimension. The S-estimator imaging revealed a specific synchronization landscape in schizophrenia patients. Its main features included bilaterally increased synchronization over temporal brain regions and decreased synchronization over the postcentral/parietal region neighboring the midline. The synchronization topography was stable over the course of several months and correlated with the severity of schizophrenia symptoms. In particular, direct correlations linked positive, negative, and general psychopathological symptoms to the hyper-synchronized temporal clusters over both hemispheres. Along with these correlations, general psychopathological symptoms inversely correlated within the hypo-synchronized postcentral midline region. While being similar to the structural maps of cortical changes in schizophrenia, the S-maps go beyond the topography limits, demonstrating a novel aspect of the abnormalities of functional cooperation: namely, regionally reduced or enhanced

  3. Analysis of virus genomes from glacial environments reveals novel virus groups with unusual host interactions

    PubMed Central

    Bellas, Christopher M.; Anesio, Alexandre M.; Barker, Gary

    2015-01-01

    Microbial communities in glacial ecosystems are diverse, active, and subjected to strong viral pressures and infection rates. In this study we analyse putative virus genomes assembled from three dsDNA viromes from cryoconite hole ecosystems of Svalbard and the Greenland Ice Sheet to assess the potential hosts and functional role viruses play in these habitats. We assembled 208 million reads from the virus-size fraction and developed a procedure to select genuine virus scaffolds from cellular contamination. Our curated virus library contained 546 scaffolds up to 230 Kb in length, 54 of which were circular virus consensus genomes. Analysis of virus marker genes revealed a wide range of viruses had been assembled, including bacteriophages, cyanophages, nucleocytoplasmic large DNA viruses and a virophage, with putative hosts identified as Cyanobacteria, Alphaproteobacteria, Gammaproteobacteria, Actinobacteria, Firmicutes, eukaryotic algae and amoebae. Whole genome comparisons revealed the majority of circular genome scaffolds (CGS) formed 12 novel groups, two of which contained multiple phage members with plasmid-like properties, including a group of phage-plasmids possessing plasmid-like partition genes and toxin-antitoxin addiction modules to ensure their replication and a satellite phage-plasmid group. Surprisingly we also assembled a phage that not only encoded plasmid partition genes, but a clustered regularly interspaced short palindromic repeat (CRISPR)/Cas adaptive bacterial immune system. One of the spacers was an exact match for another phage in our virome, indicating that in a novel use of the system, the lysogen was potentially capable of conferring immunity on its bacterial host against other phage. Together these results suggest that highly novel and diverse groups of viruses are present in glacial environments, some of which utilize very unusual life strategies and genes to control their replication and maintain a long-term relationship with their hosts

  4. Structural and functional analysis of amphioxus HIFα reveals ancient features of the HIFα family.

    PubMed

    Gao, Shan; Lu, Ling; Bai, Yan; Zhang, Peng; Song, Weibo; Duan, Cunming

    2014-04-01

    Hypoxia-inducible factors (HIFs) are master regulators of the transcriptional response to hypoxia. To gain insight into the structural and functional evolution of the HIF family, we characterized the HIFα gene from amphioxus, an invertebrate chordate, and identified several alternatively spliced HIFα isoforms. Whereas HIFα Ia, the full-length isoform, contained a complete oxygen-dependent degradation (ODD) domain, the isoforms Ib, Ic, and Id had 1 or 2 deletions in the ODD domain. When tagged with GFP and tested in mammalian cells, the amphioxus HIFα Ia protein level increased in response to hypoxia or CoCl2 treatment, whereas HIFα Ib, Ic, and Id showed reduced or no hypoxia regulation. Deletion of the ODD sequence in HIFα Ia up-regulated the HIFα Ia levels under normoxia. Gene expression analysis revealed HIFα Ic to be the predominant isoform in embryos and larvae, whereas isoform Ia was the most abundant form in the adult stage. The expression levels of Ib and Id were very low. Hypoxia treatment of adults had no effect on the mRNA levels of these HIFα isoforms. Functional analyses in mammalian cells showed all 4 HIFα isoforms capable of entering the nucleus and activating hypoxia response element-dependent reporter gene expression. The functional nuclear location signal (NLS) mapped to 3 clusters of basic residues. (775)KKARL functioned as the primary NLS, but (737)KRK and (754)KK also contributed to the nuclear localization. All amphioxus HIFα isoforms had 2 functional transactivation domains (TADs). Its C-terminal transactivation (C-TAD) shared high sequence identity with the human HIF-1α and HIF-2α C-TAD. This domain contained a conserved asparagine, and its mutation resulted in an increase in transcriptional activity. These findings reveal many ancient features of the HIFα family and provide novel insights into the evolution of the HIFα family.

  5. Analysis of SSH library of rice variety Aganni reveals candidate gall midge resistance genes.

    PubMed

    Divya, Dhanasekar; Singh, Y Tunginba; Nair, Suresh; Bentur, J S

    2016-03-01

    The Asian rice gall midge, Orseolia oryzae, is a serious insect pest causing extensive yield loss. Interaction between the gall midge and rice genotypes is known to be on a gene-for-gene basis. Here, we report molecular basis of HR- (hypersensitive reaction-negative) type of resistance in Aganni (an indica rice variety possessing gall midge resistance gene Gm8) through the construction and analysis of a suppressive subtraction hybridization (SSH) cDNA library. In all, 2,800 positive clones were sequenced and analyzed. The high-quality ESTs were assembled into 448 non-redundant gene sequences. Homology search with the NCBI databases, using BlastX and BlastN, revealed that 73% of the clones showed homology to genes with known function and majority of ESTs belonged to the gene ontology category 'biological process'. Validation of 27 putative candidate gall midge resistance genes through real-time PCR, following gall midge infestation, in contrasting parents and their derived pre-NILs (near isogenic lines) revealed induction of specific genes related to defense and metabolism. Interestingly, four genes, belonging to families of leucine-rich repeat (LRR), heat shock protein (HSP), pathogenesis related protein (PR), and NAC domain-containing protein, implicated in conferring HR+ type of resistance, were found to be up-regulated in Aganni. Two of the reactive oxygen intermediates (ROI)-scavenging-enzyme-coding genes Cytosolic Ascorbate Peroxidase1, 2 (OsAPx1 and OsAPx2) were found up-regulated in Aganni in incompatible interaction possibly suppressing HR. We suggest that Aganni has a deviant form of inducible, salicylic acid (SA)-mediated resistance but without HR.

  6. Acetylproteomic analysis reveals functional implications of lysine acetylation in human spermatozoa (sperm).

    PubMed

    Yu, Heguo; Diao, Hua; Wang, Chunmei; Lin, Yan; Yu, Fudong; Lu, Hui; Xu, Wei; Li, Zheng; Shi, Huijuan; Zhao, Shimin; Zhou, Yuchuan; Zhang, Yonglian

    2015-04-01

    Male infertility is a medical condition that has been on the rise globally. Lysine acetylation of human sperm, an essential posttranslational modification involved in the etiology of sperm abnormality, is not fully understood. Therefore, we first generated a qualified pan-anti-acetyllysine monoclonal antibody to characterize the global lysine acetylation of uncapacitated normal human sperm with a proteomics approach. With high enrichment ratios that were up to 31%, 973 lysine-acetylated sites that matched to 456 human sperm proteins, including 671 novel lysine acetylation sites and 205 novel lysine-acetylated proteins, were identified. These proteins exhibited conserved motifs XXXKYXXX, XXXKFXXX, and XXXKHXXX, were annotated to function in multiple metabolic processes, and were localized predominantly in the mitochondrion and cytoplasmic fractions. Between the uncapacitated and capacitated sperm, different acetylation profiles in regard to functional proteins involved in sperm capacitation, sperm-egg recognition, sperm-egg plasma fusion, and fertilization were observed, indicating that acetylation of functional proteins may be required during sperm capacitation. Bioinformatics analysis revealed association of acetylated proteins with diseases and drugs. Novel acetylation of voltage-dependent anion channel proteins was also found. With clinical sperm samples, we observed differed lysine acetyltransferases and lysine deacetylases expression between normal sperm and abnormal sperm of asthenospermia or necrospermia. Furthermore, with sperm samples impaired by epigallocatechin gallate to mimic asthenospermia, we observed that inhibition of sperm motility was partly through the blockade of voltage-dependent anion channel 2 Lys-74 acetylation combined with reduced ATP levels and mitochondrial membrane potential. Taken together, we obtained a qualified pan-anti-acetyllysine monoclonal antibody, analyzed the acetylproteome of uncapacitated human sperm, and revealed

  7. Genome sequencing and analysis reveals possible determinants of Staphylococcus aureus nasal carriage

    PubMed Central

    Sivaraman, Karthikeyan; Venkataraman, Nitya; Tsai, Jennifer; Dewell, Scott; Cole, Alexander M

    2008-01-01

    Background Nasal carriage of Staphylococcus aureus is a major risk factor in clinical and community settings due to the range of etiologies caused by the organism. We have identified unique immunological and ultrastructural properties associated with nasal carriage isolates denoting a role for bacterial factors in nasal carriage. However, despite extensive molecular level characterizations by several groups suggesting factors necessary for colonization on nasal epithelium, genetic determinants of nasal carriage are unknown. Herein, we have set a genomic foundation for unraveling the bacterial determinants of nasal carriage in S. aureus. Results MLST analysis revealed no lineage specific differences between carrier and non-carrier strains suggesting a role for mobile genetic elements. We completely sequenced a model carrier isolate (D30) and a model non-carrier strain (930918-3) to identify differential gene content. Comparison revealed the presence of 84 genes unique to the carrier strain and strongly suggests a role for Type VII secretion systems in nasal carriage. These genes, along with a putative pathogenicity island (SaPIBov) present uniquely in the carrier strains are likely important in affecting carriage. Further, PCR-based genotyping of other clinical isolates for a specific subset of these 84 genes raise the possibility of nasal carriage being caused by multiple gene sets. Conclusion Our data suggest that carriage is likely a heterogeneic phenotypic trait and implies a role for nucleotide level polymorphism in carriage. Complete genome level analyses of multiple carriage strains of S. aureus will be important in clarifying molecular determinants of S. aureus nasal carriage. PMID:18808706

  8. Analysis of Nearly One Thousand Mammalian Mirtrons Reveals Novel Features of Dicer Substrates

    PubMed Central

    Shenker, Sol; Mohammed, Jaaved; Lai, Eric C.

    2015-01-01

    Mirtrons are microRNA (miRNA) substrates that utilize the splicing machinery to bypass the necessity of Drosha cleavage for their biogenesis. Expanding our recent efforts for mammalian mirtron annotation, we use meta-analysis of aggregate datasets to identify ~500 novel mouse and human introns that confidently generate diced small RNA duplexes. These comprise nearly 1000 total loci distributed in four splicing-mediated biogenesis subclasses, with 5'-tailed mirtrons as, by far, the dominant subtype. Thus, mirtrons surprisingly comprise a substantial fraction of endogenous Dicer substrates in mammalian genomes. Although mirtron-derived small RNAs exhibit overall expression correlation with their host mRNAs, we observe a subset with substantial differences that suggest regulated processing or accumulation. We identify characteristic sequence, length, and structural features of mirtron loci that distinguish them from bulk introns, and find that mirtrons preferentially emerge from genes with larger numbers of introns. While mirtrons generate miRNA-class regulatory RNAs, we also find that mirtrons exhibit many features that distinguish them from canonical miRNAs. We observe that conventional mirtron hairpins are substantially longer than Drosha-generated pre-miRNAs, indicating that the characteristic length of canonical pre-miRNAs is not a general feature of Dicer substrate hairpins. In addition, mammalian mirtrons exhibit unique patterns of ordered 5' and 3' heterogeneity, which reveal hidden complexity in miRNA processing pathways. These include broad 3'-uridylation of mirtron hairpins, atypically heterogeneous 5' termini that may result from exonucleolytic processing, and occasionally robust decapitation of the 5' guanine (G) of mirtron-5p species defined by splicing. Altogether, this study reveals that this extensive class of non-canonical miRNA bears a multitude of characteristic properties, many of which raise general mechanistic questions regarding the processing

  9. Systematic prioritization and integrative analysis of copy number variations in schizophrenia reveal key schizophrenia susceptibility genes.

    PubMed

    Luo, Xiongjian; Huang, Liang; Han, Leng; Luo, Zhenwu; Hu, Fang; Tieu, Roger; Gan, Lin

    2014-11-01

    Schizophrenia is a common mental disorder with high heritability and strong genetic heterogeneity. Common disease-common variants hypothesis predicts that schizophrenia is attributable in part to common genetic variants. However, recent studies have clearly demonstrated that copy number variations (CNVs) also play pivotal roles in schizophrenia susceptibility and explain a proportion of missing heritability. Though numerous CNVs have been identified, many of the regions affected by CNVs show poor overlapping among different studies, and it is not known whether the genes disrupted by CNVs contribute to the risk of schizophrenia. By using cumulative scoring, we systematically prioritized the genes affected by CNVs in schizophrenia. We identified 8 top genes that are frequently disrupted by CNVs, including NRXN1, CHRNA7, BCL9, CYFIP1, GJA8, NDE1, SNAP29, and GJA5. Integration of genes affected by CNVs with known schizophrenia susceptibility genes (from previous genetic linkage and association studies) reveals that many genes disrupted by CNVs are also associated with schizophrenia. Further protein-protein interaction (PPI) analysis indicates that protein products of genes affected by CNVs frequently interact with known schizophrenia-associated proteins. Finally, systematic integration of CNVs prioritization data with genetic association and PPI data identifies key schizophrenia candidate genes. Our results provide a global overview of genes impacted by CNVs in schizophrenia and reveal a densely interconnected molecular network of de novo CNVs in schizophrenia. Though the prioritized top genes represent promising schizophrenia risk genes, further work with different prioritization methods and independent samples is needed to confirm these findings. Nevertheless, the identified key candidate genes may have important roles in the pathogenesis of schizophrenia, and further functional characterization of these genes may provide pivotal targets for future therapeutics and

  10. Large-Scale Meta-Analysis of Human Medial Frontal Cortex Reveals Tripartite Functional Organization

    PubMed Central

    Chang, Luke J.; Banich, Marie T.; Wager, Tor D.; Yarkoni, Tal

    2016-01-01

    The functional organization of human medial frontal cortex (MFC) is a subject of intense study. Using fMRI, the MFC has been associated with diverse psychological processes, including motor function, cognitive control, affect, and social cognition. However, there have been few large-scale efforts to comprehensively map specific psychological functions to subregions of medial frontal anatomy. Here we applied a meta-analytic data-driven approach to nearly 10,000 fMRI studies to identify putatively separable regions of MFC and determine which psychological states preferentially recruit their activation. We identified regions at several spatial scales on the basis of meta-analytic coactivation, revealing three broad functional zones along a rostrocaudal axis composed of 2–4 smaller subregions each. Multivariate classification analyses aimed at identifying the psychological functions most strongly predictive of activity in each region revealed a tripartite division within MFC, with each zone displaying a relatively distinct functional signature. The posterior zone was associated preferentially with motor function, the middle zone with cognitive control, pain, and affect, and the anterior with reward, social processing, and episodic memory. Within each zone, the more fine-grained subregions showed distinct, but subtler, variations in psychological function. These results provide hypotheses about the functional organization of medial prefrontal cortex that can be tested explicitly in future studies. SIGNIFICANCE STATEMENT Activation of medial frontal cortex in fMRI studies is associated with a wide range of psychological states ranging from cognitive control to pain. However, this high rate of activation makes it challenging to determine how these various processes are topologically organized across medial frontal anatomy. We conducted a meta-analysis across nearly 10,000 studies to comprehensively map psychological states to discrete subregions in medial frontal cortex

  11. Transcriptomic analysis reveals importance of ROS and phytohormones in response to short-term salinity stress in Populus tomentosa

    PubMed Central

    Zheng, Lingyu; Meng, Yu; Ma, Jing; Zhao, Xiulian; Cheng, Tielong; Ji, Jing; Chang, Ermei; Meng, Chen; Deng, Nan; Chen, Lanzhen; Shi, Shengqing; Jiang, Zeping

    2015-01-01

    Populus tomentosa (Chinese white poplar) is well adapted to various extreme environments, and is considered an important species to study the effects of salinity stress on poplar trees. To decipher the mechanism of poplar's rapid response to short-term salinity stress, we firstly detected the changes in H2O2 and hormone, and then profiled the gene expression pattern of 10-week-old seedling roots treated with 200 mM NaCl for 0, 6, 12, and 24 h (h) by RNA-seq on the Illumina-Solexa platform. Physiological determination showed that the significant increase in H2O2 began at 6 h, while that in hormone ABA was at 24 h, under salt stress. Compared with controls (0 h), 3991, 4603, and 4903 genes were up regulated, and 1408, 2206, and 3461 genes were down regulated (adjusted P ≤ 0.05 and |log2Ratio|≥1) at 6, 12, and 24 h time points, respectively. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation revealed that the differentially expressed genes (DEGs) were highly enriched in hormone- and reactive oxygen species-related biological processes, including “response to oxidative stress or abiotic stimulus,” “peroxidase activity,” “regulation of transcription,” “hormone synthetic and metabolic process,” “hormone signal transduction,” “antioxidant activity,” and “transcription factor activity.” Moreover, K-means clustering demonstrated that DEGs (total RPKM value>12 from four time points) could be categorized into four kinds of expression trends: quick up/down over 6 or 12 h, and slow up/down over 24 h. Of these, DEGs involved in H2O2- and hormone- producing and signal-related genes were further enriched in this analysis, which indicated that the two kinds of small molecules, hormones and H2O2, play pivotal roles in the short-term salt stress response in poplar. This study provides a basis for future studies of the molecular adaptation of poplar and other tree species to salinity stress. PMID:26442002

  12. Comparative Analysis of the Secretome from a Model Filarial Nematode (Litomosoides sigmodontis) Reveals Maximal Diversity in Gravid Female Parasites*

    PubMed Central

    Armstrong, Stuart D.; Babayan, Simon A.; Lhermitte-Vallarino, Nathaly; Gray, Nick; Xia, Dong; Martin, Coralie; Kumar, Sujai; Taylor, David W.; Blaxter, Mark L.; Wastling, Jonathan M.; Makepeace, Benjamin L.

    2014-01-01

    Filarial nematodes (superfamily Filarioidea) are responsible for an annual global health burden of ∼6.3 million disability-adjusted life-years, which represents the greatest single component of morbidity attributable to helminths affecting humans. No vaccine exists for the major filarial diseases, lymphatic filariasis and onchocerciasis; in part because research on protective immunity against filariae has been constrained by the inability of the human-parasitic species to complete their lifecycles in laboratory mice. However, the rodent filaria Litomosoides sigmodontis has become a popular experimental model, as BALB/c mice are fully permissive for its development and reproduction. Here, we provide a comprehensive analysis of excretory-secretory products from L. sigmodontis across five lifecycle stages and identifications of host proteins associated with first-stage larvae (microfilariae) in the blood. Applying intensity-based quantification, we determined the abundance of 302 unique excretory-secretory proteins, of which 64.6% were present in quantifiable amounts only from gravid adult female nematodes. This lifecycle stage, together with immature microfilariae, released four proteins that have not previously been evaluated as vaccine candidates: a predicted 28.5 kDa filaria-specific protein, a zonadhesin and SCO-spondin-like protein, a vitellogenin, and a protein containing six metridin-like ShK toxin domains. Female nematodes also released two proteins derived from the obligate Wolbachia symbiont. Notably, excretory-secretory products from all parasite stages contained several uncharacterized members of the transthyretin-like protein family. Furthermore, biotin labeling revealed that redox proteins and enzymes involved in purinergic signaling were enriched on the adult nematode cuticle. Comparison of the L. sigmodontis adult secretome with that of the human-infective filarial nematode Brugia malayi (reported previously in three independent published studies

  13. Experimental investigation and theoretical analysis of pulse repetition rate adjustable deep ultraviolet picosecond radiation by second harmonic generation in KBe2BO3F2

    NASA Astrophysics Data System (ADS)

    Xu, Zhi; Zhang, Fengfeng; Zhang, Shenjin; Wang, Zhimin; Yang, Feng; Xu, Fengliang; Peng, Qinjun; Cui, Dafu; Zhang, Jingyuan; Wang, Xiaoyang; Chen, Chuangtian; Xu, Zuyan

    2014-06-01

    We reported on an experimental investigation and theoretical analysis of pulse repetition rate (PRR) adjustable deep ultraviolet (DUV) picosecond (ps) radiation by second harmonic generation (SHG) in KBe2BO3F2 (KBBF) crystal. Third harmonic radiation at 355 nm of a ps Nd:YVO4 laser output with PRR of 200 kHz-1 MHz was employed as the pump source. The dependence of the 177.3 nm output power on the 355 nm pump power was measured at different PRRs, and the maximum 177.3 nm average output power of 695 μW was obtained at the PRR of 200 kHz. The measured data agreed well with the results of the ps KBBF SHG theoretical simulations. Using simulations, the pulse width and the spectral bandwidth of the generated radiation at 177.3 nm were estimated to be 5.88 ps and 7.84 pm, respectively.

  14. CALORIMETER-BASED ADJUSTMENT OF MULTIPLICITY DETERMINED 240PU EFF KNOWN-A ANALYSIS FOR THE ASSAY OF PLUTONIUM

    SciTech Connect

    Dubose, F.

    2012-02-21

    In nuclear material processing facilities, it is often necessary to balance the competing demands of accuracy and throughput. While passive neutron multiplicity counting is the preferred method for relatively fast assays of plutonium, the presence of low-Z impurities (fluorine, beryllium, etc.) rapidly erodes the assay precision of passive neutron counting techniques, frequently resulting in unacceptably large total measurement uncertainties. Conversely, while calorimeters are immune to these impurity effects, the long count times required for high accuracy can be a hindrance to efficiency. The higher uncertainties in passive neutron measurements of impure material are driven by the resulting large (>>2) {alpha}-values, defined as the ({alpha},n):spontaneous fission neutron emission ratio. To counter impurity impacts for high-{alpha} materials, a known-{alpha} approach may be adopted. In this method, {alpha} is determined for a single item using a combination of gamma-ray and calorimetric measurements. Because calorimetry is based on heat output, rather than a statistical distribution of emitted neutrons, an {alpha}-value determined in this way is far more accurate than one determined from passive neutron counts. This fixed {alpha} value can be used in conventional multiplicity analysis for any plutonium-bearing item having the same chemical composition and isotopic distribution as the original. With the results of single calorimeter/passive neutron/gamma-ray measurement, these subsequent items can then be assayed with high precision and accuracy in a relatively short time, despite the presence of impurities. A calorimeter-based known-{alpha} multiplicity analysis technique is especially useful when requiring rapid, high accuracy, high precision measurements of multiple plutonium bearing items having a common source. The technique has therefore found numerous applications at the Savannah River Site. In each case, a plutonium (or mixed U/Pu) bearing item is divided

  15. Multichannel Detrended Fluctuation Analysis Reveals Synchronized Patterns of Spontaneous Spinal Activity in Anesthetized Cats

    PubMed Central

    Rodríguez, Erika E.; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A.; Jiménez, Ismael; Rudomín, Pablo

    2011-01-01

    The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA- mean = 1.040.09) or simultaneously from several lumbar segments (mDFA- mean = 1.010.06), where  = 0.5 indicates randomness while 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA- = 0.992 as compared to initial conditions mDFA- = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA- = 0.924). In contrast to the classical methods, such as correlation

  16. Multichannel detrended fluctuation analysis reveals synchronized patterns of spontaneous spinal activity in anesthetized cats.

    PubMed

    Rodríguez, Erika E; Hernández-Lemus, Enrique; Itzá-Ortiz, Benjamín A; Jiménez, Ismael; Rudomín, Pablo

    2011-01-01

    The analysis of the interaction and synchronization of relatively large ensembles of neurons is fundamental for the understanding of complex functions of the nervous system. It is known that the temporal synchronization of neural ensembles is involved in the generation of specific motor, sensory or cognitive processes. Also, the intersegmental coherence of spinal spontaneous activity may indicate the existence of synaptic neural pathways between different pairs of lumbar segments. In this study we present a multichannel version of the detrended fluctuation analysis method (mDFA) to analyze the correlation dynamics of spontaneous spinal activity (SSA) from time series analysis. This method together with the classical detrended fluctuation analysis (DFA) were used to find out whether the SSA recorded in one or several segments in the spinal cord of the anesthetized cat occurs either in a random or in an organized manner. Our results are consistent with a non-random organization of the sets of neurons involved in the generation of spontaneous cord dorsum potentials (CDPs) recorded either from one lumbar segment (DFA-α mean = 1.04[Formula: see text]0.09) or simultaneously from several lumbar segments (mDFA-α mean = 1.01[Formula: see text]0.06), where α = 0.5 indicates randomness while α = 0.5 indicates long-term correlations. To test the sensitivity of the mDFA method we also examined the effects of small spinal lesions aimed to partially interrupt connectivity between neighboring lumbosacral segments. We found that the synchronization and correlation between the CDPs recorded from the L5 and L6 segments in both sides of the spinal cord were reduced when a lesion comprising the left dorsal quadrant was performed between the segments L5 and L6 (mDFA-[Formula: see text] = 0.992 as compared to initial conditions mDFA-α = 1.186). The synchronization and correlation were reduced even further after a similar additional right spinal lesion (mDFA-α = 0.924). In contrast

  17. Analysis of gene expression during parabolic flights reveals distinct early gravity responses in Arabidopsis roots.

    PubMed

    Aubry-Hivet, D; Nziengui, H; Rapp, K; Oliveira, O; Paponov, I A; Li, Y; Hauslage, J; Vagt, N; Braun, M; Ditengou, F A; Dovzhenko, A; Palme, K

    2014-01-01

    Plant roots are among most intensively studied biological systems in gravity research. Altered gravity induces asymmetric cell growth leading to root bending. Differential distribution of the phytohormone auxin underlies root responses to gravity, being coordinated by auxin efflux transporters from the PIN family. The objective of this study was to compare early transcriptomic changes in roots of Arabidopsis thaliana wild type, and pin2 and pin3 mutants under parabolic flight conditions and to correlate these changes to auxin distribution. Parabolic flights allow comparison of transient 1-g, hypergravity and microgravity effects in living organisms in parallel. We found common and mutation-related genes differentially expressed in response to transient microgravity phases. Gene ontology analysis of common genes revealed lipid metabolism, response to stress factors and light categories as primarily involved in response to transient microgravity phases, suggesting that fundamental reorganisation of metabolic pathways functions upstream of a further signal mediating hormonal network. Gene expression changes in roots lacking the columella-located PIN3 were stronger than in those deprived of the epidermis and cortex cell-specific PIN2. Moreover, repetitive exposure to microgravity/hypergravity and gravity/hypergravity flight phases induced an up-regulation of auxin responsive genes in wild type and pin2 roots, but not in pin3 roots, suggesting a critical function of PIN3 in mediating auxin fluxes in response to transient microgravity phases. Our study provides important insights towards understanding signal transduction processes in transient microgravity conditions by combining for the first time the parabolic flight platform with the transcriptome analysis of different genetic mutants in the model plant, Arabidopsis.

  18. Comparative genomic analysis of clinical and environmental Vibrio vulnificus isolates revealed biotype 3 evolutionary relationships

    PubMed Central

    Koton, Yael; Gordon, Michal; Chalifa-Caspi, Vered; Bisharat, Naiel

    2015-01-01

    In 1996 a common-source outbreak of severe soft tissue and bloodstream infections erupted among Israeli fish farmers and fish consumers due to changes in fish marketing policies. The causative pathogen was a new strain of Vibrio vulnificus, named biotype 3, which displayed a unique biochemical and genotypic profile. Initial observations suggested that the pathogen erupted as a result of genetic recombination between two distinct populations. We applied a whole genome shotgun sequencing approach using several V. vulnificus strains from Israel in order to study the pan genome of V. vulnificus and determine the phylogenetic relationship of biotype 3 with existing populations. The core genome of V. vulnificus based on 16 draft and complete genomes consisted of 3068 genes, representing between 59 and 78% of the whole genome of 16 strains. The accessory genome varied in size from 781 to 2044 kbp. Phylogenetic analysis based on whole, core, and accessory genomes displayed similar clustering patterns with two main clusters, clinical (C) and environmental (E), all biotype 3 strains formed a distinct group within the E cluster. Annotation of accessory genomic regions found in biotype 3 strains and absent from the core genome yielded 1732 genes, of which the vast majority encoded hypothetical proteins, phage-related proteins, and mobile element proteins. A total of 1916 proteins (including 713 hypothetical proteins) were present in all human pathogenic strains (both biotype 3 and non-biotype 3) and absent from the environmental strains. Clustering analysis of the non-hypothetical proteins revealed 148 protein clusters shared by all human pathogenic strains; these included transcriptional regulators, arylsulfatases, methyl-accepting chemotaxis proteins, acetyltransferases, GGDEF family proteins, transposases, type IV secretory system (T4SS) proteins, and integrases. Our study showed that V. vulnificus biotype 3 evolved from environmental populations and formed a genetically

  19. Functional analysis of environmental DNA-derived type II polyketide synthases reveals structurally diverse secondary metabolites

    PubMed Central

    Feng, Zhiyang; Kallifidas, Dimitris; Brady, Sean F.

    2011-01-01

    A single gram of soil is predicted to contain thousands of unique bacterial species. The majority of these species remain recalcitrant to standard culture methods, prohibiting their use as sources of unique bioactive small molecules. The cloning and analysis of DNA extracted directly from environmental samples (environmental DNA, eDNA) provides a means of exploring the biosynthetic capacity of natural bacterial populations. Environmental DNA libraries contain large reservoirs of bacterial genetic diversity from which new secondary metabolite gene clusters can be systematically recovered and studied. The identification and heterologous expression of type II polyketide synthase-containing eDNA clones is reported here. Functional analysis of three soil DNA-derived polyketide synthase systems in Streptomyces albus revealed diverse metabolites belonging to well-known, rare, and previously uncharacterized structural families. The first of these systems is predicted to encode the production of the known antibiotic landomycin E. The second was found to encode the production of a metabolite with a previously uncharacterized pentacyclic ring system. The third was found to encode the production of unique KB-3346-5 derivatives, which show activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis. These results, together with those of other small-molecule-directed metagenomic studies, suggest that culture-independent approaches are capable of accessing biosynthetic diversity that has not yet been extensively explored using culture-based methods. The large-scale functional screening of eDNA clones should be a productive strategy for generating structurally previously uncharacterized chemical entities for use in future drug development efforts. PMID:21768346

  20. Comorbid Analysis of Genes Associated with Autism Spectrum Disorders Reveals Differential Evolutionary Constraints

    PubMed Central

    David, Maude M.; Enard, David; Ozturk, Alp; Daniels, Jena; Jung, Jae-Yoon; Diaz-Beltran, Leticia; Wall, Dennis. P.

    2016-01-01

    The burden of comorbidity in Autism Spectrum Disorder (ASD) is substantial. The symptoms of autism overlap with many other human conditions, reflecting common molecular pathologies suggesting that cross-disorder analysis will help prioritize autism gene candidates. Genes in the intersection between autism and related conditions may represent nonspecific indicators of dysregulation while genes unique to autism may play a more causal role. Thorough literature review allowed us to extract 125 ICD-9 codes comorbid to ASD that we mapped to 30 specific human disorders. In the present work, we performed an automated extraction of genes associated with ASD and its comorbid disorders, and found 1031 genes involved in ASD, among which 262 are involved in ASD only, with the remaining 779 involved in ASD and at least one comorbid disorder. A pathway analysis revealed 13 pathways not involved in any other comorbid disorders and therefore unique to ASD, all associated with basal cellular functions. These pathways differ from the pathways associated with both ASD and its comorbid conditions, with the latter being more specific to neural function. To determine whether the sequence of these genes have been subjected to differential evolutionary constraints, we studied long term constraints by looking into Genomic Evolutionary Rate Profiling, and showed that genes involved in several comorbid disorders seem to have undergone more purifying selection than the genes involved in ASD only. This result was corroborated by a higher dN/dS ratio for genes unique to ASD as compare to those that are shared between ASD and its comorbid disorders. Short-term evolutionary constraints showed the same trend as the pN/pS ratio indicates that genes unique to ASD were under significantly less evolutionary constraint than the genes associated with all other disorders. PMID:27414027

  1. Interspecies insertion polymorphism analysis reveals recent activity of transposable elements in extant coelacanths.

    PubMed

    Naville, Magali; Chalopin, Domitille; Volff, Jean-Nicolas

    2014-01-01

    Coelacanths are lobe-finned fish represented by two extant species, Latimeria chalumnae in South Africa and Comoros and L. menadoensis in Indonesia. Due to their intermediate phylogenetic position between ray-finned fish and tetrapods in the vertebrate lineage, they are of great interest from an evolutionary point of view. In addition, extant specimens look similar to 300 million-year-old fossils; because of their apparent slowly evolving morphology, coelacanths have been often described as « living fossils ». As an underlying cause of such a morphological stasis, several authors have proposed a slow evolution of the coelacanth genome. Accordingly, sequencing of the L. chalumnae genome has revealed a globally low substitution rate for protein-coding regions compared to other vertebrates. However, genome and gene evolution can also be influenced by transposable elements, which form a major and dynamic part of vertebrate genomes through their ability to move, duplicate and recombine. In this work, we have searched for evidence of transposition activity in coelacanth genomes through the comparative analysis of orthologous genomic regions from both Latimeria species. Comparison of 5.7 Mb (0.2%) of the L. chalumnae genome with orthologous Bacterial Artificial Chromosome clones from L. menadoensis allowed the identification of 27 species-specific transposable element insertions, with a strong relative contribution of CR1 non-LTR retrotransposons. Species-specific homologous recombination between the long terminal repeats of a new coelacanth endogenous retrovirus was also detected. Our analysis suggests that transposon activity is responsible for at least 0.6% of genome divergence between both Latimeria species. Taken together, this study demonstrates that coelacanth genomes are not evolutionary inert: they contain recently active transposable elements, which have significantly contributed to post-speciation genome divergence in Latimeria.

  2. Single cell analysis reveals gametic and tissue-specific instability of the SCA1 CAG repeat

    SciTech Connect

    Chong, S.S.; McCall, A.E.; Cota, J.

    1994-09-01

    Spinocerebellar ataxia type 1 is an autosomal dominant neurodegenerative disease caused by expansion of a CAG trinucleotide repeat within the SCA1 gene on chromosome 6p22-23. We performed a comparative analysis of the SCA1 CAG repeat from blood and sperm of an affected male. Genomic amplification revealed a broader smear of the SCA1 allele product from sperm compared to that from peripheral blood leukocytes (PBL). To resolve this observed difference, we analyzed single sperm directly and demonstrate that the SCA1 allele in PBL is also heterogeneous, although the range of variability in allele sizes is much less than that observed in sperm. Limited genome analysis was also performed on PBL DNA from an unaffected individual with an upper normal allele of 36 repeats in parallel with an affected individual with an expanded allele of 40 repeats. The 36 repeat normal allele, which contains a CAT interruption, was completely stable compared to the uninterrupted repeat of the SCA1 allele, demonstrating a direct correlation between absence of a CAT interruption and somatic instability of the repeat. We also analyzed the size of the CAG repeat in tissues derived from various brain regions from a patient with juvenile-onset disease to determine if the size of the expansion correlated with the site of neuropathology. The results clearly show tissue-specific differences in mosaicism of repeat length. More importantly, the pattern of tissue-specific differences in repeat-length mosaicism in SCA1 within the brain parallels those seen in Huntington disease. In both disorders the expanded alleles are smaller in cerebellar tissue. These results suggest that the observed tissue-specific differences in instability of the SCA1 CAG repeat, either within the brain or between blood and sperm, are a function of the intracellular milieu or the intrinsic replicative potential of the various celltypes.

  3. Duplication and differentiation of common carp (Cyprinus carpio) myoglobin genes revealed by BAC analysis.

    PubMed

    Zhao, Zi-Xia; Xu, Peng; Cao, Ding-Chen; Kuang, You-Yi; Deng, Hai-Xia; Zhang, Yan; Xu, Li-Ming; Li, Jiong-Tang; Xu, Jian; Sun, Xiao-Wen

    2014-09-15

    Two distinct myoglobin (mb) transcripts have been reported in common carp, Cyprinus carpio, which is a hypoxia-tolerant fish living in habitats with greatly fluctuant dissolved oxygen levels. Recombinant protein analysis has shown functional specialization of the two mb transcripts. In this work, analysis for mb-containing bacterial artificial chromosome (BAC) clones indicated different genome loci for common carp myoglobin-1 (mb-1) and myoglobin-2 (mb-2) genes. Fluorescence in situ hybridization (FISH) revealed that mb-1 and mb-2 are located on separate chromosomes. In both of the mb-1 and mb-2 containing BAC clones, gene synteny was well conserved with the homologous region on zebrafish chromosome 1, supporting that the common carp specific mb-2 gene originated from the recent whole genome duplication event in cyprinid lineage. Transcription factor binding sites search indicated that both common carp mb genes lacked specificity Protein 1 (Sp1) and myocyte enhancer factor-2 (MEF2) binding sites, which mediated muscle-specific and calcium-dependent expression in the well-studied mb promoters. Potential hypoxia response elements (HREs) were predicted in the regulatory region of common carp mb genes. These characteristics of common carp mb gene regulatory region well interpreted the hypoxia-inducible, non-muscle expression pattern of mb-1. In the case of mb-2, a 10 bp insertion to the binding site of upstream stimulatory factor (USF), which was a co-factor of hypoxia inducible factor (HIF), might cause the non-response to hypoxia treatment of mb-2. The case of common carp mb gene duplication and subsequent differentiation in expression pattern and protein function provided an example for adaptive evolution toward aquatic hypoxia tolerance.

  4. Revealing Shared and Distinct Gene Network Organization in Arabidopsis Immune Responses by Integrative Analysis1

    PubMed Central

    Dong, Xiaobao; Jiang, Zhenhong; Peng, You-Liang; Zhang, Ziding

    2015-01-01

    Pattern-triggered immunity (PTI) and effector-triggered immunity (ETI) are two main plant immune responses to counter pathogen invasion. Genome-wide gene network organizing principles leading to quantitative differences between PTI and ETI have remained elusive. We combined an advanced machine learning method and modular network analysis to systematically characterize the organizing principles of Arabidopsis (Arabidopsis thaliana) PTI and ETI at three network resolutions. At the single network node/edge level, we ranked genes and gene interactions based on their ability to distinguish immune response from normal growth and successfully identified many immune-related genes associated with PTI and ETI. Topological analysis revealed that the top-ranked gene interactions tend to link network modules. At the subnetwork level, we identified a subnetwork shared by PTI and ETI encompassing 1,159 genes and 1,289 interactions. This subnetwork is enriched in interactions linking network modules and is also a hotspot of attack by pathogen effectors. The subnetwork likely represents a core component in the coordination of multiple biological processes to favor defense over development. Finally, we constructed modular network models for PTI and ETI to explain the quantitative differences in the global network architecture. Our results indicate that the defense modules in ETI are organized into relatively independent structures, explaining the robustness of ETI to genetic mutations and effector attacks. Taken together, the multiscale comparisons of PTI and ETI provide a systems biology perspective on plant immunity and emphasize coordination among network modules to establish a robust immune response. PMID:25614062

  5. A secretomics analysis reveals major differences in the macrophage responses towards different types of carbon nanotubes.

    PubMed

    Palomäki, Jaana; Sund, Jukka; Vippola, Minnamari; Kinaret, Pia; Greco, Dario; Savolainen, Kai; Puustinen, Anne; Alenius, Harri

    2015-01-01

    Certain types of carbon nanotubes (CNT) can evoke inflammation, fibrosis and mesothelioma in vivo, raising concerns about their potential health effects. It has been recently postulated that NLRP3 inflammasome activation is important in the CNT-induced toxicity. However, more comprehensive studies of the protein secretion induced by CNT can provide new information about their possible pathogenic mechanisms. Here, we studied protein secretion from human macrophages with a proteomic approach in an unbiased way. Human monocyte-derived macrophages (MDM) were exposed to tangled or rigid, long multi-walled CNT (MWCNT) or crocidolite asbestos for 6 h. The growth media was concentrated and secreted proteins were analyzed using 2D-DIGE and DeCyder software. Subsequently, significantly up- or down-regulated protein spots were in-gel digested and identified with an LC-MS/MS approach. Bioinformatics analysis was performed to reveal the different patterns of protein secretion induced by these materials. The results show that both long rigid MWCNT and asbestos elicited ample and highly similar protein secretion. In contrast, exposure to long tangled MWCNT induced weaker protein secretion with a more distinct profile. Secretion of lysosomal proteins followed the exposure to all materials, suggesting lysosomal damage. However, only long rigid MWCNT was associated with apoptosis. This analysis suggests that the CNT toxicity in human MDM is mediated via vigorous secretion of inflammation-related proteins and apoptosis. This study provides new insights into the mechanisms of toxicity of high aspect ratio nanomaterials and indicates that not all types of CNT are as hazardous as asbestos fibers.

  6. Global transcriptomic analysis of Cyanothece 51142 reveals robust diurnal oscillation of central metabolic processes.

    PubMed

    Stöckel, Jana; Welsh, Eric A; Liberton, Michelle; Kunnvakkam, Rangesh; Aurora, Rajeev; Pakrasi, Himadri B

    2008-04-22

    Cyanobacteria are photosynthetic organisms and are the only prokaryotes known to have a circadian lifestyle. Unicellular diazotrophic cyanobacteria such as Cyanothece sp. ATCC 51142 produce oxygen and can also fix atmospheric nitrogen, a process exquisitely sensitive to oxygen. To accommodate such antagonistic processes, the intracellular environment of Cyanothece oscillates between aerobic and anaerobic conditions during a day-night cycle. This is accomplished by temporal separation of the two processes: photosynthesis during the day and nitrogen fixation at night. Although previous studies have examined periodic changes in transcript levels for a limited number of genes in Cyanothece and other unicellular diazotrophic cyanobacteria, a comprehensive study of transcriptional activity in a nitrogen-fixing cyanobacterium is necessary to understand the impact of the temporal separation of photosynthesis and nitrogen fixation on global gene regulation and cellular metabolism. We have examined the expression patterns of nearly 5,000 genes in Cyanothece 51142 during two consecutive diurnal periods. Our analysis showed that approximately 30% of these genes exhibited robust oscillating expression profiles. Interestingly, this set included genes for almost all central metabolic processes in Cyanothece 51142. A transcriptional network of all genes with significantly oscillating transcript levels revealed that the majority of genes encoding enzymes in numerous individual biochemical pathways, such as glycolysis, oxidative pentose phosphate pathway, and glycogen metabolism, were coregulated and maximally expressed at distinct phases during the diurnal cycle. These studies provide a comprehensive picture of how a physiologically relevant diurnal light-dark cycle influences the metabolism in a photosynthetic bacterium.

  7. Temporal analysis of mtDNA variation reveals decreased genetic diversity in least terns

    USGS Publications Warehouse

    Draheim, Hope M.; Baird, Patricia; Haig, Susan M.

    2012-01-01

    The Least Tern (Sternula antillarum) has undergone large population declines over the last century as a result of direct and indirect anthropogenic factors. The genetic implications of these declines are unknown. We used historical museum specimens (pre-1960) and contemporary (2001–2005) samples to examine range-wide phylogeographic patterns and investigate potential loss in the species' genetic variation. We obtained sequences (522 bp) of the mitochondrial gene for NADH dehydrogenase subunit 6 (ND6) from 268 individuals from across the species' range. Phylogeographic analysis revealed no association with geography or traditional subspecies designations. However, we detected potential reductions in genetic diversity in contemporary samples from California and the Atlantic coast Least Tern from that in historical samples, suggesting that current genetic diversity in Least Tern populations is lower than in their pre-1960 counterparts. Our results offer unique insights into changes in the Least Tern's genetic diversity over the past century and highlight the importance and utility of museum specimens in studies of conservation genetics.

  8. Global Phospholipidomics Analysis Reveals Selective Pulmonary Peroxidation Profiles Upon Inhalation of Single Walled Carbon Nanotubes

    PubMed Central

    Tyurina, Yulia Y.; Kisin, Elena R.; Murray, Ashley; Tyurin, Vladimir A.; Kapralova, Valentina I.; Sparvero, Louis J.; Amoscato, Andrew A.; Samhan-Arias, Alejandro K.; Swedin, Linda; Lahesmaa, Riitta; Fadeel, Bengt; Shvedova, Anna A.; Kagan, Valerian E.

    2011-01-01

    It is commonly believed that nanomaterials cause non-specific oxidative damage. Our mass spectrometry-based oxidative lipidomics analysis of all major phospholipid classes revealed highly selective patterns of pulmonary peroxidation after inhalation exposure of mice to single-walled carbon nanotubes. No oxidized molecular species were found in two most abundant phospholipid classes – phosphatidylcholine and phosphatidylethanolamine. Peroxidation products were identified in three relatively minor classes of anionic phospholipids, cardiolipin, phosphatidylserine and phosphatidylinositol whereby oxygenation of polyunsaturated fatty acid residues also showed unusual substrate specificity. This non-random peroxidation coincided with the accumulation of apoptotic cells in the lung. A similar selective phospholipid peroxidation profile was detected upon incubation of a mixture of total lung lipids with H2O2/cytochrome c known to catalyze cardiolipin and phosphatidylserine peroxidation in apoptotic cells. The characterized specific phospholipid peroxidation signaling pathways indicate new approaches to the development of mitochondria targeted regulators of cardiolipin peroxidation to protect against deleterious effects of pro-apoptotic effects of single-walled carbon nanotubes in the lung. PMID:21800898

  9. Comparative Genomic Analysis Reveals Organization, Function and Evolution of ars Genes in Pantoea spp.

    PubMed Central

    Wang, Liying; Wang, Jin; Jing, Chuanyong

    2017-01-01

    Numerous genes are involved in various strategies to resist toxic arsenic (As). However, the As resistance strategy in genus Pantoea is poorly understood. In this study, a comparative genome analysis of 23 Pantoea genomes was conducted. Two vertical genetic arsC-like genes without any contribution to As resistance were found to exist in the 23 Pantoea strains. Besides the two arsC-like genes, As resistance gene clusters arsRBC or arsRBCH were found in 15 Pantoea genomes. These ars clusters were found to be acquired by horizontal gene transfer (HGT) from sources related to Franconibacter helveticus, Serratia marcescens, and Citrobacter freundii. During the history of evolution, the ars clusters were acquired more than once in some species, and were lost in some strains, producing strains without As resistance capability. This study revealed the organization, distribution and the complex evolutionary history of As resistance genes in Pantoea spp.. The insights gained in this study improved our understanding on the As resistance strategy of Pantoea spp. and its roles in the biogeochemical cycling of As. PMID:28377759

  10. What does population structure analysis reveal about the Pterostylis longifolia complex (Orchidaceae)?

    PubMed Central

    Janes, Jasmine K; Steane, Dorothy A; Vaillancourt, René E

    2012-01-01

    Morphologically similar groups of species are common and pose significant challenges for taxonomists. Differences in approaches to classifying unique species can result in some species being overlooked, whereas others are wrongly conserved. The genetic diversity and population structure of the Pterostylis longifolia complex (Orchidaceae) in Tasmania was investigated to determine if four species, and potential hybrids, could be distinguished through genomic AFLP and chloroplast restriction-fragment-length polymorphism (RFLP) markers. Analysis of molecular variance (AMOVA) results indicated that little genetic variation was present among taxa, whereas PCoA analyses revealed genetic variation at a regional scale irrespective of taxa. Population genetic structure analyses identified three clusters that correspond to regional genetic and single taxon-specific phenotypic variation. The results from this study suggest that “longifolia” species have persisted throughout the last glacial maximum in Tasmania and that the complex may be best treated as a single taxon with several morphotypes. These results could have serious evolutionary and conservation implications as taxonomic changes could result in the instatement of a single, widespread taxon in which rarer morphotypes are not protected. PMID:23170201

  11. Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

    PubMed Central

    Caulin, Aleah F.; Graham, Trevor A.; Wang, Li-San; Maley, Carlo C.

    2015-01-01

    Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. We surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans. PMID:26056366

  12. Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

    SciTech Connect

    Caulin, Aleah F.; Graham, Trevor A.; Wang, Li-San; Maley, Carlo C.

    2015-06-08

    Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer risk to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. Also, we surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Lastly, exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.

  13. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    PubMed Central

    Yang, Yunlai; Arouri, Khaled

    2016-01-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations. PMID:26965479

  14. Genomewide analysis of Drosophila GAGA factor target genes reveals context-dependent DNA binding

    PubMed Central

    van Steensel, Bas; Delrow, Jeffrey; Bussemaker, Harmen J.

    2003-01-01

    The association of sequence-specific DNA-binding factors with their cognate target sequences in vivo depends on the local molecular context, yet this context is poorly understood. To address this issue, we have performed genomewide mapping of in vivo target genes of Drosophila GAGA factor (GAF). The resulting list of ≈250 target genes indicates that GAF regulates many cellular pathways. We applied unbiased motif-based regression analysis to identify the sequence context that determines GAF binding. Our results confirm that GAF selectively associates with (GA)n repeat elements in vivo. GAF binding occurs in upstream regulatory regions, but less in downstream regions. Surprisingly, GAF binds abundantly to introns but is virtually absent from exons, even though the density of (GA)n is roughly the same. Intron binding occurs equally frequently in last introns compared with first introns, suggesting that GAF may not only regulate transcription initiation, but possibly also elongation. We provide evidence for cooperative binding of GAF to closely spaced (GA)n elements and explain the lack of GAF binding to exons by the absence of such closely spaced GA repeats. Our approach for revealing determinants of context-dependent DNA binding will be applicable to many other transcription factors. PMID:12601174

  15. Transcriptomic Analysis Reveals Significant B Lymphocyte Suppression in Corticosteroid-Treated Hosts with Pneumocystis Pneumonia.

    PubMed

    Hu, Yang; Wang, Dong; Zhai, Kan; Tong, Zhaohui

    2017-03-01

    Pneumocystis pneumonia (PCP) is an opportunistic, infectious disease that is prevalent in immunosuppressed hosts. Corticosteroid treatment is the most significant risk factor for patients with PCP who are human immunodeficiency virus negative, although little is known about how corticosteroids alter the host defense against Pneumocystis infection. In the present study, we used transcriptome analysis to examine the immune response in the lungs of corticosteroid-treated PCP mice. The results showed down-regulation in the genes related to both native immunity, such as antigen processing and presentation, inflammatory response, and phagocytosis, as well as B and T lymphocyte immunity. The repression of gene expression, corresponding to B cell immunity, including B cell signaling, homeostasis, and Ig production, was prominent. The finding was confirmed by quantitative PCR of mouse lungs and the peripheral blood of patients with PCP. Flow cytometry also revealed a significant depletion of B cells in corticosteroid-treated PCP mice. Our study has highlighted that corticosteroid treatment suppresses the B cell immunity in the PCP host, which is likely one of the main reasons that corticosteroid treatment may stimulate PCP development.

  16. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis

    PubMed Central

    Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; XI, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

    2016-01-01

    The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian’s gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment. PMID:27708392

  17. Comprehensive Tissue-Specific Transcriptome Analysis Reveals Distinct Regulatory Programs during Early Tomato Fruit Development.

    PubMed

    Pattison, Richard J; Csukasi, Fabiana; Zheng, Yi; Fei, Zhangjun; van der Knaap, Esther; Catalá, Carmen

    2015-08-01

    Fruit formation and early development involve a range of physiological and morphological transformations of the various constituent tissues of the ovary. These developmental changes vary considerably according to tissue type, but molecular analyses at an organ-wide level inevitably obscure many tissue-specific phenomena. We used laser-capture microdissection coupled to high-throughput RNA sequencing to analyze the transcriptome of ovaries and fruit tissues of the wild tomato species Solanum pimpinellifolium. This laser-capture microdissection-high-throughput RNA sequencing approach allowed quantitative global profiling of gene expression at previously unobtainable levels of spatial resolution, revealing numerous contrasting transcriptome profiles and uncovering rare and cell type-specific transcripts. Coexpressed gene clusters linked specific tissues and stages to major transcriptional changes underlying the ovary-to-fruit transition and provided evidence of regulatory modules related to cell division, photosynthesis, and auxin transport in internal fruit tissues, together with parallel specialization of the pericarp transcriptome in stress responses and secondary metabolism. Analysis of transcription factor expression and regulatory motifs indicated putative gene regulatory modules that may regulate the development of different tissues and hormonal processes. Major alterations in the expression of hormone metabolic and signaling components illustrate the complex hormonal control underpinning fruit formation, with intricate spatiotemporal variations suggesting separate regulatory programs.

  18. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways

    PubMed Central

    Jiang, Lulu; Hindmarch, Charles C. T.; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W.; Welsh, Gavin I.

    2016-01-01

    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or ‘podocytes’, the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes. PMID:27774996

  19. Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

    PubMed

    Hoadley, Katherine A; Yau, Christina; Wolf, Denise M; Cherniack, Andrew D; Tamborero, David; Ng, Sam; Leiserson, Max D M; Niu, Beifang; McLellan, Michael D; Uzunangelov, Vladislav; Zhang, Jiashan; Kandoth, Cyriac; Akbani, Rehan; Shen, Hui; Omberg, Larsson; Chu, Andy; Margolin, Adam A; Van't Veer, Laura J; Lopez-Bigas, Nuria; Laird, Peter W; Raphael, Benjamin J; Ding, Li; Robertson, A Gordon; Byers, Lauren A; Mills, Gordon B; Weinstein, John N; Van Waes, Carter; Chen, Zhong; Collisson, Eric A; Benz, Christopher C; Perou, Charles M; Stuart, Joshua M

    2014-08-14

    Recent genomic analyses of pathologically defined tumor types identify "within-a-tissue" disease subtypes. However, the extent to which genomic signatures are shared across tissues is still unclear. We performed an integrative analysis using five genome-wide platforms and one proteomic platform on 3,527 specimens from 12 cancer types, revealing a unified classification into 11 major subtypes. Five subtypes were nearly identical to their tissue-of-origin counterparts, but several distinct cancer types were found to converge into common subtypes. Lung squamous, head and neck, and a subset of bladder cancers coalesced into one subtype typified by TP53 alterations, TP63 amplifications, and high expression of immune and proliferation pathway genes. Of note, bladder cancers split into three pan-cancer subtypes. The multiplatform classification, while correlated with tissue-of-origin, provides independent information for predicting clinical outcomes. All data sets are available for data-mining from a unified resource to support further biological discoveries and insights into novel therapeutic strategies.

  20. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    PubMed Central

    2010-01-01

    Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements. PMID:21044362

  1. Unique Features of Ethnic Mongolian Gut Microbiome revealed by metagenomic analysis.

    PubMed

    Liu, Wenjun; Zhang, Jiachao; Wu, Chunyan; Cai, Shunfeng; Huang, Weiqiang; Chen, Jing; Xi, Xiaoxia; Liang, Zebin; Hou, Qiangchuan; Zhou, Bing; Qin, Nan; Zhang, Heping

    2016-10-06

    The human gut microbiota varies considerably among world populations due to a variety of factors including genetic background, diet, cultural habits and socioeconomic status. Here we characterized 110 healthy Mongolian adults gut microbiota by shotgun metagenomic sequencing and compared the intestinal microbiome among Mongolians, the Hans and European cohorts. The results showed that the taxonomic profile of intestinal microbiome among cohorts revealed the Actinobaceria and Bifidobacterium were the key microbes contributing to the differences among Mongolians, the Hans and Europeans at the phylum level and genus level, respectively. Metagenomic species analysis indicated that Faecalibacterium prausnitzii and Coprococcus comeswere enrich in Mongolian people which might contribute to gut health through anti-inflammatory properties and butyrate production, respectively. On the other hand, the enriched genus Collinsella, biomarker in symptomatic atherosclerosis patients, might be associated with the high morbidity of cardiovascular and cerebrovascular diseases in Mongolian adults. At the functional level, a unique microbial metabolic pathway profile was present in Mongolian's gut which mainly distributed in amino acid metabolism, carbohydrate metabolism, energy metabolism, lipid metabolism, glycan biosynthesis and metabolism. We can attribute the specific signatures of Mongolian gut microbiome to their unique genotype, dietary habits and living environment.

  2. Comparative genomic analysis of Lactobacillus plantarum ZJ316 reveals its genetic adaptation and potential probiotic profiles* #

    PubMed Central

    Li, Ping; Li, Xuan; Gu, Qing; Lou, Xiu-yu; Zhang, Xiao-mei; Song, Da-feng; Zhang, Chen

    2016-01-01

    Objective: In previous studies, Lactobacillus plantarum ZJ316 showed probiotic properties, such as antimicrobial activity against various pathogens and the capacity to significantly improve pig growth and pork quality. The purpose of this study was to reveal the genes potentially related to its genetic adaptation and probiotic profiles based on comparative genomic analysis. Methods: The genome sequence of L. plantarum ZJ316 was compared with those of eight L. plantarum strains deposited in GenBank. BLASTN, Mauve, and MUMmer programs were used for genome alignment and comparison. CRISPRFinder was applied for searching the clustered regularly interspaced short palindromic repeats (CRISPRs). Results: We identified genes that encode proteins related to genetic adaptation and probiotic profiles, including carbohydrate transport and metabolism, proteolytic enzyme systems and amino acid biosynthesis, CRISPR adaptive immunity, stress responses, bile salt resistance, ability to adhere to the host intestinal wall, exopolysaccharide (EPS) biosynthesis, and bacteriocin biosynthesis. Conclusions: Comparative characterization of the L. plantarum ZJ316 genome provided the genetic basis for further elucidating the functional mechanisms of its probiotic properties. ZJ316 could be considered a potential probiotic candidate. PMID:27487802

  3. GC--MS analysis reveals production of 2--Phenylethanol from Aspergillus niger endophytic in rose.

    PubMed

    Wani, Masood Ahmed; Sanjana, Kaul; Kumar, Dhar Manoj; Lal, Dhar Kanahya

    2010-02-01

    Endophytes include all organisms that during a variable period of their life, colonize the living internal tissues of their hosts without causing detectable symptoms. Several fungal endophytes have been isolated from a variety of plant species which have proved themselves as a rich source of secondary metabolites. The reported natural products from endophytes include antibiotics, immunosuppresants, anticancer compounds, antioxidant agents, etc. For the first time Rosa damacaena (rose) has been explored for its endophytes. The rose oil industry is the major identified deligence for its application in perfumery, flavouring, ointments, and pharmaceuticals including various herbal products. During the present investigation fungal endophytes were isolated from Rosa damacaena. A total of fifty four isolates were isolated out of which sixteen isolates were screened for the production of secondary metabolites. GCMS analysis reveals the production of 2-phenylethanol by one of the isolates JUBT 3M which was identified as Aspergillus niger. This is the first report of production of 2-phenylethanol from endophytic A. niger. 2-phenylethanol is an important constituent of rose oil constituting about 4.06% of rose oil. Presence of 2-phenylethanol indicates that the endophyte of rose may duplicate the biosynthesis of phenyl propanoids by rose plant. Besides this, the other commercial applications of phenylethanol include its use in antiseptics, disinfectants, anti-microbials and preservative in pharmaceuticals.

  4. Phylum-specific environmental DNA analysis reveals remarkably high global biodiversity of Cercozoa (Protozoa).

    PubMed

    Bass, David; Cavalier-Smith, Thomas

    2004-11-01

    This study presents the first 18S rRNA multi-library environmental PCR survey of a single protozoan phylum, Cercozoa Cavalier-Smith 1998, from a range of different habitats. Phylogenetic analysis reveals at least nine novel clades within the phylum, several possibly at the level of order or above. Further experiments are described to ascertain the true ecological and geographical distributions of some clades that might be inferred from the tree to be restricted in either or both ways. These results suggest that the diversity of cercozoan taxa may run into thousands of lineages, making it comparable in diversity to the largest better-characterized protozoan phyla, e.g. Ciliophora (ciliates and suctorians) and Foraminifera. New sequences of cultured Spongomonas, Metromonas and Metopion are also presented. In the light of these additions, and the increased taxon sampling from the environmental libraries, some revisions of cercozoan classification are made: the transfer of Spongomonadea from Reticulofilosa to Monadofilosa; the removal of Metopiida from Sarcomonadea; and the creation of the new order Metromonadida, currently containing the single genus Metromonas. Although Metromonas groups with weak to moderate support with Chlorarachnea, it is here placed in superclass Monadofilosa, to which it is morphologically more similar.

  5. A pangenomic analysis of the Nannochloropsis organellar genomes reveals novel genetic variations in key metabolic genes

    PubMed Central

    2014-01-01

    Background Microalgae in the genus Nannochloropsis are photosynthetic marine Eustigmatophytes of significant interest to the bioenergy and aquaculture sectors due to their ability to efficiently accumulate biomass and lipids for utilization in renewable transportation fuels, aquaculture feed, and other useful bioproducts. To better understand the genetic complement that drives the metabolic processes of these organisms, we present the assembly and comparative pangenomic analysis of the chloroplast and mitochondrial genomes from Nannochloropsis salina CCMP1776. Results The chloroplast and mitochondrial genomes of N. salina are 98.4% and 97% identical to their counterparts in Nannochloropsis gaditana. Comparison of the Nannochloropsis pangenome to other algae within and outside of the same phyla revealed regions of significant genetic divergence in key genes that encode proteins needed for regulation of branched chain amino synthesis (acetohydroxyacid synthase), carbon fixation (RuBisCO activase), energy conservation (ATP synthase), protein synthesis and homeostasis (Clp protease, ribosome). Conclusions Many organellar gene modifications in Nannochloropsis are unique and deviate from conserved orthologs found across the tree of life. Implementation of secondary and tertiary structure prediction was crucial to functionally characterize many proteins and therefore should be implemented in automated annotation pipelines. The exceptional similarity of the N. salina and N. gaditana organellar genomes suggests that N. gaditana be reclassified as a strain of N. salina. PMID:24646409

  6. Solutions to Peto's paradox revealed by mathematical modelling and cross-species cancer gene analysis

    DOE PAGES

    Caulin, Aleah F.; Graham, Trevor A.; Wang, Li-San; ...

    2015-06-08

    Whales have 1000-fold more cells than humans and mice have 1000-fold fewer; however, cancer risk across species does not increase with the number of somatic cells and the lifespan of the organism. This observation is known as Peto's paradox. How much would evolution have to change the parameters of somatic evolution in order to equalize the cancer risk between species that differ by orders of magnitude in size? Analysis of previously published models of colorectal cancer suggests that a two- to three-fold decrease in the mutation rate or stem cell division rate is enough to reduce a whale's cancer riskmore » to that of a human. Similarly, the addition of one to two required tumour-suppressor gene mutations would also be sufficient. Also, we surveyed mammalian genomes and did not find a positive correlation of tumour-suppressor genes with increasing body mass and longevity. However, we found evidence of the amplification of TP53 in elephants, MAL in horses and FBXO31 in microbats, which might explain Peto's paradox in those species. Lastly, exploring parameters that evolution may have fine-tuned in large, long-lived organisms will help guide future experiments to reveal the underlying biology responsible for Peto's paradox and guide cancer prevention in humans.« less

  7. Analysis of the community structure of abyssal kinetoplastids revealed similar communities at larger spatial scales

    PubMed Central

    Salani, Faezeh Shah; Arndt, Hartmut; Hausmann, Klaus; Nitsche, Frank; Scheckenbach, Frank

    2012-01-01

    Knowledge of the spatial scales of diversity is necessary to evaluate the mechanisms driving biodiversity and biogeography in the vast but poorly understood deep sea. The community structure of kinetoplastids, an important group of microbial eukaryotes belonging to the Euglenozoa, from all abyssal plains of the South Atlantic and two areas of the eastern Mediterranean was studied using partial small subunit ribosomal DNA gene clone libraries. A total of 1364 clones from 10 different regions were retrieved. The analysis revealed statistically not distinguishable communities from both the South-East Atlantic (Angola and Guinea Basin) and the South-West Atlantic (Angola and Brazil Basin) at spatial scales of 1000–3000 km, whereas all other communities were significantly differentiated from one another. It seems likely that multiple processes operate at the same time to shape communities of deep-sea kinetoplastids. Nevertheless, constant and homogenous environmental conditions over large spatial scales at abyssal depths, together with high dispersal capabilities of microbial eukaryotes, maintain best the results of statistically indistinguishable communities at larger spatial scales. PMID:22071346

  8. Systems-level analysis reveals selective regulation of Aqp2 gene expression by vasopressin

    PubMed Central

    Sandoval, Pablo C.; Claxton, J’Neka S.; Lee, Jae Wook; Saeed, Fahad; Hoffert, Jason D.; Knepper, Mark A.

    2016-01-01

    Vasopressin-mediated regulation of renal water excretion is defective in a variety of water balance disorders in humans. It occurs in part through long-term mechanisms that regulate the abundance of the aquaporin-2 water channel in renal collecting duct cells. Here, we use deep DNA sequencing in mouse collecting duct cells to ask whether vasopressin signaling selectively increases Aqp2 gene transcription or whether it triggers a broadly targeted transcriptional network. ChIP-Seq quantification of binding sites for RNA polymerase II was combined with RNA-Seq quantification of transcript abundances to identify genes whose transcription is regulated by vasopressin. (View curated dataset at https://helixweb.nih.gov/ESBL/Database/Vasopressin/). The analysis revealed only 35 vasopressin-regulated genes (of 3659) including Aqp2. Increases in RNA polymerase II binding and mRNA abundances for Aqp2 far outstripped corresponding measurements for all other genes, consistent with the conclusion that vasopressin-mediated transcriptional regulation is highly selective for Aqp2. Despite the overall selectivity of the net transcriptional response, vasopressin treatment was associated with increased RNA polymerase II binding to the promoter proximal region of a majority of expressed genes, suggesting a nearly global positive regulation of transcriptional initiation with transcriptional pausing. Thus, the overall net selectivity appears to be a result of selective control of transcriptional elongation. PMID:27725713

  9. Genome-wide analysis reveals adaptation to high altitudes in Tibetan sheep

    PubMed Central

    Wei, Caihong; Wang, Huihua; Liu, Gang; Zhao, Fuping; Kijas, James W.; Ma, Youji; Lu, Jian; Zhang, Li; Cao, Jiaxue; Wu, Mingming; Wang, Guangkai; Liu, Ruizao; Liu, Zhen; Zhang, Shuzhen; Liu, Chousheng; Du, Lixin

    2016-01-01

    Tibetan sheep have lived on the Tibetan Plateau for thousands of years; however, the process and consequences of adaptation to this extreme environment have not been elucidated for important livestock such as sheep. Here, seven sheep breeds, representing both highland and lowland breeds from different areas of China, were genotyped for a genome-wide collection of single-nucleotide polymorphisms (SNPs). The FST and XP-EHH approaches were used to identify regions harbouring local positive selection between these highland and lowland breeds, and 236 genes were identified. We detected selection events spanning genes involved in angiogenesis, energy production and erythropoiesis. In particular, several candidate genes were associated with high-altitude hypoxia, including EPAS1, CRYAA, LONP1, NF1, DPP4, SOD1, PPARG and SOCS2. EPAS1 plays a crucial role in hypoxia adaption; therefore, we investigated the exon sequences of EPAS1 and identified 12 mutations. Analysis of the relationship between blood-related phenotypes and EPAS1 genotypes in additional highland sheep revealed that a homozygous mutation at a relatively conserved site in the EPAS1 3′ untranslated region was associated with increased mean corpuscular haemoglobin concentration and mean corpuscular volume. Taken together, our results provide evidence of the genetic diversity of highland sheep and indicate potential high-altitude hypoxia adaptation mechanisms, including the role of EPAS1 in adaptation. PMID:27230812

  10. Biometric variability of goat populations revealed by means of principal component analysis.

    PubMed

    Pires, Luanna Chácara; Machado, Théa M Medeiros; Araújo, Adriana Mello; Olson, Timothy A; da Silva, João Batista Lopes; Torres, Robledo Almeida; Costa, Márcio da Silva

    2012-12-01

    The aim was to analyze variation in 12 Brazilian and Moroccan goat populations, and, through principal component analysis (PCA), check the importance of body measures and their indices as a means of distinguishing among individuals and populations. The biometric measurements were wither height (WH), brisket height (BH) and ear length (EL). Thorax depth (WH-BH) and the three indices, TD/WH, EL/TD and EL/WH, were also calculated. Of the seven components extracted, the first three principal components were sufficient to explain 99.5% of the total variance of the data. Graphical dispersion by genetic groups revealed that European dairy breeds clustered together. The Moroccan breeds were separated into two groups, one comprising the Drâa and the other the Zagora and Rhâali breeds. Whereas, on the one side, the Anglo-Nubian and undefined breeds were the closest to one another the goats of the Azul were observed to have the highest variation of all the breeds. The Anglo-Nubian and Boer breeds were similar to each other. The Nambi-type goats remained distinct from all the other populations. In general, the use of graphical representation of PCA values allowed to distinguish genetic groups.

  11. Further analysis reveals new gut microbiome markers of type 2 diabetes mellitus.

    PubMed

    Wang, Xiaokai; Xu, Xiaoqiang; Xia, Yan

    2017-03-01

    In recent years, metagenome-wide association studies have revealed potential relationships between intestinal microbiomes and the pathogenesis of type 2 diabetes mellitus (T2DM). However, considering the increase in volume of gene catalogues and algorithms, an updated analysis would be expected to confirm previous discoveries and provide new knowledge. We therefore constructed new profiles after mapping the recent catalogue of reference genes in the human gut microbiome to reanalyze samples from T2DM cases and controls in the Chinese population. We identified different compositions between Chinese controls and T2DM patients at the species and genus levels, especially in the case of butyrate-producing bacteria, Haemophilus, and Lactobacillus. An effective metagenomic linkage group random forest model was built to differentiate controls from T2DM cases in different cohorts. Functional markers from the Kyoto Encyclopedia of Genes and Genomes database were identified using new annotations. We also report 16 virulence factor markers and 22 antibiotic resistance markers associated with T2DM.

  12. RNA sequencing analysis of human podocytes reveals glucocorticoid regulated gene networks targeting non-immune pathways.

    PubMed

    Jiang, Lulu; Hindmarch, Charles C T; Rogers, Mark; Campbell, Colin; Waterfall, Christy; Coghill, Jane; Mathieson, Peter W; Welsh, Gavin I

    2016-10-24

    Glucocorticoids are steroids that reduce inflammation and are used as immunosuppressive drugs for many diseases. They are also the mainstay for the treatment of minimal change nephropathy (MCN), which is characterised by an absence of inflammation. Their mechanisms of action remain elusive. Evidence suggests that immunomodulatory drugs can directly act on glomerular epithelial cells or 'podocytes', the cell type which is the main target of injury in MCN. To understand the nature of glucocorticoid effects on non-immune cell functions, we generated RNA sequencing data from human podocyte cell lines and identified the genes that are significantly regulated in dexamethasone-treated podocytes compared to vehicle-treated cells. The upregulated genes are of functional relevance to cytoskeleton-related processes, whereas the downregulated genes mostly encode pro-inflammatory cytokines and growth factors. We observed a tendency for dexamethasone-upregulated genes to be downregulated in MCN patients. Integrative analysis revealed gene networks composed of critical signaling pathways that are likely targeted by dexamethasone in podocytes.

  13. Genome-wide analysis of homeobox genes from Mesobuthus martensii reveals Hox gene duplication in scorpions.

    PubMed

    Di, Zhiyong; Yu, Yao; Wu, Yingliang; Hao, Pei; He, Yawen; Zhao, Huabin; Li, Yixue; Zhao, Guoping; Li, Xuan; Li, Wenxin; Cao, Zhijian

    2015-06-01

    Homeobox genes belong to a large gene group, which encodes the famous DNA-binding homeodomain that plays a key role in development and cellular differentiation during embryogenesis in animals. Here, one hundred forty-nine homeobox genes were identified from the Asian scorpion, Mesobuthus martensii (Chelicerata: Arachnida: Scorpiones: Buthidae) based on our newly assembled genome sequence with approximately 248 × coverage. The identified homeobox genes were categorized into eight classes including 82 families: 67 ANTP class genes, 33 PRD genes, 11 LIM genes, five POU genes, six SINE genes, 14 TALE genes, five CUT genes, two ZF genes and six unclassified genes. Transcriptome data confirmed that more than half of the genes were expressed in adults. The homeobox gene diversity of the eight classes is similar to the previously analyzed Mandibulata arthropods. Interestingly, it is hypothesized that the scorpion M. martensii may have two Hox clusters. The first complete genome-wide analysis of homeobox genes in Chelicerata not only reveals the repertoire of scorpion, arachnid and chelicerate homeobox genes, but also shows some insights into the evolution of arthropod homeobox genes.

  14. Genetic analysis of paramyxovirus isolates from pacific salmon reveals two independently co-circulating lineages

    USGS Publications Warehouse

    Batts, W.N.; Falk, K.; Winton, J.R.

    2008-01-01

    Viruses with the morphological and biochemical characteristics of the family Paramyxoviridae (paramyxoviruses) have been isolated from adult salmon returning to rivers along the Pacific coast of North America since 1982. These Pacific salmon paramyxoviruses (PSPV), which have mainly been isolated from Chinook salmon Oncorhynchus tshawytscha, grow slowly in established fish cell lines and have not been associated with disease. Genetic analysis of a 505-base-pair region of the polymerase gene from 47 PsPV isolates produced 17 nucleotide sequence types that could be grouped into two major sublineages, designated A and B. The two independently co-circulating sublineages differed by 12.1-13.9% at the nucleotide level but by only 1.2% at the amino acid level. Isolates of PSPV from adult Pacific salmon returning to rivers from Alaska to California over a 25-year period showed little evidence of geographic or temporal grouping. Phylogenetic analyses revealed that these paramyxoviruses of Pacific salmon were most closely related to the Atlantic salmon paramyxovirus (ASPV) from Norway, having a maximum nucleotide diversity of 26.1 % and an amino acid diversity of 19.0%. When compared with homologous sequences of other paramyxoviruses, PSPV and ASPV were sufficiently distinct to suggest that they are not clearly members of any of the established genera in the family Paramyxoviridae. in the course of this study, a polymerase chain reaction assay was developed that can be used for confirmatory identification of PSPV. ?? Copyright by the American Fisheries Society 2008.

  15. Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano

    PubMed Central

    Banskar, Sunil; Bhute, Shrikant S.; Suryavanshi, Mangesh V.; Punekar, Sachin; Shouche, Yogesh S.

    2016-01-01

    Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals. PMID:27845426

  16. Revealing spatio-spectral electroencephalographic dynamics of musical mode and tempo perception by independent component analysis

    PubMed Central

    2014-01-01

    Background Music conveys emotion by manipulating musical structures, particularly musical mode- and tempo-impact. The neural correlates of musical mode and tempo perception revealed by electroencephalography (EEG) have not been adequately addressed in the literature. Method This study used independent component analysis (ICA) to systematically assess spatio-spectral EEG dynamics associated with the changes of musical mode and tempo. Results Empirical results showed that music with major mode augmented delta-band activity over the right sensorimotor cortex, suppressed theta activity over the superior parietal cortex, and moderately suppressed beta activity over the medial frontal cortex, compared to minor-mode music, whereas fast-tempo music engaged significant alpha suppression over the right sensorimotor cortex. Conclusion The resultant EEG brain sources were comparable with previous studies obtained by other neuroimaging modalities, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In conjunction with advanced dry and mobile EEG technology, the EEG results might facilitate the translation from laboratory-oriented research to real-life applications for music therapy, training and entertainment in naturalistic environments. PMID:24581119

  17. iTRAQ-based quantitative proteomic analysis of Thermobifida fusca reveals metabolic pathways of cellulose utilization.

    PubMed

    Adav, Sunil S; Ng, Chee Sheng; Sze, Siu Kwan

    2011-09-06

    Thermobifida fusca is an aerobic, thermophilic, cellulose degrading bacterium identified in heated organic materials. This study applied iTRAQ quantitative proteomic analysis to the cellular and membrane proteomes of T. fusca grown in presence and absence of cellulose to elucidate the cellular processes induced by cellulose nutrient. Using an iTRAQ-based quantitative proteomic approach, 783 cytosolic and 181 membrane proteins expressed during cellulose hydrolysis were quantified with ≤1% false discovery rate. The comparative iTRAQ quantification revealed considerable induction in the expression levels and up-regulation of specific proteins in cellulosic medium than non-cellulosic medium. The regulated proteins in cellulosic medium were grouped under central carbohydrate metabolism such as glycolysis/gluconeogenesis, pentose phosphate pathways, citric acid cycle, starch, sugars, pyruvate, propanoate and butanoate metabolism; energy metabolism that includes oxidative phosphorylation, nitrogen, methane and sulfur metabolism; fatty acid metabolism, amino acid metabolic pathways, purine and pyrimidine metabolism, and main cellular genetic information processing functions like replication, transcription, translation, and cell wall synthesis; and environmental information processing (membrane transport and signal transduction). The results demonstrated cellulose induced several metabolic pathways during cellulose utilization.

  18. Rapid Holocene coastal change revealed by high-resolution micropaleontological analysis, Pamlico Sound, North Carolina, USA

    NASA Astrophysics Data System (ADS)

    Grand Pre, Candace; Culver, Stephen J.; Mallinson, David J.; Farrell, Kathleen M.; Corbett, D. Reide; Horton, Benjamin P.; Hillier, Caroline; Riggs, Stanley R.; Snyder, Scott W.; Buzas, Martin A.

    2011-11-01

    Foraminiferal analyses of 404 contiguous samples, supported by diatom, lithologic, geochronologic and seismic data, reveal both rapid and gradual Holocene paleoenvironmental changes in an 8.21-m vibracore taken from southern Pamlico Sound, North Carolina. Data record initial flooding of a latest Pleistocene river drainage and the formation of an estuary 9000 yr ago. Estuarine conditions were punctuated by two intervals of marine influence from approximately 4100 to 3700 and 1150 to 500 cal yr BP. Foraminiferal assemblages in the muddy sand facies that accumulated during these intervals contain many well-preserved benthic foraminiferal species, which occur today in open marine settings as deep as the mid shelf, and significant numbers of well-preserved planktonic foraminifera, some typical of Gulf Stream waters. We postulate that these marine-influenced units resulted from temporary destruction of the southern Outer Banks barrier islands by hurricanes. The second increase in marine influence is coeval with increased rate of sea-level rise and a peak in Atlantic tropical cyclone activity during the Medieval Climate Anomaly. This high-resolution analysis demonstrates the range of environmental variability and the rapidity of coastal change that can result from the interplay of changing climate, sea level and geomorphology in an estuarine setting.

  19. AKAP signaling in reinstated cocaine seeking revealed by iTRAQ proteomic analysis.

    PubMed

    Reissner, Kathryn J; Uys, Joachim D; Schwacke, John H; Comte-Walters, Susanna; Rutherford-Bethard, Jennifer L; Dunn, Thomas E; Blumer, Joe B; Schey, Kevin L; Kalivas, Peter W

    2011-04-13

    To identify candidate proteins in the nucleus accumbens (NAc) as potential pharmacotherapeutic targets for treating cocaine addition, an 8-plex iTRAQ (isobaric tag for relative and absolute quantitation) proteomic screen was performed using NAc tissue obtained from rats trained to self-administer cocaine followed by extinction training. Compared with yoked-saline controls, 42 proteins in a postsynaptic density (PSD)-enriched subfraction of the NAc from cocaine-trained animals were identified as significantly changed. Among proteins of interest whose levels were identified as increased was AKAP79/150, the rat ortholog of human AKAP5, a PSD scaffolding protein that localizes signaling molecules to the synapse. Functional downregulation of AKAP79/150 by microinjecting a cell-permeable synthetic AKAP (A-kinase anchor protein) peptide into the NAc to disrupt AKAP-dependent signaling revealed that inhibition of AKAP signaling impaired the reinstatement of cocaine seeking. Reinstatement of cocaine seeking is thought to require upregulated surface expression of AMPA glutamate receptors, and the inhibitory AKAP peptide reduced the PSD content of protein kinase A (PKA) as well as surface expression of GluR1 in NAc. However, reduced surface expression was not associated with changes in PKA phosphorylation of GluR1. This series of experiments demonstrates that proteomic analysis provides a useful tool for identifying proteins that can regulate cocaine relapse and that AKAP proteins may contribute to relapse vulnerability by promoting increased surface expression of AMPA receptors in the NAc.

  20. A Simple Geotracer Compositional Correlation Analysis Reveals Oil Charge and Migration Pathways

    NASA Astrophysics Data System (ADS)

    Yang, Yunlai; Arouri, Khaled

    2016-03-01

    A novel approach, based on geotracer compositional correlation analysis is reported, which reveals the oil charge sequence and migration pathways for five oil fields in Saudi Arabia. The geotracers utilised are carbazoles, a family of neutral pyrrolic nitrogen compounds known to occur naturally in crude oils. The approach is based on the concept that closely related fields, with respect to filling sequence, will show a higher carbazole compositional correlation, than those fields that are less related. That is, carbazole compositional correlation coefficients can quantify the charge and filling relationships among different fields. Consequently, oil migration pathways can be defined based on the established filling relationships. The compositional correlation coefficients of isomers of C1 and C2 carbazoles, and benzo[a]carbazole for all different combination pairs of the five fields were found to vary extremely widely (0.28 to 0.94). A wide range of compositional correlation coefficients allows adequate differentiation of separate filling relationships. Based on the established filling relationships, three distinct migration pathways were inferred, with each apparently being charged from a different part of a common source kitchen. The recognition of these charge and migration pathways will greatly aid the search for new accumulations.

  1. A Quorum-Sensing Factor in Vegetative Dictyostelium Discoideum Cells Revealed by Quantitative Migration Analysis

    PubMed Central

    Golé, Laurent; Rivière, Charlotte; Hayakawa, Yoshinori; Rieu, Jean-Paul

    2011-01-01

    Background Many cells communicate through the production of diffusible signaling molecules that accumulate and once a critical concentration has been reached, can activate or repress a number of target genes in a process termed quorum sensing (QS). In the social amoeba Dictyostelium discoideum, QS plays an important role during development. However little is known about its effect on cell migration especially in the growth phase. Methods and Findings To investigate the role of cell density on cell migration in the growth phase, we use multisite timelapse microscopy and automated cell tracking. This analysis reveals a high heterogeneity within a given cell population, and the necessity to use large data sets to draw reliable conclusions on cell motion. In average, motion is persistent for short periods of time (), but normal diffusive behavior is recovered over longer time periods. The persistence times are positively correlated with the migrated distances. Interestingly, the migrated distance decreases as well with cell density. The adaptation of cell migration to cell density highlights the role of a secreted quorum sensing factor (QSF) on cell migration. Using a simple model describing the balance between the rate of QSF generation and the rate of QSF dilution, we were able to gather all experimental results into a single master curve, showing a sharp cell transition between high and low motile behaviors with increasing QSF. Conclusion This study unambiguously demonstrates the central role played by QSF on amoeboid motion in the growth phase. PMID:22073217

  2. Biometric variability of goat populations revealed by means of principal component analysis

    PubMed Central

    Pires, Luanna Chácara; Machado, Théa M. Medeiros; Araújo, Adriana Mello; Olson, Timothy A.; da Silva, João Batista Lopes; Torres, Robledo Almeida; Costa, Márcio da Silva

    2012-01-01

    The aim was to analyze variation in 12 Brazilian and Moroccan goat populations, and, through principal component analysis (PCA), check the importance of body measures and their indices as a means of distinguishing among individuals and populations. The biometric measurements were wither height (WH), brisket height (BH) and ear length (EL). Thorax depth (WH-BH) and the three indices, TD/WH, EL/TD and EL/WH, were also calculated. Of the seven components extracted, the first three principal components were sufficient to explain 99.5% of the total variance of the data. Graphical dispersion by genetic groups revealed that European dairy breeds clustered together. The Moroccan breeds were separated into two groups, one comprising the Drâa and the other the Zagora and Rhâali breeds. Whereas, on the one side, the Anglo-Nubian and undefined breeds were the closest to one another the goats of the Azul were observed to have the highest variation of all the breeds. The Anglo-Nubian and Boer breeds were similar to each other. The Nambi-type goats remained distinct from all the other populations. In general, the use of graphical representation of PCA values allowed to distinguish genetic groups. PMID:23271938

  3. Global analysis of transcriptionally engaged yeast RNA polymerase III reveals extended tRNA transcripts

    PubMed Central

    Turowski, Tomasz W.; Leśniewska, Ewa; Delan-Forino, Clementine; Sayou, Camille; Boguta, Magdalena; Tollervey, David

    2016-01-01

    RNA polymerase III (RNAPIII) synthesizes a range of highly abundant small stable RNAs, principally pre-tRNAs. Here we report the genome-wide analysis of nascent transcripts attached to RNAPIII under permissive and restrictive growth conditions. This revealed strikingly uneven polymerase distributions across transcription units, generally with a predominant 5′ peak. This peak was higher for more heavily transcribed genes, suggesting that initiation site clearance is rate-limiting during RNAPIII transcription. Down-regulation of RNAPIII transcription under stress conditions was found to be uneven; a subset of tRNA genes showed low response to nutrient shift or loss of the major transcription regulator Maf1, suggesting potential “housekeeping” roles. Many tRNA genes were found to generate long, 3′-extended forms due to read-through of the canonical poly(U) terminators. The degree of read-through was anti-correlated with the density of U-residues in the nascent tRNA, and multiple, functional terminators can be located far downstream. The steady-state levels of 3′-extended pre-tRNA transcripts are low, apparently due to targeting by the nuclear surveillance machinery, especially the RNA binding protein Nab2, cofactors for the nuclear exosome, and the 5′-exonuclease Rat1. PMID:27206856

  4. RNA-Seq Analysis Reveals Candidate Targets for Curcumin against Tetranychus cinnabarinus

    PubMed Central

    Wu, Dousheng; Zhang, Yongqiang; Zhou, Hong; Lai, Ting

    2016-01-01

    Tetranychus cinnabarinus is an important agricultural pest with a broad host range. We previously identified curcumin as a promising acaricidal compound against T. cinnabarinus. However, the acaricidal mechanism of curcumin remains unknown. In this study, RNA-seq was employed to analyze the transcriptome changes in T. cinnabarinus treated with curcumin or the solvent. A total of 105,706,297 clean sequence reads were generated by sequencing, with more than 90% of the reads successfully mapped to the reference sequence. The RNA-seq identified 111 and 96 differentially expressed genes between curcumin- and solvent-treated mites at 24 and 48 h after treatment, respectively. GO enrichment analysis of differentially expressed genes showed that the cellular process was the dominant group at both time points. Finally, we screened 23 differentially expressed genes that were functionally identical or similar to the targets of common insecticide/acaricides or genes that were associated with mite detoxification and metabolism. Calmodulin, phospholipase A2, and phospholipase C were activated upon curcumin treatment suggesting that the calcium channel related genes might play important roles in mite's response to curcumin. Overall our results revealed the global transcriptional changes in T. cinnabarinus after curcumin treatment to enable further identification of the targets of curcumin in mites. PMID:27672652

  5. Integrated Analysis of Alzheimer's Disease and Schizophrenia Dataset Revealed Different Expression Pattern in Learning and Memory.

    PubMed

    Li, Wen-Xing; Dai, Shao-Xing; Liu, Jia-Qian; Wang, Qian; Li, Gong-Hua; Huang, Jing-Fei

    2016-01-01

    Alzheimer's disease (AD) and schizophrenia (SZ) are both accompanied by impaired learning and memory functions. This study aims to explore the expression profiles of learning or memory genes between AD and SZ. We downloaded 10 AD and 10 SZ datasets from GEO-NCBI for integrated analysis. These datasets were processed using RMA algorithm and a global renormalization for all studies. Then Empirical Bayes algorithm was used to find the differentially expressed genes between patients and controls. The results showed that most of the differentially expressed genes were related to AD whereas the gene expression profile was little affected in the SZ. Furthermore, in the aspects of the number of differentially expressed genes, the fold change and the brain region, there was a great difference in the expression of learning or memory related genes between AD and SZ. In AD, the CALB1, GABRA5, and TAC1 were significantly downregulated in whole brain, frontal lobe, temporal lobe, and hippocampus. However, in SZ, only two genes CRHBP and CX3CR1 were downregulated in hippocampus, and other brain regions were not affected. The effect of these genes on learning or memory impairment has been widely studied. It was suggested that these genes may play a crucial role in AD or SZ pathogenesis. The different gene expression patterns between AD and SZ on learning and memory functions in different brain regions revealed in our study may help to understand the different mechanism between two diseases.

  6. Large-Scale Phosphoproteomics Analysis of Whole Saliva Reveals a Distinct Phosphorylation Pattern

    PubMed Central

    Stone, Matthew D.; Chen, Xiaobing; McGowan, Thomas; Bandhakavi, Sricharan; Cheng, Bin; Rhodus, Nelson L.; Griffin, Timothy J.

    2011-01-01

    In-depth knowledge of bodily fluid phosphoproteomes, such as whole saliva, is limited. To better understand the whole saliva phosphoproteome, we generated a large-scale catalog of phosphorylated proteins. To circumvent the wide dynamic range of phosphoprotein abundance in whole saliva, we combined dynamic range compression using hexapeptide beads, strong cation exchange HPLC peptide fractionation, and immobilized metal affinity chromatography prior to mass spectrometry. In total, 217 unique phosphopeptides sites were identified representing 85 distinct phosphoproteins at 2.3% global FDR. From these peptides, 129 distinct phosphorylation sites were identified of which 57 were previously known, but only 11 of which had been previously identified in whole saliva. Cellular localization analysis revealed salivary phosphoproteins had a distribution similar to all known salivary proteins, but with less relative representation in “extracellular” and “plasma membrane” categories compared to salivary glycoproteins. Sequence alignment showed that phosphorylation occurred at acidic-directed kinase, proline-directed, and basophilic motifs. This differs from plasma phosphoproteins, which predominantly occur at Golgi casein kinase recognized sequences. Collectively, these results suggest diverse functions for salivary phosphoproteins and multiple kinases involved in their processing and secretion. In all, this study should lay groundwork for future elucidation of the functions of salivary protein phosphorylation. PMID:21299198

  7. Orbital forcing on West African monsoon system revealed by KZai 02 pollen record spectral analysis

    NASA Astrophysics Data System (ADS)

    Dalibard, Mathieu; Popescu, Speranta-Maria; Pittet, Bernard; Fernandez, Vincent; Marsset, Tania; Droz, Laurence; Suc, Jean-Pierre

    2013-04-01

    The present-day intertropical climate is forced by yearly fluctuations of insolation reorganizing pressure cells. They control, via the wind system, the variations of the precipitation front known as the InterTropical Convergence Zone (ITCZ). Its latitudinal oscillation drives a strong seasonality of rainfalls over Africa. However, connections between African climate during Pleistocene and orbital forcing are blurred by high-latitudes and local direct influence of insolation and need further investigations. The study of KZai 02 core pollen content provides a high-resolution record of changes in West African plant ecosystems during the last 160 kyrs. Spectral analyses were performed on pollen signals to identify periodicity in vegetation dynamics related to environmental fluctuations. The large range of frequencies detected testifies for the sensibility of African biotopes to past climate fluctuations. Milankovitch parameters, especially precession, are identified within variations of the ecological groups of KZai 02 pollen record and interpreted in terms of West African monsoon system variability. Asynchrony in the different plant ecosystem fluctuations suggests the out of step influence of several climatic parameters (precipitation, CO2, temperature) involving local insolation and high-latitude influence. Spectral analysis also reveals sub-Milankovitch periods related to (1) Heinrich and Dansgaard/Oeschger glacial pulsation events and (2) East Asian monsoon oscillations controlled by ice sheet pulses testifying for the strong relationship between low- and high-latitude climate changes.

  8. Microbiome analysis reveals the abundance of bacterial pathogens in Rousettus leschenaultii guano.

    PubMed

    Banskar, Sunil; Bhute, Shrikant S; Suryavanshi, Mangesh V; Punekar, Sachin; Shouche, Yogesh S

    2016-11-15

    Bats are crucial for proper functioning of an ecosystem. They provide various important services to ecosystem and environment. While, bats are well-known carrier of pathogenic viruses, their possible role as a potential carrier of pathogenic bacteria is under-explored. Here, using culture-based approach, employing multiple bacteriological media, over thousand bacteria were cultivated and identified from Rousettus leschenaultii (a frugivorous bat species), the majority of which were from the family Enterobacteriaceae and putative pathogens. Next, pathogenic potential of most frequently cultivated component of microbiome i.e. Escherichia coli was assessed to identify its known pathotypes which revealed the presence of virulent factors in many cultivated E. coli isolates. Applying in-depth bacterial community analysis using high-throughput 16 S rRNA gene sequencing, a high inter-individual variation was observed among the studied guano samples. Interestingly, a higher diversity of bacterial communities was observed in decaying guano representative. The search against human pathogenic bacteria database at 97% identity, a small proportion of sequences were found associated to well-known human pathogens. The present study thus indicates that this bat species may carry potential bacterial pathogens and advice to study the effect of these pathogens on bats itself and the probable mode of transmission to humans and other animals.

  9. Population-based 3D genome structure analysis reveals driving forces in spatial genome organization

    PubMed Central

    Li, Wenyuan; Kalhor, Reza; Dai, Chao; Hao, Shengli; Gong, Ke; Zhou, Yonggang; Li, Haochen; Zhou, Xianghong Jasmine; Le Gros, Mark A.; Larabell, Carolyn A.; Chen, Lin; Alber, Frank

    2016-01-01

    Conformation capture technologies (e.g., Hi-C) chart physical interactions between chromatin regions on a genome-wide scale. However, the structural variability of the genome between cells poses a great challenge to interpreting ensemble-averaged Hi-C data, particularly for long-range and interchromosomal interactions. Here, we present a probabilistic approach for deconvoluting Hi-C data into a model population of distinct diploid 3D genome structures, which facilitates the detection of chromatin interactions likely to co-occur in individual cells. Our approach incorporates the stochastic nature of chromosome conformations and allows a detailed analysis of alternative chromatin structure states. For example, we predict and experimentally confirm the presence of large centromere clusters with distinct chromosome compositions varying between individual cells. The stability of these clusters varies greatly with their chromosome identities. We show that these chromosome-specific clusters can play a key role in the overall chromosome positioning in the nucleus and stabilizing specific chromatin interactions. By explicitly considering genome structural variability, our population-based method provides an important tool for revealing novel insights into the key factors shaping the spatial genome organization. PMID:26951677

  10. Highly distinct chromosomal structures in cowpea (Vigna unguiculata), as revealed by molecular cytogenetic analysis.

    PubMed

    Iwata-Otsubo, Aiko; Lin, Jer-Young; Gill, Navdeep; Jackson, Scott A

    2016-05-01

    Cowpea (Vigna unguiculata (L.) Walp) is an important legume, particularly in developing countries. However, little is known about its genome or chromosome structure. We used molecular cytogenetics to characterize the structure of pachytene chromosomes to advance our knowledge of chromosome and genome organization of cowpea. Our data showed that cowpea has highly distinct chromosomal structures that are cytologically visible as brightly DAPI-stained heterochromatic regions. Analysis of the repetitive fraction of the cowpea genome present at centromeric and pericentromeric regions confirmed that two retrotransposons are major components of pericentromeric regions and that a 455-bp tandem repeat is found at seven out of 11 centromere pairs in cowpea. These repeats likely evolved after the divergence of cowpea from common bean and form chromosomal structure unique to cowpea. The integration of cowpea genetic and physical chromosome maps reveals potential regions of suppressed recombination due to condensed heterochromatin and a lack of pairing in a few chromosomal termini. This study provides fundamental knowledge on cowpea chromosome structure and molecular cytogenetics tools for further chromosome studies.

  11. Comparative Analysis of Membrane Vesicles from Three Piscirickettsia salmonis Isolates Reveals Differences in Vesicle Characteristics

    PubMed Central

    Tandberg, Julia I.; Lagos, Leidy X.; Langlete, Petter; Berger, Eva; Rishovd, Anne-Lise; Roos, Norbert; Varkey, Deepa; Paulsen, Ian T.; Winther-Larsen, Hanne C.

    2016-01-01

    Membrane vesicles (MVs) are spherical particles naturally released from the membrane of Gram-negative bacteria. Bacterial MV production is associated with a range of phenotypes including biofilm formation, horizontal gene transfer, toxin delivery, modulation of host immune responses and virulence. This study reports comparative profiling of MVs from bacterial strains isolated from three widely disperse geographical areas. Mass spectrometry identified 119, 159 and 142 proteins in MVs from three different strains of Piscirickettsia salmonis isolated from salmonids in Chile (LF-89), Norway (NVI 5692) and Canada (NVI 5892), respectively. MV comparison revealed several strain-specific differences related to higher virulence capability for LF-89 MVs, both in vivo and in vitro, and stronger similarities between the NVI 5692 and NVI 5892 MV proteome. The MVs were similar in size and appearance as analyzed by electron microscopy and dynamic light scattering. The MVs from all three strains were internalized by both commercial and primary immune cell cultures, which suggest a potential role of the MVs in the bacterium’s utilization of leukocytes. When MVs were injected into an adult zebrafish infection model, an upregulation of several pro-inflammatory genes were observed in spleen and kidney, indicating a modulating effect on the immune system. The present study is the first comparative analysis of P. salmonis derived MVs, highlighting strain-specific vesicle characteristics. The results further illustrate that the MV proteome from one bacterial strain is not representative of all bacterial strains within one species. PMID:27764198

  12. Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer

    PubMed Central

    Arthur, Janelle C.; Gharaibeh, Raad Z.; Mühlbauer, Marcus; Perez-Chanona, Ernesto; Uronis, Joshua M.; McCafferty, Jonathan; Fodor, Anthony A.; Jobin, Christian

    2014-01-01

    Enterobacteria, especially Escherichia coli, are abundant in patients with inflammatory bowel disease or colorectal cancer (CRC). However, it is unclear whether cancer is promoted by inflammation-induced expansion of E. coli and/or changes in expression of specific microbial genes. Here we use longitudinal (2, 12 and 20 weeks) 16S rRNA sequencing of luminal microbiota from ex-germ free mice to show that inflamed Il10−/− mice maintain a higher abundance of Enterobacteriaceae than healthy wild-type mice. Experiments with mono-colonized Il10−/− mice reveal that host inflammation is necessary for E. coli cancer-promoting activity. RNA-sequence analysis indicates significant changes in E. coli gene catalogue in Il10−/− mice, with changes mostly driven by adaptation to the intestinal environment. Expression of specific genes present in the tumor-promoting E. coli pks island are modulated by inflammation/CRC development. Thus, progression of inflammation in Il10−/− mice supports Enterobacteriaceae and alters a small subset of microbial genes important for tumor development. PMID:25182170

  13. Retrospective stable isotope analysis reveals ecosystem responses to river regulation over the last century.

    PubMed

    Turner, Thomas F; Krabbenhoft, Trevor I; Collyer, Michael L; Krabbenhoft, Corey A; Edwards, Melanie S; Sharp, Zachary D

    2015-12-01

    Disruption of natural flow regimes, nutrient pollution, and other consequences of human population growth and development have impacted most major rivers of the world. Alarming losses of aquatic biodiversity coincide with human-caused river alteration, but effects of biotic homogenization on aquatic ecosystem processes are not as well documented. This is because unaltered systems for comparison are scarce, and some ecosystem-wide effects may take decades to manifest. We evaluated aquatic ecosystem responses to extensive river- floodplain engineering and nutrient addition in the Rio Grande of southwestern North America as revealed by changes in trophic structure of, and resource availability to, the fish community. Stable Isotope Analysis (SIA) was conducted on museum-preserved fishes collected over a 70-year period of intensive river management and exponential human population growth. Trophic complexity and resource heterogeneity for fish consumers (measured as "isotopic niche breadth") decreased following sediment deprivation and channelization, and these effects persist into the present. Increased nutrient inputs led to δ15N enrichment in the entire fish community at all affected sites, and a shift to autochthonous sources of carbon at the most proximal site downstream of wastewater release, probably via bottom-up transfer. Overall, retrospective SIA of apex consumers suggests radical change and functional impairment of a floodplain river ecosystem already marked by significant biodiversity loss.

  14. Multi-locus phylogenetic analysis reveals the pattern and tempo of bony fish evolution

    PubMed Central

    Broughton, Richard E.; Betancur-R., Ricardo; Li, Chenhong; Arratia, Gloria; Ortí, Guillermo

    2013-01-01

    Over half of all vertebrates are “fishes”, which exhibit enormous diversity in morphology, physiology, behavior, reproductive biology, and ecology. Investigation of fundamental areas of vertebrate biology depend critically on a robust phylogeny of fishes, yet evolutionary relationships among the major actinopterygian and sarcopterygian lineages have not been conclusively resolved. Although a consensus phylogeny of teleosts has been emerging recently, it has been based on analyses of various subsets of actinopterygian taxa, but not on a full sample of all bony fishes. Here we conducted a comprehensive phylogenetic study on a broad taxonomic sample of 61 actinopterygian and sarcopterygian lineages (with a chondrichthyan outgroup) using a molecular data set of 21 independent loci. These data yielded a resolved phylogenetic hypothesis for extant Osteichthyes, including 1) reciprocally monophyletic Sarcopterygii and Actinopterygii, as currently understood, with polypteriforms as the first diverging lineage within Actinopterygii; 2) a monophyletic group containing gars and bowfin (= Holostei) as sister group to teleosts; and 3) the earliest diverging lineage among teleosts being Elopomorpha, rather than Osteoglossomorpha. Relaxed-clock dating analysis employing a set of 24 newly applied fossil calibrations reveals divergence times that are more consistent with paleontological estimates than previous studies. Establishing a new phylogenetic pattern with accurate divergence dates for bony fishes illustrates several areas where the fossil record is incomplete and provides critical new insights on diversification of this important vertebrate group. PMID:23788273

  15. Rapid Holocene coastal change revealed by high-resolution micropaleontological analysis, Pamlico Sound, North Carolina, USA

    USGS Publications Warehouse

    Grand, Pre C.; Culver, S.J.; Mallinson, D.J.; Farrell, K.M.; Corbett, D.R.; Horton, B.P.; Hillier, C.; Riggs, S.R.; Snyder, S.W.; Buzas, M.A.

    2011-01-01

    Foraminiferal analyses of 404 contiguous samples, supported by diatom, lithologic, geochronologic and seismic data, reveal both rapid and gradual Holocene paleoenvironmental changes in an 8.21-m vibracore taken from southern Pamlico Sound, North Carolina. Data record initial flooding of a latest Pleistocene river drainage and the formation of an estuary 9000. yr ago. Estuarine conditions were punctuated by two intervals of marine influence from approximately 4100 to 3700 and 1150 to 500. cal. yr BP. Foraminiferal assemblages in the muddy sand facies that accumulated during these intervals contain many well-preserved benthic foraminiferal species, which occur today in open marine settings as deep as the mid shelf, and significant numbers of well-preserved planktonic foraminifera, some typical of Gulf Stream waters. We postulate that these marine-influenced units resulted from temporary destruction of the southern Outer Banks barrier islands by hurricanes. The second increase in marine influence is coeval with increased rate of sea-level rise and a peak in Atlantic tropical cyclone activity during the Medieval Climate Anomaly. This high-resolution analysis demonstrates the range of environmental variability and the rapidity of coastal change that can result from the interplay of changing climate, sea level and geomorphology in an estuarine setting. ?? 2011 University of Washington.

  16. Metatranscriptome analysis reveals host-microbiome interactions in traps of carnivorous Genlisea species

    PubMed Central

    Cao, Hieu X.; Schmutzer, Thomas; Scholz, Uwe; Pecinka, Ales; Schubert, Ingo; Vu, Giang T. H.

    2015-01-01

    In the carnivorous plant genus Genlisea a unique lobster pot trapping mechanism supplements nutrition in nutrient-poor habitats. A wide spectrum of microbes frequently occurs in Genlisea's leaf-derived traps without clear relevance for Genlisea carnivory. We sequenced the metatranscriptomes of subterrestrial traps vs. the aerial chlorophyll-containing leaves of G. nigrocaulis and of G. hispidula. Ribosomal RNA assignment revealed soil-borne microbial diversity in Genlisea traps, with 92 genera of 19 phyla present in more than one sample. Microbes from 16 of these phyla including proteobacteria, green algae, amoebozoa, fungi, ciliates and metazoans, contributed additionally short-lived mRNA to the metatranscriptome. Furthermore, transcripts of 438 members of hydrolases (e.g., proteases, phosphatases, lipases), mainly resembling those of metazoans, ciliates and green algae, were found. Compared to aerial leaves, Genlisea traps displayed a transcriptional up-regulation of endogenous NADH oxidases generating reactive oxygen species as well as of acid phosphatases for prey digestion. A leaf-vs.-trap transcriptome comparison reflects that carnivory provides inorganic P- and different forms of N-compounds (ammonium, nitrate, amino acid, oligopeptides) and implies the need to protect trap cells against oxidative stress. The analysis elucidates a complex food web inside the Genlisea traps, and suggests ecological relationships between this plant genus and its entrapped microbiome. PMID:26236284

  17. Meta-analysis of retrograde signaling in Arabidopsis thaliana reveals a core module of genes embedded in complex cellular signaling networks.

    PubMed

    Gläßer, Christine; Haberer, Georg; Finkemeier, Iris; Pfannschmidt, Thomas; Kleine, Tatjana; Leister, Dario; Dietz, Karl-Josef; Häusler, Rainer Erich; Grimm, Bernhard; Mayer, Klaus Franz Xaver

    2014-07-01

    Plastid-to-nucleus signaling is essential for the coordination and adjustment of cellular metabolism in response to environmental and developmental cues of plant cells. A variety of operational retrograde signaling pathways have been described that are thought to be triggered by reactive oxygen species, photosynthesis redox imbalance, tetrapyrrole intermediates, and other metabolic traits. Here we report a meta-analysis based on transcriptome and protein interaction data. Comparing the output of these pathways reveals the commonalities and peculiarities stimulated by six different sources impinging on operational retrograde signaling. Our study provides novel insights into the interplay of these pathways, supporting the existence of an as-yet unknown core response module of genes being regulated under all conditions tested. Our analysis further highlights affiliated regulatory cis-elements and classifies abscisic acid and auxin-based signaling as secondary components involved in the response cascades following a plastidial signal. Our study provides a global analysis of structure and interfaces of different pathways involved in plastid-to-nucleus signaling and a new view on this complex cellular communication network.

  18. The Immersive Virtual Reality Experience: A Typology of Users Revealed Through Multiple Correspondence Analysis Combined with Cluster Analysis Technique.

    PubMed

    Rosa, Pedro J; Morais, Diogo; Gamito, Pedro; Oliveira, Jorge; Saraiva, Tomaz

    2016-03-01

    Immersive virtual reality is thought to be advantageous by leading to higher levels of presence. However, and despite users getting actively involved in immersive three-dimensional virtual environments that incorporate sound and motion, there are individual factors, such as age, video game knowledge, and the predisposition to immersion, that may be associated with the quality of virtual reality experience. Moreover, one particular concern for users engaged in immersive virtual reality environments (VREs) is the possibility of side effects, such as cybersickness. The literature suggests that at least 60% of virtual reality users report having felt symptoms of cybersickness, which reduces the quality of the virtual reality experience. The aim of this study was thus to profile the right user to be involved in a VRE through head-mounted display. To examine which user characteristics are associated with the most effective virtual reality experience (lower cybersickness), a multiple correspondence analysis combined with cluster analysis technique was performed. Results revealed three distinct profiles, showing that the PC gamer profile is more associated with higher levels of virtual reality effectiveness, that is, higher predisposition to be immersed and reduced cybersickness symptoms in the VRE than console gamer and nongamer. These findings can be a useful orientation in clinical practice and future research as they help identify which users are more predisposed to benefit from immersive VREs.

  19. Proteomic and bioinformatic analysis of epithelial tight junction reveals an unexpected cluster of synaptic molecules

    PubMed Central

    Tang, Vivian W

    2006-01-01

    Background Zonula occludens, also known as the tight junction, is a specialized cell-cell interaction characterized by membrane "kisses" between epithelial cells. A cytoplasmic plaque of ~100 nm corresponding to a meshwork of densely packed proteins underlies the tight junction membrane domain. Due to its enormous size and difficulties in obtaining a biochemically pure fraction, the molecular composition of the tight junction remains largely unknown. Results A novel biochemical purification protocol has been developed to isolate tight junction protein complexes from cultured human epithelial cells. After identification of proteins by mass spectroscopy and fingerprint analysis, candidate proteins are scored and assessed individually. A simple algorithm has been devised to incorporate transmembrane domains and protein modification sites for scoring membrane proteins. Using this new scoring system, a total of 912 proteins have been identified. These 912 hits are analyzed using a bioinformatics approach to bin the hits in 4 categories: configuration, molecular function, cellular function, and specialized process. Prominent clusters of proteins related to the cytoskeleton, cell adhesion, and vesicular traffic have been identified. Weaker clusters of proteins associated with cell growth, cell migration, translation, and transcription are also found. However, the strongest clusters belong to synaptic proteins and signaling molecules. Localization studies of key components of synaptic transmission have confirmed the presence of both presynaptic and postsynaptic proteins at the tight junction domain. To correlate proteomics data with structure, the tight junction has been examined using electron microscopy. This has revealed many novel structures including end-on cytoskeletal attachments, vesicles fusing/budding at the tight junction membrane domain, secreted substances encased between the tight junction kisses, endocytosis of tight junction double membranes, satellite

  20. Genomic Convergence Analysis of Schizophrenia: mRNA Sequencing Reveals Altered Synaptic Vesicular Transport in Post-Mortem Cerebellum

    PubMed Central

    Mudge, Joann; Miller, Neil A.; Khrebtukova, Irina; Lindquist, Ingrid E.; May, Gregory D.; Huntley, Jim J.; Luo, Shujun; Zhang, Lu; van Velkinburgh, Jennifer C.; Farmer, Andrew D.; Lewis, Sharon; Beavis, William D.; Schilkey, Faye D.; Virk, Selene M.; Black, C. Forrest; Myers, M. Kathy; Mader, Lar C.; Langley, Ray J.; Utsey, John P.; Kim, Ryan W.; Roberts, Rosalinda C.; Khalsa, Sat Kirpal; Garcia, Meredith; Ambriz-Griffith, Victoria; Harlan, Richard; Czika, Wendy; Martin, Stanton; Wolfinger, Russell D.; Perrone-Bizzozero, Nora I.; Schroth, Gary P.; Kingsmore, Stephen F.

    2008-01-01

    Schizophrenia (SCZ) is a common, disabling mental illness with high heritability but complex, poorly understood genetic etiology. As the first phase of a genomic convergence analysis of SCZ, we generated 16.7 billion nucleotides of short read, shotgun sequences of cDNA from post-mortem cerebellar cortices of 14 patients and six, matched controls. A rigorous analysis pipeline was developed for analysis of digital gene expression studies. Sequences aligned to approximately 33,200 transcripts in each sample, with average coverage of 450 reads per gene. Following adjustments for confounding clinical, sample and experimental sources of variation, 215 genes differed significantly in expression between cases and controls. Golgi apparatus, vesicular transport, membrane association, Zinc binding and regulation of transcription were over-represented among differentially expressed genes. Twenty three genes with altered expression and involvement in presynaptic vesicular transport, Golgi function and GABAergic neurotransmission define a unifying molecular hypothesis for dysfunction in cerebellar cortex in SCZ. PMID:18985160

  1. Cost-effectiveness analysis of dialysis and kidney transplant in patients with renal impairment using disability adjusted life years in Iran

    PubMed Central

    YaghoubiFard, Safiye; Goudarzi, Reza; Etminan, Abbas; Baneshi, MohammadReza; Barouni, Mohsen; Jafari Sirizi, Mohammad

    2016-01-01

    Background: This cross-sectional study was conducted to compare the cost-effectiveness of three therapeutic methods of long-term hemodialysis, kidney transplant from a living person and kidney transplant from a cadaver utilizing Disability Adjusted Life Years (DALY) using data from the records of patients referred to Afzalipour Hospital of Kerman in 2012. Methods: This cross-sectional study utilizing Disability Adjusted Life Years (DALY) as outcome measure, used data from the records of patients referred to Afzalipour Hospital of Kerman in 2012. The decision tree model and decision tree software (Tree Age pro 11) were used for data analysis. In this research, costs and effects were studied from the patients and healthcare providers’ perspective. Results: In the patient’s perspective, the CER of dialysis was 5.04 times greater than transplant from a living person and 6.15 times higher than transplant from a cadaveric donor. In the hospital’s perspective, the average cost-effectiveness ratio of dialysis was 8.4 times greater than transplant from a living person and 14.07 times higher than transplant from a cadaver. The smaller the C-E ratio, the greater was the cost-effectiveness. In both perspectives, the order of effectiveness of treatment methods were transplant from a cadaver, transplant from a living person and dialysis. Conclusion: Considering the results obtained in this study, measures should be taken to increase the desire for organ donation from brain-dead patients, living people and patients’ relatives PMID:27493934

  2. Novel relationships among ten fish model species revealed based on a phylogenomic analysis using ESTs.

    PubMed

    Steinke, Dirk; Salzburger, Walter; Meyer, Axel

    2006-06-01

    The power of comparative phylogenomic analyses also depends on the amount of data that are included in such studies. We used expressed sequence tags (ESTs) from fish model species as a proof of principle approach in order to test the reliability of using ESTs for phylogenetic inference. As expected, the robustness increases with the amount of sequences. Although some progress has been made in the elucidation of the phylogeny of teleosts, relationships among the main lineages of the derived fish (Euteleostei) remain poorly defined and are still debated. We performed a phylogenomic analysis of a set of 42 of orthologous genes from 10 available fish model systems from seven different orders (Salmoniformes, Siluriformes, Cypriniformes, Tetraodontiformes, Cyprinodontiformes, Beloniformes, and Perciformes) of euteleostean fish to estimate divergence times and evolutionary relationships among those lineages. All 10 fish species serve as models for developmental, aquaculture, genomic, and comparative genetic studies. The phylogenetic signal and the strength of the contribution of each of the 42 orthologous genes were estimated with randomly chosen data subsets. Our study revealed a molecular phylogeny of higher-level relationships of derived teleosts, which indicates that the use of multiple genes produces robust phylogenies, a finding that is expected to apply to other phylogenetic issues among distantly related taxa. Our phylogenomic analyses confirm that the euteleostean superorders Ostariophysi and Acanthopterygii are monophyletic and the Protacanthopterygii and Ostariophysi are sister clades. In addition, and contrary to the traditional phylogenetic hypothesis, our analyses determine that killifish (Cyprinodontiformes), medaka (Beloniformes), and cichlids (Perciformes) appear to be more closely related to each other than either of them is to pufferfish (Tetraodontiformes). All 10 lineages split before or during the fragmentation of the supercontinent Pangea in the

  3. Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

    PubMed Central

    2013-01-01

    Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. Results Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. PMID:24131581

  4. Molecular Determinants of Juvenile Hormone Action as Revealed by 3D QSAR Analysis in Drosophila

    PubMed Central

    Beňo, Milan; Farkaš, Robert

    2009-01-01

    Background Postembryonic development, including metamorphosis, of many animals is under control of hormones. In Drosophila and other insects these developmental transitions are regulated by the coordinate action of two principal hormones, the steroid ecdysone and the sesquiterpenoid juvenile hormone (JH). While the mode of ecdysone action is relatively well understood, the molecular mode of JH action remains elusive. Methodology/Principal Findings To gain more insights into the molecular mechanism of JH action, we have tested the biological activity of 86 structurally diverse JH agonists in Drosophila melanogaster. The results were evaluated using 3D QSAR analyses involving CoMFA and CoMSIA procedures. Using this approach we have generated both computer-aided and species-specific pharmacophore fingerprints of JH and its agonists, which revealed that the most active compounds must possess an electronegative atom (oxygen or nitrogen) at both ends of the molecule. When either of these electronegative atoms are replaced by carbon or the distance between them is shorter than 11.5 Å or longer than 13.5 Å, their biological activity is dramatically decreased. The presence of an electron-deficient moiety in the middle of the JH agonist is also essential for high activity. Conclusions/Significance The information from 3D QSAR provides guidelines and mechanistic scope for identification of steric and electrostatic properties as well as donor and acceptor hydrogen-bonding that are important features of the ligand-binding cavity of a JH target protein. In order to refine the pharmacophore analysis and evaluate the outcomes of the CoMFA and CoMSIA study we used pseudoreceptor modeling software PrGen to generate a putative binding site surrogate that is composed of eight amino acid residues corresponding to the defined molecular interactions. PMID:19547707

  5. Star-disk interaction in classical T Tauri stars revealed using wavelet analysis

    NASA Astrophysics Data System (ADS)

    López-Santiago, J.; Crespo-Chacón, I.; Flaccomio, E.; Sciortino, S.; Micela, G.; Reale, F.

    2016-05-01

    Context. The extension of the corona of classical T Tauri stars (CTTS) is is being widely discussed. The standard model of magnetic configuration of CTTS predicts that coronal magnetic flux tubes connect the stellar atmosphere to the inner region of the disk. However, differential rotation may disrupt these long loops. The results from hydrodynamic modeling of X-ray flares observed in CTTS that confirm the star-disk connection hypothesis are still controversial. Some authors suggest the presence of the accretion disk prevents the stellar corona extending beyond the co-rotation radius, while others are simply not confident with the methods used to derive loop lengths. Aims: We use independent procedures to determine the length of flaring loops in stars of the Orion Nebula Cluster, which has previously been analyzed using hydrodynamic models. Our aim is to disentangle the two scenarios that have been proposed. Methods: We present a different approach for determining the length of flaring loops that is based on the oscillatory nature of the loops after strong flares. We use wavelet tools to reveal oscillations during several flares. The subsequent analysis of these oscillations is based on the physics of coronal seismology. Results: Our results likely confirm the large extension of the corona of CTTS and the hypothesis of star-disk magnetic interaction in at least three CTTS of the Orion Nebula Cluster. Conclusions: Analyzing oscillations in flaring events is a powerful tool to determine the physical characteristics of magnetic loops in coronae in stars other than the Sun. The results presented in this work confirm the star-disk magnetic connection in CTTS.

  6. Comparative proteomic analysis reveals mechanistic insights into Pseudomonas putida F1 growth on benzoate and citrate

    PubMed Central

    2013-01-01

    Pseudomonas species are capable to proliferate under diverse environmental conditions and thus have a significant bioremediation potential. To enhance our understanding of their metabolic versatility, this study explores the changes in the proteome and physiology of Pseudomonas putida F1 resulting from its growth on benzoate, a moderate toxic compound that can be catabolized, and citrate, a carbon source that is assimilated through central metabolic pathways. A series of repetitive batch cultivations were performed to ensure a complete adaptation of the bacteria to each of these contrasting carbon sources. After several growth cycles, cell growth stabilized at the maximum level and exhibited a reproducible growth profile. The specific growth rates measured for benzoate (1.01 ± 0.11 h-1) and citrate (1.11 ± 0.12 h-1) were similar, while a higher yield was observed for benzoate (0.6 and 0.3 g cell mass per g of benzoate and citrate, respectively), reflecting the different degrees of carbon reduction in the two substrates. Comparative proteomic analysis revealed an enrichment of several oxygenases/dehydrogenases in benzoate-grown cells, indicative of the higher carbon reduction of benzoate. Moreover, the upregulation of all 14 proteins implicated in benzoate degradation via the catechol ortho-cleavage pathway was observed, while several stress-response proteins were increased to aid cells to cope with benzoate toxicity. Unexpectedly, citrate posed more challenges than benzoate in the maintenance of pH homeostasis, as indicated by the enhancement of the Na+/H+ antiporter and carbonic anhydrase. The study provides important mechanistic insights into Pseudomonas adaptation to varying carbon sources that are of great relevance to bioremediation efforts. PMID:24156539

  7. Multimodal and Multi-tissue Measures of Connectivity Revealed by Joint Independent Component Analysis

    PubMed Central

    Ling, Josef; Caprihan, Arvind; Calhoun, Vince D.; Jung, Rex E.; Heileman, Gregory L.

    2009-01-01

    The human brain functions as an efficient system where signals arising from gray matter are transported via white matter tracts to other regions of the brain to facilitate human behavior. However, with a few exceptions, functional and structural neuroimaging data are typically optimized to maximize the quantification of signals arising from a single source. For example, functional magnetic resonance imaging (FMRI) is typically used as an index of gray matter functioning whereas diffusion tensor imaging (DTI) is typically used to determine white matter properties. While it is likely that these signals arising from different tissue sources contain complementary information, the signal processing algorithms necessary for the fusion of neuroimaging data across imaging modalities are still in a nascent stage. In the current paper we present a data-driven method for combining measures of functional connectivity arising from gray matter sources (FMRI resting state data) with different measures of white matter connectivity (DTI). Specifically, a joint independent component analysis (J-ICA) was used to combine these measures of functional connectivity following intensive signal processing and feature extraction within each of the individual modalities. Our results indicate that one of the most predominantly used measures of functional connectivity (activity in the default mode network) is highly dependent on the integrity of white matter connections between the two hemispheres (corpus callosum) and within the cingulate bundles. Importantly, the discovery of this complex relationship of connectivity was entirely facilitated by the signal processing and fusion techniques presented herein and could not have been revealed through separate analyses of both data types as is typically performed in the majority of neuroimaging experiments. We conclude by discussing future applications of this technique to other areas of neuroimaging and examining potential limitations of the

  8. Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential.

    PubMed

    Holmes, Neil A; Innocent, Tabitha M; Heine, Daniel; Bassam, Mahmoud Al; Worsley, Sarah F; Trottmann, Felix; Patrick, Elaine H; Yu, Douglas W; Murrell, J C; Schiøtt, Morten; Wilkinson, Barrie; Boomsma, Jacobus J; Hutchings, Matthew I

    2016-01-01

    The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis

  9. Emergence of Hepatitis C Virus Genotype 4: Phylogenetic Analysis Reveals Three Distinct Epidemiological Profiles ▿

    PubMed Central

    de Bruijne, Joep; Schinkel, Janke; Prins, Maria; Koekkoek, Sylvie M.; Aronson, Sem J.; van Ballegooijen, Marijn W.; Reesink, Hendrik W.; Molenkamp, Richard; van de Laar, Thijs J. W.

    2009-01-01

    Hepatitis C virus (HCV) genotype 4 (HCV-4) infection is considered to be difficult to treat and has become increasingly prevalent in European countries, including The Netherlands. Using a molecular epidemiological approach, the present study investigates the genetic diversity and evolutionary origin of HCV-4 in Amsterdam, The Netherlands. Phylogenetic analysis of the NS5B sequences (668 bp) obtained from 133 patients newly diagnosed with HCV-4 infection over the period from 1999 to 2008 revealed eight distinct HCV-4 subtypes; the majority of HCV-4 isolates were of subtypes 4d (57%) and 4a (37%). Three distinct monophyletic clusters were identified, with each one having a specific epidemiological profile: (i) Egyptian immigrants infected with HCV-4a (n = 46), (ii) Dutch patients with a history of injecting drug use infected with HCV-4d (n = 44), and (iii) Dutch human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) infected with HCV-4d (n = 26). Subsequent molecular clock analyses confirmed that the emergence of HCV-4 within these three risk groups coincided with (i) the parenteral antischistosomal therapy campaigns in Egypt (1920 to 1960), (ii) the popularity of injecting drug use in The Netherlands (1960 to 1990), and (iii) the rise in high-risk sexual behavior among MSM after the introduction of highly active antiretroviral therapy (1996 onwards). Our data show that in addition to the influx of HCV-4 strains from countries where HCV-4 is endemic, the local spread of HCV-4d affecting injecting drug users and, in recent years, especially HIV-positive MSM will further increase the relative proportion of HCV-4-infected patients in The Netherlands. HCV-4-specific agents are drastically needed to improve treatment response rates and decrease the future burden of HCV-4-related disease. PMID:19794040

  10. Genome Analysis of Two Pseudonocardia Phylotypes Associated with Acromyrmex Leafcutter Ants Reveals Their Biosynthetic Potential

    PubMed Central

    Holmes, Neil A.; Innocent, Tabitha M.; Heine, Daniel; Bassam, Mahmoud Al; Worsley, Sarah F.; Trottmann, Felix; Patrick, Elaine H.; Yu, Douglas W.; Murrell, J. C.; Schiøtt, Morten; Wilkinson, Barrie; Boomsma, Jacobus J.; Hutchings, Matthew I.

    2016-01-01

    The attine ants of South and Central America are ancient farmers, having evolved a symbiosis with a fungal food crop >50 million years ago. The most evolutionarily derived attines are the Atta and Acromyrmex leafcutter ants, which harvest fresh leaves to feed their fungus. Acromyrmex and many other attines vertically transmit a mutualistic strain of Pseudonocardia and use antifungal compounds made by these bacteria to protect their fungal partner against co-evolved fungal pathogens of the genus Escovopsis. Pseudonocardia mutualists associated with the attines Apterostigma dentigerum and Trachymyrmex cornetzi make novel cyclic depsipeptide compounds called gerumycins, while a mutualist strain isolated from derived Acromyrmex octospinosus makes an unusual polyene antifungal called nystatin P1. The novelty of these antimicrobials suggests there is merit in exploring secondary metabolites of Pseudonocardia on a genome-wide scale. Here, we report a genomic analysis of the Pseudonocardia phylotypes Ps1 and Ps2 that are consistently associated with Acromyrmex ants collected in Gamboa, Panama. These were previously distinguished solely on the basis of 16S rRNA gene sequencing but genome sequencing of five Ps1 and five Ps2 strains revealed that the phylotypes are distinct species and each encodes between 11 and 15 secondary metabolite biosynthetic gene clusters (BGCs). There are signature BGCs for Ps1 and Ps2 strains and some that are conserved in both. Ps1 strains all contain BGCs encoding nystatin P1-like antifungals, while the Ps2 strains encode novel nystatin-like molecules. Strains show variations in the arrangement of these BGCs that resemble those seen in gerumycin gene clusters. Genome analyses and invasion assays support our hypothesis that vertically transmitted Ps1 and Ps2 strains have antibacterial activity that could help shape the cuticular microbiome. Thus, our work defines the Pseudonocardia species associated with Acromyrmex ants and supports the hypothesis

  11. Comparative methylome analysis in solid tumors reveals aberrant methylation at chromosome 6p in nasopharyngeal carcinoma

    PubMed Central

    Dai, Wei; Cheung, Arthur Kwok Leung; Ko, Josephine Mun Yee; Cheng, Yue; Zheng, Hong; Ngan, Roger Kai Cheong; Ng, Wai Tong; Lee, Anne Wing Mui; Yau, Chun Chung; Lee, Victor Ho Fu; Lung, Maria Li

    2015-01-01

    Altered patterns of DNA methylation are key features of cancer. Nasopharyngeal carcinoma (NPC) has the highest incidence in Southern China. Aberrant methylation at the promoter region of tumor suppressors is frequently reported in NPC; however, genome-wide methylation changes have not been comprehensively investigated. Therefore, we systematically analyzed methylome data in 25 primary NPC tumors and nontumor counterparts using a high-throughput approach with the Illumina HumanMethylation450 BeadChip. Comparatively, we examined the methylome data of 11 types of solid tumors collected by The Cancer Genome Atlas (TCGA). In NPC, the hypermethylation pattern was more dominant than hypomethylation and the majority of de novo methylated loci were within or close to CpG islands in tumors. The comparative methylome analysis reveals hypermethylation at chromosome 6p21.3 frequently occurred in NPC (false discovery rate; FDR=1.33 × 10−9), but was less obvious in other types of solid tumors except for prostate and Epstein–Barr virus (EBV)-positive gastric cancer (FDR<10−3). Bisulfite pyrosequencing results further confirmed the aberrant methylation at 6p in an additional patient cohort. Evident enrichment of the repressive mark H3K27me3 and active mark H3K4me3 derived from human embryonic stem cells were found at these regions, indicating both DNA methylation and histone modification function together, leading to epigenetic deregulation in NPC. Our study highlights the importance of epigenetic deregulation in NPC. Polycomb Complex 2 (PRC2), responsible for H3K27 trimethylation, is a promising therapeutic target. A key genomic region on 6p with aberrant methylation was identified. This region contains several important genes having potential use as biomarkers for NPC detection. PMID:25924914

  12. Transcriptome Analysis of Chilling-Imbibed Embryo Revealed Membrane Recovery Related Genes in Maize

    PubMed Central

    He, Fei; Shen, Hangqi; Lin, Cheng; Fu, Hong; Sheteiwy, Mohamed S.; Guan, Yajing; Huang, Yutao; Hu, Jin

    2017-01-01

    The delayed seed germination and poor seedling growth caused by imbibitional chilling injury was common phenomenon in maize seedling establishment. In this study, RNA sequencing technology was used to comprehensively investigate the gene expressions in chilling-imbibed maize embryo and to reveal the underlying mechanism of chilling injury at molecular level. Imbibed seeds for 2 h at 5°C (LT2) were selected and transcriptomic comparative analysis was performed. Among 327 DEGs indentified between dry seed (CK0) and LT2, 15 specific genes with plasma membrane (PM) relevant functions belonging to lipid metabolism, stress, signaling and transport were characterized, and most of them showed down-regulation pattern under chilling stress. When transferred to 25°C for recovery (LT3), remarkable changes occurred in maize embryo. There were 873 DEGs including many PM related genes being identified between LT2 and LT3, some of which showing significant increase after 1 h recovery. Moreover, 15 genes encoding intracellular vesicular trafficking proteins were found to be exclusively differential expressed at recovery stage. It suggested that the intracellular vesicle trafficking might be essential for PM recovery through PM turnover. Furthermore, transcriptome analyses on imbibed embryos under normal condition (25°C) were also made as a contrast. A total of 651 DEGs were identified to mainly involved in protein metabolism, transcriptional regulation, signaling, and energy productions. Overall, the RNA-Seq results provided us a deep knowledge of imbibitional chilling injury on plasma membrane and a new view on PM repaired mechanism during early seed imbibition at transcriptional level. The DEGs identified in this work would be useful references in future seed germination research. PMID:28101090

  13. Phylogenetic analysis reveals rapid evolutionary dynamics in the plant RNA virus genus tobamovirus.

    PubMed

    Pagán, Israel; Firth, Cadhla; Holmes, Edward C

    2010-10-01

    Early studies on the evolutionary dynamics of plant RNA viruses suggested that they may evolve more slowly than their animal counterparts, sometimes dramatically so. However, these estimates were often based on an assumption of virus-host codivergence over time-scales of many millions of years that is difficult to verify. An important example are viruses of the genus Tobamovirus, where the assumption of host-virus codivergence over 100 million years has led to rate estimates in the range of ~1 × 10(-8) nucleotide substitutions per site, per year. Such a low evolutionary rate is in apparent contradiction with the ability of some tobamoviruses to quickly overcome inbred genetic resistance. To resolve how rapidly molecular evolution proceeds in the tobomaviruses, we estimated rates of nucleotide substitution, times to common ancestry, and the extent of congruence between virus and host phylogenies. Using Bayesian coalescent methods applied to time-stamped sequences, we estimated mean evolutionary rates at the nucleotide and amino acid levels of between 1 × 10(-5) and 1.3 × 10(-3) substitutions per site, per year, and hence similar to those seen in a broad range of animal and plant RNA viruses. Under these rates, a conservative estimate for the time of origin of the sampled tobamoviruses is within the last 100,000 years, and hence a far more recently than proposed assuming codivergence. This is supported by our cophylogeny analysis which revealed significantly discordant evolutionary histories between the tobamoviruses and the plant families they infect.

  14. Comparative Genome Analysis Reveals Metabolic Versatility and Environmental Adaptations of Sulfobacillus thermosulfidooxidans Strain ST

    PubMed Central

    Guo, Xue; Yin, Huaqun; Liang, Yili; Hu, Qi; Zhou, Xishu; Xiao, Yunhua; Ma, Liyuan; Zhang, Xian; Qiu, Guanzhou; Liu, Xueduan

    2014-01-01

    The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant acidophiles within the phylum Firmicutes and requires extremely acidic environments and hypersalinity for optimal growth. However, our understanding of them is still preliminary partly because few genome sequences are available. Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was deciphered to obtain a comprehensive insight into the genetic content and to understand the cellular mechanisms necessary for its survival. Furthermore, the expressions of key genes related with iron and sulfur oxidation were verified by semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of heterogeneity with other Sulfobacillus species. The presence of numerous transposases, genomic islands and complete CRISPR/Cas defence systems testifies to its dynamic evolution consistent with the genome heterogeneity. As expected, S. thermosulfidooxidans encodes a suit of conserved enzymes required for the oxidation of inorganic sulfur compounds (ISCs). The model of sulfur oxidation in S. thermosulfidooxidans was proposed, which showed some different characteristics from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase reductase and heterodisulfide reductase were suggested to play important roles in the sulfur oxidation. Although the iron oxidation ability was observed, some key proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a predicted sulfocyanin is proposed to transfer electrons in the iron oxidation. Furthermore, its carbon metabolism is rather flexible, can perform the transformation of pentose through the oxidative and non-oxidative pentose phosphate pathways and has the ability to take up small organic compounds. It encodes a multitude of heavy metal resistance systems to

  15. Multivariate pattern analysis reveals anatomical connectivity differences between the left and right mesial temporal lobe epilepsy.

    PubMed

    Fang, Peng; An, Jie; Zeng, Ling-Li; Shen, Hui; Chen, Fanglin; Wang, Wensheng; Qiu, Shijun; Hu, Dewen

    2015-01-01

    Previous studies have demonstrated differences of clinical signs and functional brain network organizations between the left and right mesial temporal lobe epilepsy (mTLE), but the anatomical connectivity differences underlying functional variance between the left and right mTLE remain uncharacterized. We examined 43 (22 left, 21 right) mTLE patients with hippocampal sclerosis and 39 healthy controls using diffusion tensor imaging. After the whole-brain anatomical networks were constructed for each subject, multivariate pattern analysis was applied to classify the left mTLE from the right mTLE and extract the anatomical connectivity differences between the left and right mTLE patients. The classification results reveal 93.0% accuracy for the left mTLE versus the right mTLE, 93.4% accuracy for the left mTLE versus controls and 90.0% accuracy for the right mTLE versus controls. Compared with the right mTLE, the left mTLE exhibited a different connectivity pattern in the cortical-limbic network and cerebellum. The majority of the most discriminating anatomical connections were located within or across the cortical-limbic network and cerebellum, thereby indicating that these disease-related anatomical network alterations may give rise to a portion of the complex of emotional and memory deficit between the left and right mTLE. Moreover, the orbitofrontal gyrus, cingulate cortex, hippocampus and parahippocampal gyrus, which exhibit high discriminative power in classification, may play critical roles in the pathophysiology of mTLE. The current study demonstrated that anatomical connectivity differences between the left mTLE and the right mTLE may have the potential to serve as a neuroimaging biomarker to guide personalized diagnosis of the left and right mTLE.

  16. Image Restoration and Analysis of Influenza Virions Binding to Membrane Receptors Reveal Adhesion-Strengthening Kinetics

    PubMed Central

    Lee, Donald W.; Hsu, Hung-Lun; Bacon, Kaitlyn B.; Daniel, Susan

    2016-01-01

    With the development of single-particle tracking (SPT) microscopy and host membrane mimics called supported lipid bilayers (SLBs), stochastic virus-membrane binding interactions can be studied in depth while maintaining control over host receptor type and concentration. However, several experimental design challenges and quantitative image analysis limitations prevent the widespread use of this approach. One main challenge of SPT studies is the low signal-to-noise ratio of SPT videos, which is sometimes inevitable due to small particle sizes, low quantum yield of fluorescent dyes, and photobleaching. These situations could render current particle tracking software to yield biased binding kinetic data caused by intermittent tracking error. Hence, we developed an effective image restoration algorithm for SPT applications called STAWASP that reveals particles with a signal-to-noise ratio of 2.2 while preserving particle features. We tested our improvements to the SPT binding assay experiment and imaging procedures by monitoring X31 influenza virus binding to α2,3 sialic acid glycolipids. Our interests lie in how slight changes to the peripheral oligosaccharide structures can affect the binding rate and residence times of viruses. We were able to detect viruses binding weakly to a glycolipid called GM3, which was undetected via assays such as surface plasmon resonance. The binding rate was around 28 folds higher when the virus bound to a different glycolipid called GD1a, which has a sialic acid group extending further away from the bilayer surface than GM3. The improved imaging allowed us to obtain binding residence time distributions that reflect an adhesion-strengthening mechanism via multivalent bonds. We empirically fitted these distributions using a time-dependent unbinding rate parameter, koff, which diverges from standard treatment of koff as a constant. We further explain how to convert these models to fit ensemble-averaged binding data obtained by assays such

  17. Transcriptome analysis reveals strong and complex antiviral response in a mollusc.

    PubMed

    He, Yan; Jouaux, Aude; Ford, Susan E; Lelong, Christophe; Sourdaine, Pascal; Mathieu, Michel; Guo, Ximing

    2015-09-01

    Viruses are highly abundant in the oceans, and how filter-feeding molluscs without adaptive immunity defend themselves against viruses is not well understood. We studied the response of a mollusc Crassostrea gigas to Ostreid herpesvirus 1 µVar (OsHV-1μVar) infections using transcriptome sequencing. OsHV-1μVar can replicate extremely rapidly after challenge of C. gigas as evidenced by explosive viral transcription and DNA synthesis, which peaked at 24 and 48 h post-inoculation, respectively, accompanied by heavy oyster mortalities. At 120 h post-injection, however, viral gene transcription and DNA load, and oyster mortality, were greatly reduced indicating an end of active infections and effective control of viral replication in surviving oysters. Transcriptome analysis of the host revealed strong and complex responses involving the activation of all major innate immune pathways that are equipped with expanded and often novel receptors and adaptors. Novel Toll-like receptor (TLR) and MyD88-like genes lacking essential domains were highly up-regulated in the oyster, possibly interfering with TLR signal transduction. RIG-1/MDA5 receptors for viral RNA, interferon-regulatory factors, tissue necrosis factors and interleukin-17 were highly activated and likely central to the oyster's antiviral response. Genes related to anti-apoptosis, oxidation, RNA and protein destruction were also highly up-regulated, while genes related to anti-oxidation were down-regulated. The oxidative burst induced by the up-regulation of oxidases and severe down-regulation of anti-oxidant genes may be important for the destruction of viral components, but may also exacerbate oyster mortality. This study provides unprecedented insights into antiviral response in a mollusc. The mobilization and complex regulation of expanded innate immune-gene families highlights the oyster genome's adaptation to a virus-rich marine environment.

  18. Lipidomic analysis reveals a radiosensitizing role of gamma-linolenic acid in glioma cells.

    PubMed

    Antal, Otilia; Péter, Mária; Hackler, László; Mán, Imola; Szebeni, Gábor; Ayaydin, Ferhan; Hideghéty, Katalin; Vigh, László; Kitajka, Klára; Balogh, Gábor; Puskás, Laszló G

    2015-09-01

    Previous studies have demonstrated that gamma-linolenic acid (GLA) is effective against glioma cells under both in vitro and in vivo conditions. In the present study we determined how GLA alone or in combination with irradiation alters the fatty acid (FA) and lipid profiles, the lipid droplet (LD) content, the lipid biosynthetic gene expression and the apoptosis of glioma cells. In GLA-treated cells direct correlations were found between the levels of various FAs and the expression of the corresponding FA biosynthetic genes. The total levels of saturated and monosaturated FAs decreased in concert with the down-regulation of FASN and SCD1 gene expression. Similarly, decreased FADS1 gene expression was paralleled by lowered arachidonic acid (20:4 n-6) and eicosapentaenoic acid (20:5 n-3) contents, while the down-regulation of FADS2 expression was accompanied by a diminished docosahexaenoic acid (22:6 n-3) content. Detailed mass spectrometric analyses revealed that individual treatments gave rise to distinct lipidomic fingerprints. Following uptake, GLA was subjected to elongation, resulting in dihomo-gamma-linolenic acid (20:3 n-6, DGLA), which was used for the synthesis of the LD constituent triacylglycerols and cholesteryl esters. Accordingly, an increased number of LDs were observed in response to GLA administration after irradiation. GLA increased the radioresponsiveness of U87 MG cells, as demonstrated by an increase in the number of apoptotic cells determined by FACS analysis. In conclusion, treatment with GLA increased the apoptosis of irradiated glioma cells, and GLA might therefore increase the therapeutic efficacy of irradiation in the treatment of gliomas.

  19. Transcriptomic analysis of toxoplasma development reveals many novel functions and structures specific to sporozoites and oocysts.

    PubMed

    Fritz, Heather M; Buchholz, Kerry R; Chen, Xiucui; Durbin-Johnson, Blythe; Rocke, David M; Conrad, Patricia A; Boothroyd, John C

    2012-01-01

    Sexual reproduction of Toxoplasma gondii occurs exclusively within enterocytes of the definitive felid host. The resulting immature oocysts are excreted into the environment during defecation, where in the days following, they undergo a complex developmental process. Within each oocyst, this culminates in the generation of two sporocysts, each containing 4 sporozoites. A single felid host is capable of shedding millions of oocysts, which can survive for years in the environment, are resistant to most methods of microbial inactivation during water-treatment and are capable of producing infection in warm-blooded hosts at doses as low as 1-10 ingested oocysts. Despite its extremely interesting developmental biology and crucial role in initiating an infection, almost nothing is known about the oocyst stage beyond morphological descriptions. Here, we present a complete transcriptomic analysis of the oocyst from beginning to end of its development. In addition, and to identify genes whose expression is unique to this developmental form, we compared the transcriptomes of developing oocysts with those of in vitro-derived tachyzoites and in vivo-derived bradyzoites. Our results reveal many genes whose expression is specifically up- or down-regulated in different developmental stages, including many genes that are likely critical to oocyst development, wall formation, resistance to environmental destruction and sporozoite infectivity. Of special note is the up-regulation of genes that appear "off" in tachyzoites and bradyzoites but that encode homologues of proteins known to serve key functions in those asexual stages, including a novel pairing of sporozoite-specific paralogues of AMA1 and RON2, two proteins that have recently been shown to form a crucial bridge during tachyzoite invasion of host cells. This work provides the first in-depth insight into the development and functioning of one of the most important but least studied stages in the Toxoplasma life cycle.

  20. Revealing the prehistoric settlement of Australia by Y chromosome and mtDNA analysis

    PubMed Central

    Hudjashov, Georgi; Kivisild, Toomas; Underhill, Peter A.; Endicott, Phillip; Sanchez, Juan J.; Lin, Alice A.; Shen, Peidong; Oefner, Peter; Renfrew, Colin; Villems, Richard; Forster, Peter

    2007-01-01

    Published and new samples of Aboriginal Australians and Melanesians were analyzed for mtDNA (n = 172) and Y variation (n = 522), and the resulting profiles were compared with the branches known so far within the global mtDNA and the Y chromosome tree. (i) All Australian lineages are confirmed to fall within the mitochondrial founder branches M and N and the Y chromosomal founders C and F, which are associated with the exodus of modern humans from Africa ≈50–70,000 years ago. The analysis reveals no evidence for any archaic maternal or paternal lineages in Australians, despite some suggestively robust features in the Australian fossil record, thus weakening the argument for continuity with any earlier Homo erectus populations in Southeast Asia. (ii) The tree of complete mtDNA sequences shows that Aboriginal Australians are most closely related to the autochthonous populations of New Guinea/Melanesia, indicating that prehistoric Australia and New Guinea were occupied initially by one and the same Palaeolithic colonization event ≈50,000 years ago, in agreement with current archaeological evidence. (iii) The deep mtDNA and Y chromosomal branching patterns between Australia and most other populations around the Indian Ocean point to a considerable isolation after the initial arrival. (iv) We detect only minor secondary gene flow into Australia, and this could have taken place before the land bridge between Australia and New Guinea was submerged ≈8,000 years ago, thus calling into question that certain significant developments in later Australian prehistory (the emergence of a backed-blade lithic industry, and the linguistic dichotomy) were externally motivated. PMID:17496137

  1. Sr Isotope Analysis of Lacustrine Fossils Reveals Paleohydrological Reorganisation in the Turkana Basin Through the Holocene.

    NASA Astrophysics Data System (ADS)

    Vonhof, H.; Lubbe, J. V. D.; Joordens, J. J.; Feibel, C. S.; Junginger, A.; Garcin, Y.; Krause-Nehring, J.; Beck, C.; Johnson, T. C.

    2015-12-01

    Lake Turkana in northern Kenya is one of the largest lakes in the East African Rift System (EARS) that experienced significant climate-driven lake level variation over the Holocene. Arguably the most important feature of Holocene climate change in the EARS is the termination of the African Humid Period (AHP), that caused a ~70 meter lake level drop in Lake Turkana. The precise hydrological response to the termination of the AHP is potentially complex, because Lake Turkana lies at the cross roads of two large atmospheric convection systems; the Intertropical Convergence Zone (ITCZ) and the Congo Air Boundary (CAB). Shifting of these atmospheric systems around the end of the AHP dramatically rearranged spatial rainfall patterns in the Turkana Basin catchment, causing changes in relative runoff contributions from the different sub-catchments in the Turkana Basin. We here present a Holocene Turkana lake water Sr-isotope reconstruction, based on the analysis of well-dated lacustrine ostracods and shells. This reconstruction reveals consistently high Sr isotope values for the early Holocene, followed by a remarkable drop of Sr isotope ratios around the AHP termination. We interpret this pattern to represent a westward shift in the location of the CAB, leading to the reduction and eventual shutdown of runoff contribution from the Chew Bahir Basin to the Turkana Basin at the end of the AHP. The record demonstrates the exceptional suitability of Sr isotope data for this type of paleohydrological reconstructions. This is mainly due to the chemically conservative Sr-isotope mass balance in EARS lake systems, which is insensitive to environmental change at seasonal timescales that so often overprints the longer term climate signal in stable (oxygen and carbon) isotope records of these lakes. Furthermore, when Sr-isotope signatures of the contributing sub-catchments are known, the observed Sr isotope trends can be interpreted in terms of spatial shifts in climate driven runoff

  2. Diversity in a Polymicrobial Community Revealed by Analysis of Viromes, Endolysins and CRISPR Spacers

    PubMed Central

    Treangen, Todd J.; Koren, Sergey; Pop, Mihai; Bhaya, Devaki

    2016-01-01

    The polymicrobial biofilm communities in Mushroom and Octopus Spring in Yellowstone National Park (YNP) are well characterized, yet little is known about the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2–13), Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1, contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage predators. To analyze phage populations from Octopus Spring biofilms, we sequenced a viral enriched fraction. To assemble and analyze phage metagenomic data, we developed a custom module, VIRITAS, implemented within the MetAMOS framework. This module bins contigs into groups based on tetranucleotide frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this pipeline we were able to assemble phage sequences into contigs and bin them into three clusters that corroborated with their potential host range. The virome contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a recognizable Pfam domain while the rest were hypothetical. Of the recognized domains with CRISPR spacer matches, was the phage endolysin used by lytic phage to disrupt cells. Analysis of the endolysins present in the thermophilic cyanophage contigs revealed a subset of characterized endolysins as well as a Glyco_hydro_108 (PF05838) domain not previously associated with sequenced cyanophages. A search for CRISPR spacer matches to all identified phage endolysins demonstrated that a majority of endolysin domains were targets. This strategy provides a general way to link host and phage as endolysins are known to be widely distributed in bacteriophage. Endolysins can also provide information about host cell wall composition and have the additional potential to be used as targets for novel therapeutics. PMID:27611571

  3. An evolutionary analysis of flightin reveals a conserved motif unique and widespread in Pancrustacea.

    PubMed

    Soto-Adames, Felipe N; Alvarez-Ortiz, Pedro; Vigoreaux, Jim O

    2014-01-01

    Flightin is a thick filament protein that in Drosophila melanogaster is uniquely expressed in the asynchronous, indirect flight muscles (IFM). Flightin is required for the structure and function of the IFM and is indispensable for flight in Drosophila. Given the importance of flight acquisition in the evolutionary history of insects, here we study the phylogeny and distribution of flightin. Flightin was identified in 69 species of hexapods in classes Collembola (springtails), Protura, Diplura, and insect orders Thysanura (silverfish), Dictyoptera (roaches), Orthoptera (grasshoppers), Pthiraptera (lice), Hemiptera (true bugs), Coleoptera (beetles), Neuroptera (green lacewing), Hymenoptera (bees, ants, and wasps), Lepidoptera (moths), and Diptera (flies and mosquitoes). Flightin was also found in 14 species of crustaceans in orders Anostraca (water flea), Cladocera (brine shrimp), Isopoda (pill bugs), Amphipoda (scuds, sideswimmers), and Decapoda (lobsters, crabs, and shrimps). Flightin was not identified in representatives of chelicerates, myriapods, or any species outside Pancrustacea (Tetraconata, sensu Dohle). Alignment of amino acid sequences revealed a conserved region of 52 amino acids, referred herein as WYR, that is bound by strictly conserved tryptophan (W) and arginine (R) and an intervening sequence with a high content of tyrosines (Y). This motif has no homologs in GenBank or PROSITE and is unique to flightin and paraflightin, a putative flightin paralog identified in decapods. A third motif of unclear affinities to pancrustacean WYR was observed in chelicerates. Phylogenetic analysis of amino acid sequences of the conserved motif suggests that paraflightin originated before the divergence of amphipods, isopods, and decapods. We conclude that flightin originated de novo in the ancestor of Pancrustacea > 500 MYA, well before the divergence of insects (~400 MYA) and the origin of flight (~325 MYA), and that its IFM-specific function in Drosophila is a more

  4. Comparative Analysis of RNA Families Reveals Distinct Repertoires for Each Domain of Life

    PubMed Central

    Hoeppner, Marc P.; Gardner, Paul P.; Poole, Anthony M.

    2012-01-01

    The RNA world hypothesis, that RNA genomes and catalysts preceded DNA genomes and genetically-encoded protein catalysts, has been central to models for the early evolution of life on Earth. A key part of such models is continuity between the earliest stages in the evolution of life and the RNA repertoires of extant lineages. Some assessments seem consistent with a diverse RNA world, yet direct continuity between modern RNAs and an RNA world has not been demonstrated for the majority of RNA families, and, anecdotally, many RNA functions appear restricted in their distribution. Despite much discussion of the possible antiquity of RNA families, no systematic analyses of RNA family distribution have been performed. To chart the broad evolutionary history of known RNA families, we performed comparative genomic analysis of over 3 million RNA annotations spanning 1446 families from the Rfam 10 database. We report that 99% of known RNA families are restricted to a single domain of life, revealing discrete repertoires for each domain. For the 1% of RNA families/clans present in more than one domain, over half show evidence of horizontal gene transfer (HGT), and the rest show a vertical trace, indicating the presence of a complex protein synthesis machinery in the Last Universal Common Ancestor (LUCA) and consistent with the evolutionary history of the most ancient protein-coding genes. However, with limited interdomain transfer and few RNA families exhibiting demonstrable antiquity as predicted under RNA world continuity, our results indicate that the majority of modern cellular RNA repertoires have primarily evolved in a domain-specific manner. PMID:23133357

  5. Metabolite analysis of Mycobacterium species under aerobic and hypoxic conditions reveals common metabolic traits.

    PubMed

    Drapal, Margit; Wheeler, Paul R; Fraser, Paul D

    2016-08-01

    A metabolite profiling approach has been implemented to elucidate metabolic adaptation at set culture conditions in five Mycobacterium species (two fast- and three slow-growing) with the potential to act as model organisms for Mycobacterium tuberculosis (Mtb). Analysis has been performed over designated growth phases and under representative environments (nutrient and oxygen depletion) experienced by Mtb during infection. The procedure was useful in determining a range of metabolites (60-120 compounds) covering nucleotides, amino acids, organic acids, saccharides, fatty acids, glycerols, -esters, -phosphates and isoprenoids. Among these classes of compounds, key biomarker metabolites, which can act as indicators of pathway/process activity, were identified. In numerous cases, common metabolite traits were observed for all five species across the experimental conditions (e.g. uracil indicating DNA repair). Amino acid content, especially glutamic acid, highlighted the different properties between the fast- and slow-growing mycobacteria studied (e.g. nitrogen assimilation). The greatest similarities in metabolite composition between fast- and slow-growing mycobacteria were apparent under hypoxic conditions. A comparison to previously reported transcriptomic data revealed a strong correlation between changes in transcription and metabolite content. Collectively, these data validate the changes in the transcription at the metabolite level, suggesting transcription exists as one of the predominant modes of cellular regulation in Mycobacterium. Sectors with restricted correlation between metabolites and transcription (e.g. hypoxic cultivation) warrant further study to elucidate and exploit post-transcriptional modes of regulation. The strong correlation between the laboratory conditions used and data derived from in vivo conditions, indicate that the approach applied is a valuable addition to our understanding of cell regulation in these Mycobacterium species.

  6. Comparative genome analysis reveals metabolic versatility and environmental adaptations of Sulfobacillus thermosulfidooxidans strain ST.

    PubMed

    Guo, Xue; Yin, Huaqun; Liang, Yili; Hu, Qi; Zhou, Xishu; Xiao, Yunhua; Ma, Liyuan; Zhang, Xian; Qiu, Guanzhou; Liu, Xueduan

    2014-01-01

    The genus Sulfobacillus is a cohort of mildly thermophilic or thermotolerant acidophiles within the phylum Firmicutes and requires extremely acidic environments and hypersalinity for optimal growth. However, our understanding of them is still preliminary partly because few genome sequences are available. Here, the draft genome of Sulfobacillus thermosulfidooxidans strain ST was deciphered to obtain a comprehensive insight into the genetic content and to understand the cellular mechanisms necessary for its survival. Furthermore, the expressions of key genes related with iron and sulfur oxidation were verified by semi-quantitative RT-PCR analysis. The draft genome sequence of Sulfobacillus thermosulfidooxidans strain ST, which encodes 3225 predicted coding genes on a total length of 3,333,554 bp and a 48.35% G+C, revealed the high degree of heterogeneity with other Sulfobacillus species. The presence of numerous transposases, genomic islands and complete CRISPR/Cas defence systems testifies to its dynamic evolution consistent with the genome heterogeneity. As expected, S. thermosulfidooxidans encodes a suit of conserved enzymes required for the oxidation of inorganic sulfur compounds (ISCs). The model of sulfur oxidation in S. thermosulfidooxidans was proposed, which showed some different characteristics from the sulfur oxidation of Gram-negative A. ferrooxidans. Sulfur oxygenase reductase and heterodisulfide reductase were suggested to play important roles in the sulfur oxidation. Although the iron oxidation ability was observed, some key proteins cannot be identified in S. thermosulfidooxidans. Unexpectedly, a predicted sulfocyanin is proposed to transfer electrons in the iron oxidation. Furthermore, its carbon metabolism is rather flexible, can perform the transformation of pentose through the oxidative and non-oxidative pentose phosphate pathways and has the ability to take up small organic compounds. It encodes a multitude of heavy metal resistance systems to

  7. Comparative analysis of teleost fish genomes reveals preservation of different ancient clock duplicates in different fishes.

    PubMed

    Wang, Han

    2008-06-01

    Clock (Circadian locomotor output cycle kaput) was the first vertebrate circadian clock gene identified in a mouse forward genetics mutagenesis screen. It encodes a bHLH-PAS protein that is highly conserved throughout evolution. Tetrapods also have the second Clock gene, Clock2 or Npas2 (Neuronal PAS domain protein 2). Conversely, the fruit fly, an invertebrate, has only one clock gene. Interrogation of the five teleost fish genome databases revealed that the zebrafish and the Japanese pufferfish (fugu) each have three clock genes, whereas the green spotted pufferfish (tetraodon), the Japanese medaka fish and the three-spine stickleback each have two clock genes. Phylogenetic and splice site analyses indicated that zebrafish and fugu each have two clock1 genes, clock1a and clock1b and one clock2; tetraodon also have clock1a and clock1b but do not have clock2; and medaka and stickleback each have clock1b and one clock2. Genome neighborhood analysis further showed that clock1a/clock1b in zebrafish, fugu and tetraodon is an ancient duplicate. While the dN/dS ratios of these three fish clock duplicates are all <1, indicating that purifying selection has acted upon them; the Tajima relative rate test showed that all three fish clock duplicates have asymmetric evolutionary rates, implicating that one of these duplicates have been under positive selection or relaxed functional constraint. These results support the view that teleost fish clock genes were generated from an ancient genome-wide duplication, and differential gene loss after the duplication resulted in retention of different ancient duplicates in different teleost fishes, which could have contributed to the evolution of the distinct fish circadian clock mechanisms.

  8. Comparative proteomic analysis reveals activation of mucosal innate immune signaling pathways during cholera.

    PubMed

    Ellis, Crystal N; LaRocque, Regina C; Uddin, Taher; Krastins, Bryan; Mayo-Smith, Leslie M; Sarracino, David; Karlsson, Elinor K; Rahman, Atiqur; Shirin, Tahmina; Bhuiyan, Taufiqur R; Chowdhury, Fahima; Khan, Ashraful Islam; Ryan, Edward T; Calderwood, Stephen B; Qadri, Firdausi; Harris, Jason B

    2015-03-01

    Vibrio cholerae O1 is a major cause of acute watery diarrhea in over 50 countries. Evidence suggests that V. cholerae O1 may activate inflammatory pathways, and a recent study of a Bangladeshi population showed that variants in innate immune genes play a role in mediating susceptibility to cholera. We analyzed human proteins present in the small intestine of patients infected with V. cholerae O1 to characterize the host response to this pathogen. We collected duodenal biopsy specimens from patients with acute cholera after stabilization and again 30 days after initial presentation. Peptides extracted from biopsy specimens were sequenced and quantified using label-free mass spectrometry and SEQUEST. Twenty-seven host proteins were differentially abundant between the acute and convalescent stages of infection; the majority of these have known roles in innate defense, cytokine production, and apoptosis. Immunostaining confirmed that two proteins, WARS and S100A8, were more abundant in lamina propria cells during the acute stage of cholera. Analysis of the differentially abundant proteins revealed the activation of key regulators of inflammation by the innate immune system, including Toll-like receptor 4, nuclear factor kappa-light-chain-enhancer of activated B cells, mitogen-activated protein kinases, and caspase-dependent inflammasomes. Interleukin-12β (IL-12β) was a regulator of several proteins that were activated during cholera, and we confirmed that IL-12β was produced by lymphocytes recovered from duodenal biopsy specimens of cholera patients. Our study shows that a broad inflammatory response is generated in the gut early after onset of cholera, which may be critical in the development of long-term mucosal immunity against V. cholerae O1.

  9. Phylogenetic analysis of faecal microbiota from captive cheetahs reveals underrepresentation of Bacteroidetes and Bifidobacteriaceae

    PubMed Central

    2014-01-01

    Background Imbalanced feeding regimes may initiate gastrointestinal and metabolic diseases in endangered felids kept in captivity such as cheetahs. Given the crucial role of the host’s intestinal microbiota in feed fermentation and health maintenance, a better understanding of the cheetah’s intestinal ecosystem is essential for improvement of current feeding strategies. We determined the phylogenetic diversity of the faecal microbiota of the only two cheetahs housed in an EAZA associated zoo in Flanders, Belgium, to gain first insights in the relative distribution, identity and potential role of the major community members. Results Taxonomic analysis of 16S rRNA gene clone libraries (702 clones) revealed a microbiota dominated by Firmicutes (94.7%), followed by a minority of Actinobacteria (4.3%), Proteobacteria (0.4%) and Fusobacteria (0.6%). In the Firmicutes, the majority of the phylotypes within the Clostridiales were assigned to Clostridium clusters XIVa (43%), XI (38%) and I (13%). Members of the Bacteroidetes phylum and Bifidobacteriaceae, two groups that can positively contribute in maintaining intestinal homeostasis, were absent in the clone libraries and detected in only marginal to low levels in real-time PCR analyses. Conclusions This marked underrepresentation is in contrast to data previously reported in domestic cats where Bacteroidetes and Bifidobacteriaceae are common residents of the faecal microbiota. Next to methodological differences, these findings may also reflect the apparent differences in dietary habits of both felid species. Thus, our results question the role of the domestic cat as the best available model for nutritional intervention studies in endangered exotic felids. PMID:24548488

  10. Global transcriptional analysis reveals surface remodeling of Anaplasma marginale in the tick vector

    PubMed Central

    2014-01-01

    Background Pathogens dependent upon vectors for transmission to new hosts undergo environment specific changes in gene transcription dependent on whether they are replicating in the vector or the mammalian host. Differential gene transcription, especially of potential vaccine candidates, is of interest in Anaplasma marginale, the tick-borne causative agent of bovine anaplasmosis. Methods RNA-seq technology allowed a comprehensive analysis of the transcriptional status of A. marginale genes in two conditions: bovine host blood and tick derived cell culture, a model for the tick vector. Quantitative PCR was used to assess transcription of a set of genes in A. marginale infected tick midguts and salivary glands at two time points during the transmission cycle. Results Genes belonging to fourteen pathways or component groups were found to be differentially transcribed in A. marginale in the bovine host versus the tick vector. One of the most significantly altered groups was composed of surface proteins. Of the 56 genes included in the surface protein group, eight were up regulated and 26 were down regulated. The down regulated surface protein encoding genes include several that are well studied due to their immunogenicity and function. Quantitative PCR of a set of genes demonstrated that transcription in tick cell culture most closely approximates transcription in salivary glands of recently infected ticks. Conclusions The ISE6 tick cell culture line is an acceptable model for early infection in tick salivary glands, and reveals disproportionate down regulation of surface protein genes in the tick. Transcriptional profiling in other cell lines may help us simulate additional microenvironments. Understanding vector-specific alteration of gene transcription, especially of surface protein encoding genes, may aid in the development of vaccines or transmission blocking therapies. PMID:24751137

  11. fMRI Analysis-by-Synthesis Reveals a Dorsal Hierarchy That Extracts Surface Slant.

    PubMed

    Ban, Hiroshi; Welchman, Andrew E

    2015-07-08

    The brain's skill in estimating the 3-D orientation of viewed surfaces supports a range of behaviors, from placing an object on a nearby table, to planning the best route when hill walking. This ability relies on integrating depth signals across extensive regions of space that exceed the receptive fields of early sensory neurons. Although hierarchical selection and pooling is central to understanding of the ventral visual pathway, the successive operations in the dorsal stream are poorly understood. Here we use computational modeling of human fMRI signals to probe the computations that extract 3-D surface orientation from binocular disparity. To understand how representations evolve across the hierarchy, we developed an inference approach using a series of generative models to explain the empirical fMRI data in different cortical areas. Specifically, we simulated the responses of candidate visual processing algorithms and tested how well they explained fMRI responses. Thereby we demonstrate a hierarchical refinement of visual representations moving from the representation of edges and figure-ground segmentation (V1, V2) to spatially extensive disparity gradients in V3A. We show that responses in V3A are little affected by low-level image covariates, and have a partial tolerance to the overall depth position. Finally, we show that responses in V3A parallel perceptual judgments of slant. This reveals a relatively short computational hierarchy that captures key information about the 3-D structure of nearby surfaces, and more generally demonstrates an analysis approach that may be of merit in a diverse range of brain imaging domains.

  12. Transcriptome Analysis of the Entomopathogenic Oomycete Lagenidium giganteum Reveals Putative Virulence Factors

    PubMed Central

    Quiroz Velasquez, Paula F.; Abiff, Sumayyah K.; Fins, Katrina C.; Conway, Quincy B.; Salazar, Norma C.; Delgado, Ana Paula; Dawes, Jhanelle K.; Douma, Lauren G.

    2014-01-01

    A combination of 454 pyrosequencing and Sanger sequencing was used to sample and characterize the transcriptome of the entomopathogenic oomycete Lagenidium giganteum. More than 50,000 high-throughput reads were annotated through homology searches. Several selected reads served as seeds for the amplification and sequencing of full-length transcripts. Phylogenetic analyses inferred from full-length cellulose synthase alignments revealed that L giganteum is nested within the peronosporalean galaxy and as such appears to have evolved from a phytopathogenic ancestor. In agreement with the phylogeny reconstructions, full-length L. giganteum oomycete effector orthologs, corresponding to the cellulose-binding elicitor lectin (CBEL), crinkler (CRN), and elicitin proteins, were characterized by domain organizations similar to those of pathogenicity factors of plant-pathogenic oomycetes. Importantly, the L. giganteum effectors provide a basis for detailing the roles of canonical CRN, CBEL, and elicitin proteins in the infectious process of an oomycete known principally as an animal pathogen. Finally, phylogenetic analyses and genome mining identified members of glycoside hydrolase family 5 subfamily 27 (GH5_27) as putative virulence factors active on the host insect cuticle, based in part on the fact that GH5_27 genes are shared by entomopathogenic oomycetes and fungi but are underrepresented in nonentomopathogenic genomes. The genomic resources gathered from the L. giganteum transcriptome analysis strongly suggest that filamentous entomopathogens (oomycetes and fungi) exhibit convergent evolution: they have evolved independently from plant-associated microbes, have retained genes indicative of plant associations, and may share similar cores of virulence factors, such as GH5_27 enzymes, that are absent from the genomes of their plant-pathogenic relatives. PMID:25107973

  13. Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces

    PubMed Central

    Engin, H. Billur; Kreisberg, Jason F.; Carter, Hannah

    2016-01-01

    Recently it has been shown that cancer mutations selectively target protein-protein interactions. We hypothesized that mutations affecting distinct protein interactions involving established cancer genes could contribute to tumor heterogeneity, and that novel mechanistic insights might be gained into tumorigenesis by investigating protein interactions under positive selection in cancer. To identify protein interactions under positive selection in cancer, we mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896 experimentally determined protein structures and analyzed their spatial distribution. In total, 20% of mutations on the surface of known cancer genes perturbed protein-protein interactions (PPIs), and this enrichment for PPI interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value < 10−4) and oncogenes (Odds Ratio 1.17, P-value < 10−3). To study this further, we constructed a bipartite network representing structurally resolved PPIs from all available human complexes in the Protein Data Bank (2,864 proteins, 3,072 PPIs). Analysis of frequently mutated cancer genes within this network revealed that tumor-suppressors, but not oncogenes, are significantly enriched with functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value < 10−8). We present two important examples, TP53 and beta-2-microglobulin, for which the patterns of somatic mutations at interfaces provide insights into specifically perturbed biological circuits. In patients with TP53 mutations, patient survival correlated with the specific interactions that were perturbed. Moreover, we investigated mutations at the interface of protein-nucleotide interactions and observed an unexpected number of missense mutations but not silent mutations occurring within DNA and RNA binding sites. Finally, we provide a resource of 3,072 PPI interfaces ranked according to their mutation rates. Analysis of this list highlights 282 novel candidate cancer

  14. Synaptic protein ubiquitination in rat brain revealed by antibody-based ubiquitome analysis.

    PubMed

    Na, Chan Hyun; Jones, Drew R; Yang, Yanling; Wang, Xusheng; Xu, Yanji; Peng, Junmin

    2012-09-07

    Protein ubiquitination is an essential post-translational modification regulating neurodevelopment, synaptic plasticity, learning, and memory, and its dysregulation contributes to the pathogenesis of neurological diseases. Here we report a systematic analysis of ubiquitinated proteome (ubiquitome) in rat brain using a newly developed monoclonal antibody that recognizes the diglycine tag on lysine residues in trypsinized peptides (K-GG peptides). Initial antibody specificity analysis showed that the antibody can distinguish K-GG peptides from linear GG peptides or pseudo K-GG peptides derived from iodoacetamide. To evaluate the false discovery rate of K-GG peptide matches during database search, we introduced a null experiment using bacterial lysate that contains no such peptides. The brain ubiquitome was then analyzed by this antibody enrichment with or without strong cation exchange (SCX) prefractionation. During SCX chromatography, although the vast majority of K-GG peptides were detected in the fractions containing at least three positive charged peptides, specific K-GG peptides with two positive charges (e.g., protein N-terminal acetylated and C-terminal non-K/R peptides) were also identified in early fractions. The reliability of C-terminal K-GG peptides was also extensively investigated. Finally, we collected a data set of 1786 K-GG sites on 2064 peptides in 921 proteins and estimated their abundance by spectral counting. The study reveals a wide range of ubiquitination events on key components in presynaptic region (e.g., Bassoon, NSF, SNAP25, synapsin, synaptotagmin, and syntaxin) and postsynaptic density (e.g., PSD-95, GKAP, CaMKII, as well as receptors for NMDA, AMPA, GABA, serotonin, and acetylcholine). We also determined ubiquitination sites on amyloid precursor protein and alpha synuclein that are thought to be causative agents in Alzhermer's and Parkinson's disorders, respectively. As K-GG peptides can also be produced from Nedd8 or ISG15 modified

  15. Deep sequencing analysis of the developing mouse brain reveals a novel microRNA

    PubMed Central

    2011-01-01

    Background MicroRNAs (miRNAs) are small non-coding RNAs that can exert multilevel inhibition/repression at a post-transcriptional or protein synthesis level during disease or development. Characterisation of miRNAs in adult mammalian brains by deep sequencing has been reported previously. However, to date, no small RNA profiling of the developing brain has been undertaken using this method. We have performed deep sequencing and small RNA analysis of a developing (E15.5) mouse brain. Results We identified the expression of 294 known miRNAs in the E15.5 developing mouse brain, which were mostly represented by let-7 family and other brain-specific miRNAs such as miR-9 and miR-124. We also discovered 4 putative 22-23 nt miRNAs: mm_br_e15_1181, mm_br_e15_279920, mm_br_e15_96719 and mm_br_e15_294354 each with a 70-76 nt predicted pre-miRNA. We validated the 4 putative miRNAs and further characterised one of them, mm_br_e15_1181, throughout embryogenesis. Mm_br_e15_1181 biogenesis was Dicer1-dependent and was expressed in E3.5 blastocysts and E7 whole embryos. Embryo-wide expression patterns were observed at E9.5 and E11.5 followed by a near complete loss of expression by E13.5, with expression restricted to a specialised layer of cells within the developing and early postnatal brain. Mm_br_e15_1181 was upregulated during neurodifferentiation of P19 teratocarcinoma cells. This novel miRNA has been identified as miR-3099. Conclusions We have generated and analysed the first deep sequencing dataset of small RNA sequences of the developing mouse brain. The analysis revealed a novel miRNA, miR-3099, with potential regulatory effects on early embryogenesis, and involvement in neuronal cell differentiation/function in the brain during late embryonic and early neonatal development. PMID:21466694

  16. Properties of galaxies around AGNs with the most massive supermassive black holes revealed by clustering analysis

    NASA Astrophysics Data System (ADS)

    Shirasaki, Yuji; Komiya, Yutaka; Ohishi, Masatoshi; Mizumoto, Yoshihiko

    2016-04-01

    We present results of the clustering analysis between active galactic nuclei (AGNs) and galaxies at redshift 0.1-1.0, which was performed to investigate the properties of galaxies associated with the AGNs and reveal the nature of the fueling mechanism of supermassive black holes (SMBHs). We used 8059 AGNs/quasi-stellar objects (QSOs) for which virial masses of individual SMBHs were measured, and divided them into four mass groups.Cross-correlation analysis was performed to reconfirm our previous result that cross-correlation length increases with SMBH mass MBH; we obtained consistent results. A linear bias of AGN for each mass group was measured as 1.47 for MBH = 107.5-108.2 M⊙ and 3.08 for MBH = 109-1010 M⊙. The averaged color and luminosity distributions of galaxies around the AGNs/QSOs were also derived for each mass group. The galaxy color Dopt-IR was estimated from a spectral energy distribution (SED) constructed from a catalog derived by merging the Sloan Digital Sky Survey (SDSS) and the UKIRT Infrared Deep Sky Survey (UKIDSS) catalogs. The distributions of color and luminosity were derived by a subtraction method, which does not require redshift information of galaxies. The main results of this work are as follows. (1) A linear bias increases by a factor of two from the lower-mass group to the highest-mass group. (2) The environment around AGNs with the most massive SMBHs (MBH > 109 M⊙) is dominated by red sequence galaxies. (3) Marginal indication of decline in luminosity function at dimmer side of MIR > -19.5 is found for galaxies around AGNs with MBH = 108.2-109 M⊙ and nearest redshift group (z = 0.1-0.3). These results indicate that AGNs with the most massive SMBHs reside in haloes where a large fraction of galaxies have been transited to the red sequence. The accretion of hot halo gas as well as recycled gas from evolving stars can be one of the plausible mechanisms to fuel the SMBHs above ˜ 109 M⊙.

  17. Structure-Based Analysis Reveals Cancer Missense Mutations Target Protein Interaction Interfaces.

    PubMed

    Engin, H Billur; Kreisberg, Jason F; Carter, Hannah

    2016-01-01

    Recently it has been shown that cancer mutations selectively target protein-protein interactions. We hypothesized that mutations affecting distinct protein interactions involving established cancer genes could contribute to tumor heterogeneity, and that novel mechanistic insights might be gained into tumorigenesis by investigating protein interactions under positive selection in cancer. To identify protein interactions under positive selection in cancer, we mapped over 1.2 million nonsynonymous somatic cancer mutations onto 4,896 experimentally determined protein structures and analyzed their spatial distribution. In total, 20% of mutations on the surface of known cancer genes perturbed protein-protein interactions (PPIs), and this enrichment for PPI interfaces was observed for both tumor suppressors (Odds Ratio 1.28, P-value < 10(-4)) and oncogenes (Odds Ratio 1.17, P-value < 10(-3)). To study this further, we constructed a bipartite network representing structurally resolved PPIs from all available human complexes in the Protein Data Bank (2,864 proteins, 3,072 PPIs). Analysis of frequently mutated cancer genes within this network revealed that tumor-suppressors, but not oncogenes, are significantly enriched with functional mutations in homo-oligomerization regions (Odds Ratio 3.68, P-Value < 10(-8)). We present two important examples, TP53 and beta-2-microglobulin, for which the patterns of somatic mutations at interfaces provide insights into specifically perturbed biological circuits. In patients with TP53 mutations, patient survival correlated with the specific interactions that were perturbed. Moreover, we investigated mutations at the interface of protein-nucleotide interactions and observed an unexpected number of missense mutations but not silent mutations occurring within DNA and RNA binding sites. Finally, we provide a resource of 3,072 PPI interfaces ranked according to their mutation rates. Analysis of this list highlights 282 novel candidate cancer

  18. No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects

    PubMed Central

    Jones, Aksana Kaefer; Santini-Oliveira, Marilia; Taylor, Graham P.; Patterson, Kristine B.; Nilius, Angela M.; Klein, Cheri Enders

    2015-01-01

    Lopinavir-ritonavir is frequently prescribed to HIV-1-infected women during pregnancy. Decreased lopinavir exposure has been reported during pregnancy, but the clinical significance of this reduction is uncertain. This analysis aimed to evaluate the need for lopinavir dose adjustment during pregnancy. We conducted a population pharmacokinetic analysis of lopinavir and ritonavir concentrations collected from 84 pregnant and 595 nonpregnant treatment-naive and -experienced HIV-1-infected subjects enrolled in six clinical studies. Lopinavir-ritonavir doses in the studies ranged between 400/100 and 600/150 mg twice daily. In addition, linear mixed-effect analysis was used to compare the area under the concentration-time curve from 0 to 12 h (AUC0–12) and concentration prior to dosing (Cpredose) in pregnant women and nonpregnant subjects. The relationship between lopinavir exposure and virologic suppression in pregnant women and nonpregnant subjects was evaluated. Population pharmacokinetic analysis estimated 17% higher lopinavir clearance in pregnant women than in nonpregnant subjects. Lopinavir clearance values postpartum were 26.4% and 37.1% lower than in nonpregnant subjects and pregnant women, respectively. As the tablet formulation was estimated to be 20% more bioavailable than the capsule formulation, no statistically significant differences between lopinavir exposure in pregnant women receiving the tablet formulation and nonpregnant subjects receiving the capsule formulation were identified. In the range of lopinavir AUC0–12 or Cpredose values observed in the third trimester, there was no correlation between lopinavir exposure and viral load or proportion of subjects with virologic suppression. Similar efficacy was observed between pregnant women and nonpregnant subjects receiving lopinavir-ritonavir at 400/100 mg twice daily. The pharmacokinetic and pharmacodynamic results support the use of a lopinavir-ritonavir 400/100-mg twice-daily dose during pregnancy

  19. The mis-specification of the expected rescaled adjusted range

    NASA Astrophysics Data System (ADS)

    Ellis, Craig

    2006-05-01

    Rescaled range analysis has regained popularity in the recent econophysics literature as a means of identifying long-term dependence in time-series data. Conclusions derived from the rescaled adjusted range statistic are conditional however upon the choice of an appropriate benchmark against which calculated results can be compared. One recent paper in Physica A by Couillard and Davison [Physica A 348 (2005) 404] concludes that the Anis and Lloyd [Biometrika 63 (1976) 111] model of the expected rescaled adjusted range is more accurate than that proposed by Peters [Fractal Market Analysis, Wiley, New York, 1994]. This finding is contrary to the evidence presented by Peters. This paper reveals significant inconsistencies in the empirical results reported by Peters, which when considered, support the conclusions of Couillard and Davison and explain the apparent contradiction in their results versus those of Peters.

  20. Factors Affecting the Academic and Cultural Adjustment of Saudi International Students in Australian Universities

    ERIC Educational Resources Information Center

    Alsahafi, Nisreen; Shin, Seong-Chul

    2017-01-01

    The authors investigate factors affecting Saudi students' educational experiences in Australian universities and their adjustment issues. The data comes from the survey of 100 Saudi international students in Sydney and subsequent interviews. The analysis revealed that language proficiency is the main barrier to Saudi students' academic and social…

  1. Somali Women's Reflections on the Adjustment of Their Children in the United States

    ERIC Educational Resources Information Center

    Nilsson, Johanna E.; Barazanji, Danah M.; Heintzelman, Ashley; Siddiqi, Mubeena; Shilla, Yasmine

    2012-01-01

    Somali women were interviewed regarding their children's adjustment. Qualitative analysis revealed 5 themes: cultural comparisons, concerns about children, parents' loss of disciplinary authority, available support, and the future. The women discussed changes in their children, such as loss of respect and threats to use law enforcement against…

  2. Transcriptome Analysis Reveals Regulation of Gene Expression for Lipid Catabolism in Young Broilers by Butyrate Glycerides

    PubMed Central

    Yin, Fugui; Yu, Hai; Lepp, Dion; Shi, Xuejiang; Yang, Xiaojian; Hu, Jielun; Leeson, Steve; Yang, Chengbo; Nie, Shaoping; Hou, Yongqing; Gong, Joshua

    2016-01-01

    indicated that dietary BG intervention induced 79 and 205 characterized DEGs in the jejunum and liver, respectively. In addition, 255 and 165 TSEGs were detected in the liver and jejunum of BG-fed group, while 162 and 211 TSEGs genes were observed in the liver and jejunum of BD-fed birds, respectively. Bioinformatic analysis with both IPA and DAVID-BR further revealed a significant enrichment of DEGs and TSEGs in the biological processes for reducing the synthesis, storage, transportation and secretion of lipids in the jejunum, while those in the liver were for enhancing the oxidation of ingested lipids and fatty acids. In particular, transcriptional regulators of THRSP and EGR-1 as well as several DEGs involved in the PPAR-α signaling pathway were significantly induced by dietary BG intervention for lipid catabolism. Conclusions Our results demonstrate that BG reduces body fat deposition via regulation of gene expression, which is involved in the biological events relating to the reduction of synthesis, storage, transportation and secretion, and improvement of oxidation of lipids and fatty acids. PMID:27508934

  3. Critical taper analysis reveals lithological control of variations in detachment strength: An analysis of the Alpine basal detachment (Swiss Alps)

    NASA Astrophysics Data System (ADS)

    von Hagke, C.; Oncken, O.; Evseev, S.

    2014-01-01

    Although evidence for weak detachments underlying foreland thrust belts exists, very little is known about the lateral variations in effective strength, as well as the geological nature of such variations. Using critical taper analysis, we show that a detailed and systematic measurement of surface slope of the Central European Alps reveals variations in strength parameter F along the detachment, based on the argument that the Alps are close to the critical state. We show that the basal detachment is very weak near the deformation front but strengthens toward the hinterland. Very low F (effective coefficient of friction plus normalized cohesion) values of <0.1 and even 0.05 occur within evaporites and within shales in Triassic (west) or Upper Cretaceous/Lower Tertiary sequences (east) used by the Alpine sole detachment. These very low values in shales--comparably low values are reported from other orogens--are caused partly by slightly elevated pore pressures (λ > 0.54) but may also require additional mechanisms of dynamic weakening.

  4. Analysis of global gene expression in Brachypodium distachyon reveals extensive network plasticity in response to abiotic stress.

    PubMed

    Priest, Henry D; Fox, Samuel E; Rowley, Erik R; Murray, Jessica R; Michael, Todd P; Mockler, Todd C

    2014-01-01

    Brachypodium distachyon is a close relative of many important cereal crops. Abiotic stress tolerance has a significant impact on productivity of agriculturally important food and feedstock crops. Analysis of the transcriptome of Brachypodium after chilling, high-salinity, drought, and heat stresses revealed diverse differential expression of many transcripts. Weighted Gene Co-Expression Network Analysis revealed 22 distinct gene modules with specific profiles of expression under each stress. Promoter analysis implicated short DNA sequences directly upstream of module members in the regulation of 21 of 22 modules. Functional analysis of module members revealed enrichment in functional terms for 10 of 22 network modules. Analysis of condition-specific correlations between differentially expressed gene pairs revealed extensive plasticity in the expression relationships of gene pairs. Photosynthesis, cell cycle, and cell wall expression modules were down-regulated by all abiotic stresses. Modules which were up-regulated by each abiotic stress fell into diverse and unique gene ontology GO categories. This study provides genomics resources and improves our understanding of abiotic stress responses of Brachypodium.

  5. Remotely Adjustable Hydraulic Pump

    NASA Technical Reports Server (NTRS)

    Kouns, H. H.; Gardner, L. D.

    1987-01-01

    Outlet pressure adjusted to match varying loads. Electrohydraulic servo has positioned sleeve in leftmost position, adjusting outlet pressure to maximum value. Sleeve in equilibrium position, with control land covering control port. For lowest pressure setting, sleeve shifted toward right by increased pressure on sleeve shoulder from servovalve. Pump used in aircraft and robots, where hydraulic actuators repeatedly turned on and off, changing pump load frequently and over wide range.

  6. Adjustable Pitot Probe

    NASA Technical Reports Server (NTRS)

    Ashby, George C., Jr.; Robbins, W. Eugene; Horsley, Lewis A.

    1991-01-01

    Probe readily positionable in core of uniform flow in hypersonic wind tunnel. Formed of pair of mating cylindrical housings: transducer housing and pitot-tube housing. Pitot tube supported by adjustable wedge fairing attached to top of pitot-tube housing with semicircular foot. Probe adjusted both radially and circumferentially. In addition, pressure-sensing transducer cooled internally by water or other cooling fluid passing through annulus of cooling system.

  7. Evolutionary analysis of TLR9 genes reveals the positive selection of extant teleosts in Perciformes.

    PubMed

    Zhu, Zhihuang; Sun, Yuena; Wang, Rixin; Xu, Tianjun

    2013-08-01

    The innate immune system can recognize non-self through pattern recognition receptors. Toll-like receptors were the best-known members of these receptors, and they could sense, recognize, and bind pathogen-associated molecular patterns. TLRs played an important role in innate immune system and were conserved in both invertebrate and vertebrate lineages. Thereinto, TLR9 could detect unmethylated CpG motifs in dsDNA and was expected to undergo coevolution with its microbial ligands. It was known that aquatic and terrestrial organisms dwelled in different environments which contained different pathogens, and they had to adapt to their local environmental conditions. Therefore, we collected TLR9 genes from invertebrate to vertebrate to further explore whether the huge differences between aquatic and terrestrial environments affected the TLR9s evolution between aquatic and terrestrial organisms. Molecular evolution analysis detected positively selected sites in the ancestral lineages of vertebrates, teleosts, and Perciformes but not in the ancestral lineage of mammals. In PAML, site model revealed that extant mammalian TLR9 genes underwent positive selection. However, the positive selection of extant teleosts appeared primarily in Perciformes in which there were 14 positively selected sites. Among these sites, two of them were located on the amino acid insertions of the leucine-rich repeats which could create DNA binding sites, three were found on the convex surface which might possibly affect the flexibility of the TLR solenoids, and six were located on the β-face of concave surface which contained the ligand-binding sites of the TLR solenoids. In other ML methods, we also found three sites under selection that coincided with the codons identified by M8 and these sites were all located in LRRs. The diverse aquatic and terrestrial environments might possess different pathogens to make the living organisms adapt to their local environmental conditions. The positive

  8. CERAMIC: Case-Control Association Testing in Samples with Related Individuals, Based on Retrospective Mixed Model Analysis with Adjustment for Covariates

    PubMed Central

    Zhong, Sheng; McPeek, Mary Sara

    2016-01-01

    We consider the problem of genetic association testing of a binary trait in a sample that contains related individuals, where we adjust for relevant covariates and allow for missing data. We propose CERAMIC, an estimating equation approach that can be viewed as a hybrid of logistic regression and linear mixed-effects model (LMM) approaches. CERAMIC extends the recently proposed CARAT method to allow samples with related individuals and to incorporate partially missing data. In simulations, we show that CERAMIC outperforms existing LMM and generalized LMM approaches, maintaining high power and correct type 1 error across a wider range of scenarios. CERAMIC results in a particularly large power increase over existing methods when the sample includes related individuals with some missing data (e.g., when some individuals with phenotype and covariate information have missing genotype), because CERAMIC is able to make use of the relationship information to incorporate partially missing data in the analysis while correcting for dependence. Because CERAMIC is based on a retrospective analysis, it is robust to misspecification of the phenotype model, resulting in better control of type 1 error and higher power than that of prospective methods, such as GMMAT, when the phenotype model is misspecified. CERAMIC is computationally efficient for genomewide analysis in samples of related individuals of almost any configuration, including small families, unrelated individuals and even large, complex pedigrees. We apply CERAMIC to data on type 2 diabetes (T2D) from the Framingham Heart Study. In a genome scan, 9 of the 10 smallest CERAMIC p-values occur in or near either known T2D susceptibility loci or plausible candidates, verifying that CERAMIC is able to home in on the important loci in a genome scan. PMID:27695091

  9. Weighted triangulation adjustment

    USGS Publications Warehouse

    Anderson, Walter L.

    1969-01-01

    The variation of coordinates method is employed to perform a weighted least squares adjustment of horizontal survey networks. Geodetic coordinates are required for each fixed and adjustable station. A preliminary inverse geodetic position computation is made for each observed line. Weights associated with each observed equation for direction, azimuth, and distance are applied in the formation of the normal equations in-the least squares adjustment. The number of normal equations that may be solved is twice the number of new stations and less than 150. When the normal equations are solved, shifts are produced at adjustable stations. Previously computed correction factors are applied to the shifts and a most probable geodetic position is found for each adjustable station. Pinal azimuths and distances are computed. These may be written onto magnetic tape for subsequent computation of state plane or grid coordinates. Input consists of punch cards containing project identification, program options, and position and observation information. Results listed include preliminary and final positions, residuals, observation equations, solution of the normal equations showing magnitudes of shifts, and a plot of each adjusted and fixed station. During processing, data sets containing irrecoverable errors are rejected and the type of error is listed. The computer resumes processing of additional data sets.. Other conditions cause warning-errors to be issued, and processing continues with the current data set.

  10. Scenario analysis of carbon emissions' anti-driving effect on Qingdao's energy structure adjustment with an optimization model, Part II: Energy system planning and management.

    PubMed

    Wu, C B; Huang, G H; Liu, Z P; Zhen, J L; Yin, J G

    2017-03-01

    In this study, an inexact multistage stochastic mixed-integer programming (IMSMP) method was developed for supporting regional-scale energy system planning (EPS) associated with multiple uncertainties presented as discrete intervals, probability distributions and their combinations. An IMSMP-based energy system planning (IMSMP-ESP) model was formulated for Qingdao to demonstrate its applicability. Solutions which can provide optimal patterns of energy resources generation, conversion, transmission, allocation and facility capacity expansion schemes have been obtained. The results can help local decision makers generate cost-effective energy system management schemes and gain a comprehensive tradeoff between economic objectives and environmental requirements. Moreover, taking the CO2 emissions scenarios mentioned in Part I into consideration, the anti-driving effect of carbon emissions on energy structure adjustment was studied based on the developed model and scenario analysis. Several suggestions can be concluded from the results: (a) to ensure the smooth realization of low-carbon and sustainable development, appropriate price control and fiscal subsidy on high-cost energy resources should be considered by the decision-makers; (b) compared with coal, natural gas utilization should be strongly encouraged in order to insure that Qingdao could reach the carbon discharges peak value in 2020; (c) to guarantee Qingdao's power supply security in the future, the construction of new power plants should be emphasised instead of enhancing the transmi