From Genome to Function: Systematic Analysis of the Soil Bacterium Bacillus Subtilis

PubMed Central

Crawshaw, Samuel G.; Wipat, Anil

2001-01-01

Bacillus subtilis is a sporulating Gram-positive bacterium that lives primarily in the soil and associated water sources. Whilst this bacterium has been studied extensively in the laboratory, relatively few studies have been undertaken to study its activity in natural environments. The publication of the B. subtilis genome sequence and subsequent systematic functional analysis programme have provided an opportunity to develop tools for analysing the role and expression of Bacillus genes in situ. In this paper we discuss analytical approaches that are being developed to relate genes to function in environments such as the rhizosphere. PMID:18628943

Detection of Functional Change Using Cluster Trend Analysis in Glaucoma.

PubMed

Gardiner, Stuart K; Mansberger, Steven L; Demirel, Shaban

2017-05-01

Global analyses using mean deviation (MD) assess visual field progression, but can miss localized changes. Pointwise analyses are more sensitive to localized progression, but more variable so require confirmation. This study assessed whether cluster trend analysis, averaging information across subsets of locations, could improve progression detection. A total of 133 test-retest eyes were tested 7 to 10 times. Rates of change and P values were calculated for possible re-orderings of these series to generate global analysis ("MD worsening faster than x dB/y with P < y"), pointwise and cluster analyses ("n locations [or clusters] worsening faster than x dB/y with P < y") with specificity exactly 95%. These criteria were applied to 505 eyes tested over a mean of 10.5 years, to find how soon each detected "deterioration," and compared using survival models. This was repeated including two subsequent visual fields to determine whether "deterioration" was confirmed. The best global criterion detected deterioration in 25% of eyes in 5.0 years (95% confidence interval [CI], 4.7-5.3 years), compared with 4.8 years (95% CI, 4.2-5.1) for the best cluster analysis criterion, and 4.1 years (95% CI, 4.0-4.5) for the best pointwise criterion. However, for pointwise analysis, only 38% of these changes were confirmed, compared with 61% for clusters and 76% for MD. The time until 25% of eyes showed subsequently confirmed deterioration was 6.3 years (95% CI, 6.0-7.2) for global, 6.3 years (95% CI, 6.0-7.0) for pointwise, and 6.0 years (95% CI, 5.3-6.6) for cluster analyses. Although the specificity is still suboptimal, cluster trend analysis detects subsequently confirmed deterioration sooner than either global or pointwise analyses.

Multi-voxel patterns of visual category representation during episodic encoding are predictive of subsequent memory

PubMed Central

Kuhl, Brice A.; Rissman, Jesse; Wagner, Anthony D.

2012-01-01

Successful encoding of episodic memories is thought to depend on contributions from prefrontal and temporal lobe structures. Neural processes that contribute to successful encoding have been extensively explored through univariate analyses of neuroimaging data that compare mean activity levels elicited during the encoding of events that are subsequently remembered vs. those subsequently forgotten. Here, we applied pattern classification to fMRI data to assess the degree to which distributed patterns of activity within prefrontal and temporal lobe structures elicited during the encoding of word-image pairs were diagnostic of the visual category (Face or Scene) of the encoded image. We then assessed whether representation of category information was predictive of subsequent memory. Classification analyses indicated that temporal lobe structures contained information robustly diagnostic of visual category. Information in prefrontal cortex was less diagnostic of visual category, but was nonetheless associated with highly reliable classifier-based evidence for category representation. Critically, trials associated with greater classifier-based estimates of category representation in temporal and prefrontal regions were associated with a higher probability of subsequent remembering. Finally, consideration of trial-by-trial variance in classifier-based measures of category representation revealed positive correlations between prefrontal and temporal lobe representations, with the strength of these correlations varying as a function of the category of image being encoded. Together, these results indicate that multi-voxel representations of encoded information can provide unique insights into how visual experiences are transformed into episodic memories. PMID:21925190

Obesity and Functioning Among Individuals with Chronic Obstructive Pulmonary Disease (COPD).

PubMed

Katz, Patricia; Iribarren, Carlos; Sanchez, Gabriela; Blanc, Paul D

2016-06-01

In COPD, body composition studies have focused primarily on low BMI. We examined obesity (BMI ≥ 30 kg/m(2)) as a risk factor for poor function and longitudinal functional decline. Data from a longitudinal cohort of adults with COPD (n = 1096) and an age- and sex-matched comparison group collected in two in-person visits ∼49 months apart were analyzed. Two measures of functioning were examined: six-minute walk distance (6MWD) and Short Physical Performance Battery (SPPB). Multivariate regression analyses examined relationships of obesity with functioning. Secondary analyses stratified by GOLD classification (GOLD-0/1, GOLD-2, GOLD-3/4). Obesity (53% of COPD cohort) was associated cross-sectionally with 6MWD and SPPB in COPD, and only with 6MWD in the comparison group. Obesity predicted significant functional decline in 6MWD for individuals with COPD (odds ratio (OR) for decline [95% CI] 1.8 [1.1, 2.9]), but not the comparison group. Secondary analyses revealed that the risk of decline was significant only in those with more severe COPD (GOLD 3/4, OR = 2.3 [1.0, 5.4]). Obesity was highly prevalent and was associated with poor function concurrently and with subsequent decline in 6MWD in COPD. Obesity in COPD should be considered a risk not only for more co-morbidities and greater health care use, but also for functional decline.

Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function

PubMed Central

Luo, Xiong-Jian; Mattheisen, Manuel; Li, Ming; Huang, Liang; Rietschel, Marcella; Børglum, Anders D.; Als, Thomas D.; van den Oord, Edwin J.; Aberg, Karolina A.; Mors, Ole; Mortensen, Preben Bo; Luo, Zhenwu; Degenhardt, Franziska; Cichon, Sven; Schulze, Thomas G.; Nöthen, Markus M.; Su, Bing; Zhao, Zhongming; Gan, Lin; Yao, Yong-Gang

2015-01-01

Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22×10–6). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40×10–6; single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: P = 6.85×10−10). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62×10–5 and P = 9.00×10–5, respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function. Subsequent population genetics analyses suggest that the risk allele (T) of rs1150711 might have undergone recent positive selection in human population. Our findings suggest that the ZNF323 is a schizophrenia susceptibility gene whose expression may influence schizophrenia risk. Our study also illustrates a possible mechanism for maintaining schizophrenia risk variants in the human gene pool. PMID:25759474

40 CFR 63.7515 - When must I conduct subsequent performance tests, fuel analyses, or tune-ups?

Code of Federal Regulations, 2011 CFR

2011-07-01

... performance tests, fuel analyses, or tune-ups? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL... Compliance Requirements § 63.7515 When must I conduct subsequent performance tests, fuel analyses, or tune... and the associated initial fuel analyses within 90 days after the completion of the performance tests...

40 CFR 63.7515 - When must I conduct subsequent performance tests, fuel analyses, or tune-ups?

Code of Federal Regulations, 2012 CFR

2012-07-01

... performance tests, fuel analyses, or tune-ups? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL... Compliance Requirements § 63.7515 When must I conduct subsequent performance tests, fuel analyses, or tune... and the associated initial fuel analyses within 90 days after the completion of the performance tests...

Analysis of functional redundancies within the Arabidopsis TCP transcription factor family.

PubMed

Danisman, Selahattin; van Dijk, Aalt D J; Bimbo, Andrea; van der Wal, Froukje; Hennig, Lars; de Folter, Stefan; Angenent, Gerco C; Immink, Richard G H

2013-12-01

Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein-protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein-protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family.

Analysis of functional redundancies within the Arabidopsis TCP transcription factor family

PubMed Central

Danisman, Selahattin; de Folter, Stefan; Immink, Richard G. H.

2013-01-01

Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein–protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein–protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family. PMID:24129704

Attachment comes of age: adolescents' narrative coherence and reflective functioning predict well-being in emerging adulthood.

PubMed

Borelli, Jessica L; Brugnera, Agostino; Zarbo, Cristina; Rabboni, Massimo; Bondi, Emi; Tasca, Giorgio A; Compare, Angelo

2018-06-04

This study investigated the effects of adolescents' attachment security and reflective functioning (RF) (assessed by the adult attachment interview [AAI]) in the prediction of well-being in adulthood. Adolescents (N = 79; M = 14.6 years old; SD = 3.5 years) completed the AAI at Time 1 (T1), which was subsequently coded for inferred attachment experiences, narrative coherence, and RF by three nonoverlapping teams of raters. Participants completed the Psychological General Well-being Index at T1 and 8 years later (Time 2, T2). Analyses showed that (a) both adolescent narrative coherence and RF were significant predictors of almost all indices of well-being at T2 in adulthood; (b) both narrative coherence and RF indirectly linked inferred loving parental care and T2 well-being; (c) when included in the same model, RF was a significant indirect effect linking inferred loving parental care and T2 well-being. These findings contribute to theory in suggesting that both RF and narrative coherence are predictive of subsequent psychological well-being and operate as links between inferred parental care and subsequent adjustment. Possible mechanisms underlying these findings are discussed.

Digital fabrication of multi-material biomedical objects.

PubMed

Cheung, H H; Choi, S H

2009-12-01

This paper describes a multi-material virtual prototyping (MMVP) system for modelling and digital fabrication of discrete and functionally graded multi-material objects for biomedical applications. The MMVP system consists of a DMMVP module, an FGMVP module and a virtual reality (VR) simulation module. The DMMVP module is used to model discrete multi-material (DMM) objects, while the FGMVP module is for functionally graded multi-material (FGM) objects. The VR simulation module integrates these two modules to perform digital fabrication of multi-material objects, which can be subsequently visualized and analysed in a virtual environment to optimize MMLM processes for fabrication of product prototypes. Using the MMVP system, two biomedical objects, including a DMM human spine and an FGM intervertebral disc spacer are modelled and digitally fabricated for visualization and analysis in a VR environment. These studies show that the MMVP system is a practical tool for modelling, visualization, and subsequent fabrication of biomedical objects of discrete and functionally graded multi-materials for biomedical applications. The system may be adapted to control MMLM machines with appropriate hardware for physical fabrication of biomedical objects.

Classroom-based functional and adjunctive assessments: proactive approaches to intervention selection for adolescents with attention deficit hyperactivity disorder.

PubMed Central

Ervin, R A; DuPaul, G J; Kern, L; Friman, P C

1998-01-01

The present investigation evaluated the utility of classroom-based functional and adjunctive assessments of problem behaviors for 2 adolescents who met diagnostic criteria for attention deficit hyperactivity disorder (ADHD) and comorbid oppositional defiant disorder (ODD). For children with ADHD-ODD, environmental classroom variables, when systematically manipulated by teachers, were related to the occurrence and nonoccurrence of problem behaviors. Classroom interventions derived from information that was obtained during functional and adjunctive assessments and from subsequent analyses resulted in substantial reductions in problem behaviors. Teacher and student consumer satisfaction ratings indicated that the interventions were effective and feasible in the classroom setting. PMID:9532751

SAS2H Generated Isotopic Concentrations For B&W 15X15 PWR Assembly (SCPB:N/A)

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

J.W. Davis

This analysis is prepared by the Mined Geologic Disposal System (MGDS) Waste Package Development Department (WPDD) to provide pressurized water reactor (PWR) isotopic composition data as a function of time for use in criticality analyses. The objectives of this evaluation are to generate burnup and decay dependant isotopic inventories and to provide these inventories in a form which can easily be utilized in subsequent criticality calculations.

40 CFR 63.7515 - When must I conduct subsequent performance tests or fuel analyses?

Code of Federal Regulations, 2010 CFR

2010-07-01

... performance tests or fuel analyses? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL PROTECTION... Requirements § 63.7515 When must I conduct subsequent performance tests or fuel analyses? (a) You must conduct... previous performance test. (f) You must conduct a fuel analysis according to § 63.7521 for each type of...

40 CFR 63.11220 - When must I conduct subsequent performance tests or fuel analyses?

Code of Federal Regulations, 2014 CFR

2014-07-01

... performance tests or fuel analyses? 63.11220 Section 63.11220 Protection of Environment ENVIRONMENTAL... When must I conduct subsequent performance tests or fuel analyses? (a) If your boiler has a heat input... performance (stack) tests according to § 63.11212 on a triennial basis, except as specified in paragraphs (b...

40 CFR 63.7515 - When must I conduct subsequent performance tests or fuel analyses?

Code of Federal Regulations, 2011 CFR

2011-07-01

... performance tests or fuel analyses? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL PROTECTION... Requirements § 63.7515 When must I conduct subsequent performance tests or fuel analyses? (a) You must conduct... previous performance test. (f) You must conduct a fuel analysis according to § 63.7521 for each type of...

40 CFR 63.11220 - When must I conduct subsequent performance tests or fuel analyses?

Code of Federal Regulations, 2013 CFR

2013-07-01

... performance tests or fuel analyses? 63.11220 Section 63.11220 Protection of Environment ENVIRONMENTAL... When must I conduct subsequent performance tests or fuel analyses? (a) If your boiler has a heat input... performance (stack) tests according to § 63.11212 on a triennial basis, except as specified in paragraphs (b...

40 CFR 63.7515 - When must I conduct subsequent performance tests or fuel analyses?

Code of Federal Regulations, 2012 CFR

2012-07-01

... performance tests or fuel analyses? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL PROTECTION... Requirements § 63.7515 When must I conduct subsequent performance tests or fuel analyses? (a) You must conduct... previous performance test. (f) You must conduct a fuel analysis according to § 63.7521 for each type of...

Functional and conformational properties of phaseolin (Phaseolus vulgris L.) and kidney bean protein isolate: a comparative study.

PubMed

Yin, Shou-Wei; Tang, Chuan-He; Wen, Qi-Biao; Yang, Xiao-Quan

2010-03-15

Kidney bean (Phaseolus vulgris L.) seed is an underutilised plant protein source with good potential to be applied in the food industry. Phaseolin (also named G1 globulin) represents about 50 g kg(-1) of total storage protein in the seed. The aim of the present study was to characterise physicochemical, functional and conformational properties of phaseolin, and to compare these properties with those of kidney bean protein isolate (KPI). Compared with kidney bean protein isolate (KPI), the acid-extracted phaseolin-rich protein product (PRP) had much lower protein recovery of 320 g kg(-1) (dry weight basis) but higher phaseolin purity (over 950 g kg(-1)). PRP contained much lower sulfhydryl (SH) and disulfide bond contents than KPI. Differential scanning calorimetry analyses showed that the phaseolin in PRP was less denatured than in KPI. Thermal analyses in the presence or absence of dithiothreitol, in combination with SH and SS content analyses showed the contributions of SS to the thermal stability of KPI. The analyses of near-UV circular dichroism and intrinsic fluorescence spectra indicated more compacted tertiary conformation of the proteins in PRP than in KPI. PRP exhibited much better protein solubility, emulsifying activity index, and gel-forming ability than KPI. The relatively poor functional properties of KPI may be associated with protein denaturation/unfolding, with subsequent protein aggregation. The results presented here suggest the potential for acid-extracted PRP to be applied in food formulations, in view of its functional properties.

Parent-child interaction over time in families of young children with borderline intellectual functioning.

PubMed

Fenning, Rachel M; Baker, Jason K; Baker, Bruce L; Crnic, Keith A

2014-06-01

A previous study suggested that mothers of 5-year-old children with borderline intellectual functioning displayed lower positive engagement with their children as compared with both mothers of typically developing children and mothers of children with significant developmental delays (Fenning, Baker, Baker, & Crnic, 2007). The current study integrated father data and followed these families over the subsequent 1-year period. Parent and child behavior were coded from naturalistic home observations at both waves. Results revealed that mothers of children with borderline intellectual functioning displayed a greater increase in negative-controlling parenting from child age 5 to 6 than did other mothers; fathers displayed more negative-controlling behavior in comparison to fathers of typically developing children. In addition, children with borderline intellectual functioning themselves exhibited a more significant escalation in difficult behavior than did typically developing children. Cross-lagged analyses for the sample as a whole indicated that maternal negative-controlling behavior predicted subsequent child difficulties, whereas negative paternal behavior was predicted by earlier child behavior. In conjunction with evidence from Fenning et al. (2007), these findings suggest a complex, dynamic, and systemic developmental pattern in the emotional behavior of families of children with borderline intellectual functioning. Implications and areas in need of additional research are discussed. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Bidirectional Relationship between Cognitive Function and Pneumonia

PubMed Central

Shah, Faraaz Ali; Pike, Francis; Alvarez, Karina; Angus, Derek; Newman, Anne B.; Lopez, Oscar; Tate, Judith; Kapur, Vishesh; Wilsdon, Anthony; Krishnan, Jerry A.; Hansel, Nadia; Au, David; Avdalovic, Mark; Fan, Vincent S.; Barr, R. Graham

2013-01-01

Rationale: Relationships between chronic health conditions and acute infections remain poorly understood. Preclinical studies suggest crosstalk between nervous and immune systems. Objectives: To determine bidirectional relationships between cognition and pneumonia. Methods: We conducted longitudinal analyses of a population-based cohort over 10 years. We determined whether changes in cognition increase risk of pneumonia hospitalization by trajectory analyses and joint modeling. We then determined whether pneumonia hospitalization increased risk of subsequent dementia using a Cox model with pneumonia as a time-varying covariate. Measurements and Main Results: Of the 5,888 participants, 639 (10.9%) were hospitalized with pneumonia at least once. Most participants had normal cognition before pneumonia. Three cognition trajectories were identified: no, minimal, and severe rapid decline. A greater proportion of participants hospitalized with pneumonia were on trajectories of minimal or severe decline before occurrence of pneumonia compared with those never hospitalized with pneumonia (proportion with no, minimal, and severe decline were 67.1%, 22.8%, and 10.0% vs. 76.0%, 19.3%, and 4.6% for participants with and without pneumonia, respectively; P < 0.001). Small subclinical changes in cognition increased risk of pneumonia, even in those with normal cognition and physical function before pneumonia (β = −0.02; P < 0.001). Participants with pneumonia were subsequently at an increased risk of dementia (hazard ratio, 2.24 [95% confidence interval, 1.62–3.11]; P = 0.01). Associations were independent of demographics, health behaviors, other chronic conditions, and physical function. Bidirectional relationship did not vary based on severity of disease, and similar associations were noted for those with severe sepsis and other infections. Conclusions: A bidirectional relationship exists between pneumonia and cognition and may explain how a single episode of infection in well-appearing older individuals accelerates decline in chronic health conditions and loss of functional independence. PMID:23848267

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

PubMed Central

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

2009-01-01

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

Progressing from programmatic to discovery research: a case example with the overjustification effect.

PubMed

Roane, Henry S; Fisher, Wayne W; McDonough, Erin M

2003-01-01

Scientific research progresses along planned (programmatic research) and unplanned (discovery research) paths. In the current investigation, we attempted to conduct a single-case evaluation of the overjustification effect (i.e., programmatic research). Results of the initial analysis were contrary to the overjustification hypothesis in that removal of the reward contingency produced an increase in responding. Based on this unexpected finding, we conducted subsequent analyses to further evaluate the mechanisms underlying these results (i.e., discovery research). Results of the additional analyses suggested that the reward contingency functioned as punishment (because the participant preferred the task to the rewards) and that withdrawal of the contingency produced punishment contrast.

Progressing from programmatic to discovery research: a case example with the overjustification effect.

PubMed Central

Roane, Henry S; Fisher, Wayne W; McDonough, Erin M

2003-01-01

Scientific research progresses along planned (programmatic research) and unplanned (discovery research) paths. In the current investigation, we attempted to conduct a single-case evaluation of the overjustification effect (i.e., programmatic research). Results of the initial analysis were contrary to the overjustification hypothesis in that removal of the reward contingency produced an increase in responding. Based on this unexpected finding, we conducted subsequent analyses to further evaluate the mechanisms underlying these results (i.e., discovery research). Results of the additional analyses suggested that the reward contingency functioned as punishment (because the participant preferred the task to the rewards) and that withdrawal of the contingency produced punishment contrast. PMID:12723865

Relationships Between Sleep Quality and Pain-Related Factors for People with Chronic Low Back Pain: Tests of Reciprocal and Time of Day Effects.

PubMed

Gerhart, James I; Burns, John W; Post, Kristina M; Smith, David A; Porter, Laura S; Burgess, Helen J; Schuster, Erik; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J

2017-06-01

Poor sleep quality among people with chronic low back pain appears to be related to worse pain, affect, poor physical function, and pain catastrophizing. The causal direction between poor sleep and pain remains an open question, however, as does whether sleep quality exerts effects on low back pain differently across the course of the day. This daily diary study examined lagged temporal associations between prior night sleep quality and subsequent day pain, affect, physical function and pain catastrophizing, the reverse lagged temporal associations between prior day pain-related factors and subsequent night sleep quality, and whether the time of day during which an assessment was made moderated these temporal associations. Chronic low back pain patients (n = 105) completed structured electronic diary assessments five times per day for 14 days. Items included patient ratings of their pain, affect, physical function, and pain catastrophizing. Collapsed across all observations, poorer sleep quality was significantly related to higher pain ratings, higher negative affect, lower positive affect, poorer physical function, and higher pain catastrophizing. Lagged analyses averaged across the day revealed that poorer prior night sleep quality significantly predicted greater next day patient ratings of pain, and poorer physical function and higher pain catastrophizing. Prior poorer night sleep quality significantly predicted greater reports of pain, and poorer physical function, and higher pain catastrophizing, especially during the early part of the day. Sleep quality × time of day interactions showed that poor sleepers reported high pain, and negative mood and low function uniformly across the day, whereas good sleepers reported relatively good mornings, but showed pain, affect and function levels comparable to poor sleepers by the end of the day. Analyses of the reverse causal pathway were mostly nonsignificant. Sleep quality appears related not only to pain intensity but also to a wide range of patient mood and function factors. A good night's sleep also appears to offer only temporary respite, suggesting that comprehensive interventions for chronic low back pain not only should include attention to sleep problems but also focus on problems with pain appraisals and coping.

Relationships Between Sleep Quality and Pain-Related Factors for People with Chronic Low Back Pain: Tests of Reciprocal and Time of Day Effects

PubMed Central

Gerhart, James I.; Burns, John W.; Post, Kristina M.; Smith, David A.; Porter, Laura S.; Burgess, Helen J.; Schuster, Erik; Buvanendran, Asokumar; Fras, Anne Marie; Keefe, Francis J.

2016-01-01

Background Poor sleep quality among people with chronic low back pain appears to be related to worse pain, affect, poor physical function and pain catastrophizing. The causal direction between poor sleep and pain remains an open question, however, as does whether sleep quality exerts effects on low back pain differently across the course of the day. Purpose This daily diary study examined lagged temporal associations between prior night sleep quality and subsequent day pain, affect, physical function and pain catastrophizing, the reverse lagged temporal associations between prior day pain-related factors and subsequent night sleep quality, and whether the time of day during which an assessment was made moderated these temporal associations. Methods Chronic low back pain patients (n = 105) completed structured electronic diary assessments five times per day for 14 days. Items included patient ratings of their pain, affect, physical function and pain catastrophizing. Results Collapsed across all observations, poorer sleep quality was significantly related to higher pain ratings, higher negative affect, lower positive affect, poorer physical function and higher pain catastrophizing. Lagged analyses averaged across the day revealed that poorer prior night sleep quality significantly predicted greater next day patient ratings of pain, and poorer physical function and higher pain catastrophizing. Prior poorer night sleep quality significantly predicted greater reports of pain, and poorer physical function, and higher pain catastrophizing, especially during the early part of the day. Sleep Quality × Time of Day interactions showed that poor sleepers reported high pain, and negative mood and low function uniformly across the day, whereas good sleepers reported relatively good mornings, but showed pain, affect and function levels comparable to poor sleepers by the end of the day. Analyses of the reverse causal pathway were mostly nonsignificant. Conclusions Sleep quality appears related not only to pain intensity but also to a wide range of patient mood and function factors. A good night’s sleep also appears to offer only temporary respite, suggesting that comprehensive interventions for chronic low back pain not only should include attention to sleep problems but also focus on problems with pain appraisals and coping. PMID:27844327

Disorganized Symptoms Predicted Worse Functioning Outcome in Schizophrenia Patients with Established Illness.

PubMed

Ortiz, Bruno Bertolucci; Gadelha, Ary; Higuchi, Cinthia Hiroko; Noto, Cristiano; Medeiros, Daiane; Pitta, José Cássio do Nascimento; de Araújo Filho, Gerardo Maria; Hallak, Jaime Eduardo Cecílio; Bressan, Rodrigo Affonseca

Most patients with schizophrenia will have subsequent relapses of the disorder, with continuous impairments in functioning. However, evidence is lacking on how symptoms influence functioning at different phases of the disease. This study aims to investigate the relationship between symptom dimensions and functioning at different phases: acute exacerbation, nonremission and remission. Patients with schizophrenia were grouped into acutely ill (n=89), not remitted (n=89), and remitted (n=69). Three exploratory stepwise linear regression analyses were performed for each phase of schizophrenia, in which the five PANSS factors and demographic variables were entered as the independent variables and the total Global Assessment of Functioning Scale (GAF) score was entered as the dependent variable. An additional exploratory stepwise logistic regression analysis was performed to predict subsequent remission at discharge in the inpatient population. The Disorganized factor was the most significant predictor for acutely ill patients (p<0.001), while the Hostility factor was the most significant for not-remitted patients and the Negative factor was the most significant for remitted patients (p=0.001 and p<0.001, respectively). In the logistic regression, the Disorganized factor score presented a significant negative association with remission (p=0.007). Higher disorganization symptoms showed the greatest impact in functioning at acute phase, and prevented patients from achieving remission, suggesting it may be a marker of symptom severity and worse outcome in schizophrenia.

Comparative functional analyses of ultrabithorax reveal multiple steps and paths to diversification of legs in the adaptive radiation of semi-aquatic insects.

PubMed

Khila, Abderrahman; Abouheif, Ehab; Rowe, Locke

2014-08-01

Invasion of new ecological habitats is often associated with lineage diversification, yet the genetic changes underlying invasions and radiations are poorly understood. Over 200 million years ago, the semi-aquatic insects invaded water surface from a common terrestrial ancestor and diversified to exploit a wide array of niches. Here, we uncover the changes in regulation and function of the gene Ultrabithorax associated with both the invasion of water surface and the subsequent diversification of the group. In the common ancestor of the semi-aquatic insects, a novel deployment of Ubx protein in the mid-legs increased their length, thereby enhancing their role in water surface walking. In derived lineages that specialize in rowing on the open water, additional changes in the timing of Ubx expression further elongated the mid-legs thereby facilitating their function as oars. In addition, Ubx protein function was selectively reversed to shorten specific rear-leg segments, thereby enabling their function as rudders. These changes in Ubx have generated distinct niche-specialized morphologies that account for the remarkable diversification of the semi-aquatic insects. Therefore, changes in the regulation and function of a key developmental gene may facilitate both the morphological change necessary to transition to novel habitats and fuel subsequent morphological diversification. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

Automatically visualise and analyse data on pathways using PathVisioRPC from any programming environment.

PubMed

Bohler, Anwesha; Eijssen, Lars M T; van Iersel, Martijn P; Leemans, Christ; Willighagen, Egon L; Kutmon, Martina; Jaillard, Magali; Evelo, Chris T

2015-08-23

Biological pathways are descriptive diagrams of biological processes widely used for functional analysis of differentially expressed genes or proteins. Primary data analysis, such as quality control, normalisation, and statistical analysis, is often performed in scripting languages like R, Perl, and Python. Subsequent pathway analysis is usually performed using dedicated external applications. Workflows involving manual use of multiple environments are time consuming and error prone. Therefore, tools are needed that enable pathway analysis directly within the same scripting languages used for primary data analyses. Existing tools have limited capability in terms of available pathway content, pathway editing and visualisation options, and export file formats. Consequently, making the full-fledged pathway analysis tool PathVisio available from various scripting languages will benefit researchers. We developed PathVisioRPC, an XMLRPC interface for the pathway analysis software PathVisio. PathVisioRPC enables creating and editing biological pathways, visualising data on pathways, performing pathway statistics, and exporting results in several image formats in multiple programming environments. We demonstrate PathVisioRPC functionalities using examples in Python. Subsequently, we analyse a publicly available NCBI GEO gene expression dataset studying tumour bearing mice treated with cyclophosphamide in R. The R scripts demonstrate how calls to existing R packages for data processing and calls to PathVisioRPC can directly work together. To further support R users, we have created RPathVisio simplifying the use of PathVisioRPC in this environment. We have also created a pathway module for the microarray data analysis portal ArrayAnalysis.org that calls the PathVisioRPC interface to perform pathway analysis. This module allows users to use PathVisio functionality online without having to download and install the software and exemplifies how the PathVisioRPC interface can be used by data analysis pipelines for functional analysis of processed genomics data. PathVisioRPC enables data visualisation and pathway analysis directly from within various analytical environments used for preliminary analyses. It supports the use of existing pathways from WikiPathways or pathways created using the RPC itself. It also enables automation of tasks performed using PathVisio, making it useful to PathVisio users performing repeated visualisation and analysis tasks. PathVisioRPC is freely available for academic and commercial use at http://projects.bigcat.unimaas.nl/pathvisiorpc.

Flow cytometric sorting of fecal bacteria after in situ hybridization with polynucleotide probes.

PubMed

Bruder, Lena M; Dörkes, Marcel; Fuchs, Bernhard M; Ludwig, Wolfgang; Liebl, Wolfgang

2016-10-01

The gut microbiome represents a key contributor to human physiology, metabolism, immune function, and nutrition. Elucidating the composition and genetics of the gut microbiota under various conditions is essential to understand how microbes function individually and as a community. Metagenomic analyses are increasingly used to study intestinal microbiota. However, for certain scientific questions it is sufficient to examine taxon-specific submetagenomes, covering selected bacterial genera in a targeted manner. Here we established a new variant of fluorescence in situ hybridization (FISH) combined with fluorescence-activated cell sorting (FACS), providing access to the genomes of specific taxa belonging to the complex community of the intestinal microbiota. In contrast to standard oligonucleotide probes, the RNA polynucleotide probe used here, which targets domain III of the 23S rRNA gene, extends the resolution power in environmental samples by increasing signal intensity. Furthermore, cells hybridized with the polynucleotide probe are not subjected to harsh pretreatments, and their genetic information remains intact. The protocol described here was tested on genus-specifically labeled cells in various samples, including complex fecal samples from different laboratory mouse types that harbor diverse intestinal microbiota. Specifically, as an example for the protocol described here, RNA polynucleotide probes could be used to label Enterococcus cells for subsequent sorting by flow cytometry. To detect and quantify enterococci in fecal samples prior to enrichment, taxon-specific PCR and qPCR detection systems have been developed. The accessibility of the genomes from taxon-specifically sorted cells for subsequent molecular analyses was demonstrated by amplification of functional genes. Copyright © 2016 Elsevier GmbH. All rights reserved.

Systematic Integration of Brain eQTL and GWAS Identifies ZNF323 as a Novel Schizophrenia Risk Gene and Suggests Recent Positive Selection Based on Compensatory Advantage on Pulmonary Function.

PubMed

Luo, Xiong-Jian; Mattheisen, Manuel; Li, Ming; Huang, Liang; Rietschel, Marcella; Børglum, Anders D; Als, Thomas D; van den Oord, Edwin J; Aberg, Karolina A; Mors, Ole; Mortensen, Preben Bo; Luo, Zhenwu; Degenhardt, Franziska; Cichon, Sven; Schulze, Thomas G; Nöthen, Markus M; Su, Bing; Zhao, Zhongming; Gan, Lin; Yao, Yong-Gang

2015-11-01

Genome-wide association studies have identified multiple risk variants and loci that show robust association with schizophrenia. Nevertheless, it remains unclear how these variants confer risk to schizophrenia. In addition, the driving force that maintains the schizophrenia risk variants in human gene pool is poorly understood. To investigate whether expression-associated genetic variants contribute to schizophrenia susceptibility, we systematically integrated brain expression quantitative trait loci and genome-wide association data of schizophrenia using Sherlock, a Bayesian statistical framework. Our analyses identified ZNF323 as a schizophrenia risk gene (P = 2.22×10(-6)). Subsequent analyses confirmed the association of the ZNF323 and its expression-associated single nucleotide polymorphism rs1150711 in independent samples (gene-expression: P = 1.40×10(-6); single-marker meta-analysis in the combined discovery and replication sample comprising 44123 individuals: P = 6.85×10(-10)). We found that the ZNF323 was significantly downregulated in hippocampus and frontal cortex of schizophrenia patients (P = .0038 and P = .0233, respectively). Evidence for pleiotropic effects was detected (association of rs1150711 with lung function and gene expression of ZNF323 in lung: P = 6.62×10(-5) and P = 9.00×10(-5), respectively) with the risk allele (T allele) for schizophrenia acting as protective allele for lung function. Subsequent population genetics analyses suggest that the risk allele (T) of rs1150711 might have undergone recent positive selection in human population. Our findings suggest that the ZNF323 is a schizophrenia susceptibility gene whose expression may influence schizophrenia risk. Our study also illustrates a possible mechanism for maintaining schizophrenia risk variants in the human gene pool. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Motor programme activating therapy influences adaptive brain functions in multiple sclerosis: clinical and MRI study.

PubMed

Rasova, Kamila; Prochazkova, Marie; Tintera, Jaroslav; Ibrahim, Ibrahim; Zimova, Denisa; Stetkarova, Ivana

2015-03-01

There is still little scientific evidence for the efficacy of neurofacilitation approaches and their possible influence on brain plasticity and adaptability. In this study, the outcome of a new kind of neurofacilitation approach, motor programme activating therapy (MPAT), was evaluated on the basis of a set of clinical functions and with MRI. Eighteen patients were examined four times with standardized clinical tests and diffusion tensor imaging to monitor changes without therapy, immediately after therapy and 1 month after therapy. Moreover, the strength of effective connectivity was analysed before and after therapy. Patients underwent a 1-h session of MPAT twice a week for 2 months. The data were analysed by nonparametric tests of association and were subsequently statistically evaluated. The therapy led to significant improvement in clinical functions, significant increment of fractional anisotropy and significant decrement of mean diffusivity, and decrement of effective connectivity at supplementary motor areas was observed immediately after the therapy. Changes in clinical functions and diffusion tensor images persisted 1 month after completing the programme. No statistically significant changes in clinical functions and no differences in MRI-diffusion tensor images were observed without physiotherapy. Positive immediate and long-term effects of MPAT on clinical and brain functions, as well as brain microstructure, were confirmed.

FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery

PubMed Central

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-01-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2–ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data. PMID:22570408

FusionAnalyser: a new graphical, event-driven tool for fusion rearrangements discovery.

PubMed

Piazza, Rocco; Pirola, Alessandra; Spinelli, Roberta; Valletta, Simona; Redaelli, Sara; Magistroni, Vera; Gambacorti-Passerini, Carlo

2012-09-01

Gene fusions are common driver events in leukaemias and solid tumours; here we present FusionAnalyser, a tool dedicated to the identification of driver fusion rearrangements in human cancer through the analysis of paired-end high-throughput transcriptome sequencing data. We initially tested FusionAnalyser by using a set of in silico randomly generated sequencing data from 20 known human translocations occurring in cancer and subsequently using transcriptome data from three chronic and three acute myeloid leukaemia samples. in all the cases our tool was invariably able to detect the presence of the correct driver fusion event(s) with high specificity. In one of the acute myeloid leukaemia samples, FusionAnalyser identified a novel, cryptic, in-frame ETS2-ERG fusion. A fully event-driven graphical interface and a flexible filtering system allow complex analyses to be run in the absence of any a priori programming or scripting knowledge. Therefore, we propose FusionAnalyser as an efficient and robust graphical tool for the identification of functional rearrangements in the context of high-throughput transcriptome sequencing data.

School belongingness and mental health functioning across the primary-secondary transition in a mainstream sample: multi-group cross-lagged analyses.

PubMed

Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

2014-01-01

The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students' school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students.

Application of a Novel Functional Gene Microarray to Probe the Functional Ecology of Ammonia Oxidation in Nitrifying Activated Sludge

PubMed Central

Short, Michael D.; Abell, Guy C. J.; Bodrossy, Levente; van den Akker, Ben

2013-01-01

We report on the first study trialling a newly-developed, functional gene microarray (FGA) for characterising bacterial and archaeal ammonia oxidisers in activated sludge. Mixed liquor (ML) and media biofilm samples from a full-scale integrated fixed-film activated sludge (IFAS) plant were analysed with the FGA to profile the diversity and relative abundance of ammonia-oxidising archaea and bacteria (AOA and AOB respectively). FGA analyses of AOA and AOB communities revealed ubiquitous distribution of AOA across all samples – an important finding for these newly-discovered and poorly characterised organisms. Results also revealed striking differences in the functional ecology of attached versus suspended communities within the IFAS reactor. Quantitative assessment of AOB and AOA functional gene abundance revealed a dominance of AOB in the ML and approximately equal distribution of AOA and AOB in the media-attached biofilm. Subsequent correlations of functional gene abundance data with key water quality parameters suggested an important functional role for media-attached AOB in particular for IFAS reactor nitrification performance and indicate possible functional redundancy in some IFAS ammonia oxidiser communities. Results from this investigation demonstrate the capacity of the FGA to resolve subtle ecological shifts in key microbial communities in nitrifying activated sludge and indicate its value as a tool for better understanding the linkages between the ecology and performance of these engineered systems. PMID:24155925

School Belongingness and Mental Health Functioning across the Primary-Secondary Transition in a Mainstream Sample: Multi-Group Cross-Lagged Analyses

PubMed Central

Vaz, Sharmila; Falkmer, Marita; Parsons, Richard; Passmore, Anne Elizabeth; Parkin, Timothy; Falkmer, Torbjörn

2014-01-01

The relationship between school belongingness and mental health functioning before and after the primary-secondary school transition has not been previously investigated in students with and without disabilities. This study used a prospective longitudinal design to test the bi-directional relationships between these constructs, by surveying 266 students with and without disabilities and their parents, 6-months before and after the transition to secondary school. Cross-lagged multi-group analyses found student perception of belongingness in the final year of primary school to contribute to change in their mental health functioning a year later. The beneficial longitudinal effects of school belongingness on subsequent mental health functioning were evident in all student subgroups; even after accounting for prior mental health scores and the cross-time stability in mental health functioning and school belongingness scores. Findings of the current study substantiate the role of school contextual influences on early adolescent mental health functioning. They highlight the importance for primary and secondary schools to assess students’ school belongingness and mental health functioning and transfer these records as part of the transition process, so that appropriate scaffolds are in place to support those in need. Longer term longitudinal studies are needed to increase the understanding of the temporal sequencing between school belongingness and mental health functioning of all mainstream students. PMID:24967580

Modulating Tone to Promote Motor Development Using a Neurofacilitation of Developmental Reaction (NFDR) Approach in Children with Neurodevelopmental Delay

PubMed Central

Batra, Vijay; Batra, Meenakshi; Pandey, Ravindra Mohan; Sharma, Vijai Prakash; Agarwal, Girdhar Gopal

2015-01-01

Objective To compare the efficacy of a Neurofacilitation of Developmental Reaction (NFDR) approach with that of a Conventional approach in the modulation of tone in children with neurodevelopmental delay. Methods Experimental control design. A total of 30 spastic children ranging in age from 4 to 7 years with neurodevelopmental delay were included. Baseline evaluations of muscle tone and gross motor functional performance abilities were performed. The children were allocated into two intervention groups of 15 subjects each. In groups A and B, the NFDR and conventional approaches were applied, respectively, for 3 months and were followed by subsequent re-evaluations. Results Between group analyses were performed using independent t test for tone and primitive reflex intensity and a Mann-Whitney U test for gross motor functional ability. For the within-group analyses, paired t tests were used for tone and primitive reflex intensity, and a Wilcoxon signed-rank test was used for gross motor functional ability. Conclusion The NFDR approach/technique prepares the muscle to undergo tonal modulation and thereby enhances motor development and improves the motor functional performance abilities of the children with neurodevelopmental delay. PMID:28239268

Investigating Linguistic Sources of Differential Item Functioning Using Expert Think-Aloud Protocols in Science Achievement Tests

NASA Astrophysics Data System (ADS)

Roth, Wolff-Michael; Oliveri, Maria Elena; Dallie Sandilands, Debra; Lyons-Thomas, Juliette; Ercikan, Kadriye

2013-03-01

Even if national and international assessments are designed to be comparable, subsequent psychometric analyses often reveal differential item functioning (DIF). Central to achieving comparability is to examine the presence of DIF, and if DIF is found, to investigate its sources to ensure differentially functioning items that do not lead to bias. In this study, sources of DIF were examined using think-aloud protocols. The think-aloud protocols of expert reviewers were conducted for comparing the English and French versions of 40 items previously identified as DIF (N = 20) and non-DIF (N = 20). Three highly trained and experienced experts in verifying and accepting/rejecting multi-lingual versions of curriculum and testing materials for government purposes participated in this study. Although there is a considerable amount of agreement in the identification of differentially functioning items, experts do not consistently identify and distinguish DIF and non-DIF items. Our analyses of the think-aloud protocols identified particular linguistic, general pedagogical, content-related, and cognitive factors related to sources of DIF. Implications are provided for the process of arriving at the identification of DIF, prior to the actual administration of tests at national and international levels.

Unconscious analyses of visual scenes based on feature conjunctions.

PubMed

Tachibana, Ryosuke; Noguchi, Yasuki

2015-06-01

To efficiently process a cluttered scene, the visual system analyzes statistical properties or regularities of visual elements embedded in the scene. It is controversial, however, whether those scene analyses could also work for stimuli unconsciously perceived. Here we show that our brain performs the unconscious scene analyses not only using a single featural cue (e.g., orientation) but also based on conjunctions of multiple visual features (e.g., combinations of color and orientation information). Subjects foveally viewed a stimulus array (duration: 50 ms) where 4 types of bars (red-horizontal, red-vertical, green-horizontal, and green-vertical) were intermixed. Although a conscious perception of those bars was inhibited by a subsequent mask stimulus, the brain correctly analyzed the information about color, orientation, and color-orientation conjunctions of those invisible bars. The information of those features was then used for the unconscious configuration analysis (statistical processing) of the central bars, which induced a perceptual bias and illusory feature binding in visible stimuli at peripheral locations. While statistical analyses and feature binding are normally 2 key functions of the visual system to construct coherent percepts of visual scenes, our results show that a high-level analysis combining those 2 functions is correctly performed by unconscious computations in the brain. (c) 2015 APA, all rights reserved).

SLUDGE TREATMENT PROJECT KOP CONCEPTUAL DESIGN CONTROL DECISION REPORT

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

CARRO CA

2010-03-09

This control decision addresses the Knock-Out Pot (KOP) Disposition KOP Processing System (KPS) conceptual design. The KPS functions to (1) retrieve KOP material from canisters, (2) remove particles less than 600 {micro}m in size and low density materials from the KOP material, (3) load the KOP material into Multi-Canister Overpack (MCO) baskets, and (4) stage the MCO baskets for subsequent loading into MCOs. Hazard and accident analyses of the KPS conceptual design have been performed to incorporate safety into the design process. The hazard analysis is documented in PRC-STP-00098, Knock-Out Pot Disposition Project Conceptual Design Hazard Analysis. The accident analysismore » is documented in PRC-STP-CN-N-00167, Knock-Out Pot Disposition Sub-Project Canister Over Lift Accident Analysis. Based on the results of these analyses, and analyses performed in support of MCO transportation and MCO processing and storage activities at the Cold Vacuum Drying Facility (CVDF) and Canister Storage Building (CSB), control decision meetings were held to determine the controls required to protect onsite and offsite receptors and facility workers. At the conceptual design stage, these controls are primarily defined by their safety functions. Safety significant structures, systems, and components (SSCs) that could provide the identified safety functions have been selected for the conceptual design. It is anticipated that some safety SSCs identified herein will be reclassified based on hazard and accident analyses performed in support of preliminary and detailed design.« less

Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

PubMed

Feder, Stephan; Sundermann, Benedikt; Wersching, Heike; Teuber, Anja; Kugel, Harald; Teismann, Henning; Heindel, Walter; Berger, Klaus; Pfleiderer, Bettina

2017-11-01

Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity. Copyright © 2017 Elsevier B.V. All rights reserved.

Non-invasive brain stimulation to investigate language production in healthy speakers: A meta-analysis.

PubMed

Klaus, Jana; Schutter, Dennis J L G

2018-06-01

Non-invasive brain stimulation (NIBS) has become a common method to study the interrelations between the brain and language functioning. This meta-analysis examined the efficacy of transcranial magnetic stimulation (TMS) and direct current stimulation (tDCS) in the study of language production in healthy volunteers. Forty-five effect sizes from 30 studies which investigated the effects of NIBS on picture naming or verbal fluency in healthy participants were meta-analysed. Further sub-analyses investigated potential influences of stimulation type, control, target site, task, online vs. offline application, and current density of the target electrode. Random effects modelling showed a small, but reliable effect of NIBS on language production. Subsequent analyses indicated larger weighted mean effect sizes for TMS as compared to tDCS studies. No statistical differences for the other sub-analyses were observed. We conclude that NIBS is a useful method for neuroscientific studies on language production in healthy volunteers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Grey Matter Alterations Co-Localize with Functional Abnormalities in Developmental Dyslexia: An ALE Meta-Analysis

PubMed Central

Linkersdörfer, Janosch; Lonnemann, Jan; Lindberg, Sven; Hasselhorn, Marcus; Fiebach, Christian J.

2012-01-01

The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions. PMID:22916214

Potentially important periods of change in the development of social and role functioning in youth at clinical high risk for psychosis.

PubMed

Velthorst, Eva; Zinberg, Jamie; Addington, Jean; Cadenhead, Kristin S; Cannon, Tyrone D; Carrión, Ricardo E; Auther, Andrea; Cornblatt, Barbara A; McGlashan, Thomas H; Mathalon, Daniel H; Perkins, Diana O; Seidman, Larry J; Tsuang, Ming T; Walker, Elaine F; Woods, Scott W; Reichenberg, Abraham; Bearden, Carrie E

2018-02-01

The developmental course of daily functioning prior to first psychosis-onset remains poorly understood. This study explored age-related periods of change in social and role functioning. The longitudinal study included youth (aged 12-23, mean follow-up years = 1.19) at clinical high risk (CHR) for psychosis (converters [CHR-C], n = 83; nonconverters [CHR-NC], n = 275) and a healthy control group (n = 164). Mixed-model analyses were performed to determine age-related differences in social and role functioning. We limited our analyses to functioning before psychosis conversion; thus, data of CHR-C participants gathered after psychosis onset were excluded. In controls, social and role functioning improved over time. From at least age 12, functioning in CHR was poorer than in controls, and this lag persisted over time. Between ages 15 and 18, social functioning in CHR-C stagnated and diverged from that of CHR-NC, who continued to improve (p = .001). Subsequently, CHR-C lagged behind in improvement between ages 21 and 23, further distinguishing them from CHR-NC (p < .001). A similar period of stagnation was apparent for role functioning, but to a lesser extent (p = .007). The results remained consistent when we accounted for the time to conversion. Our findings suggest that CHR-C start lagging behind CHR-NC in social and role functioning in adolescence, followed by a period of further stagnation in adulthood.

Disruption of Serinc1, which facilitates serine-derived lipid synthesis, fails to alter macrophage function, lymphocyte proliferation or autoimmune disease susceptibility.

PubMed

Chu, Edward P F; Elso, Colleen M; Pollock, Abigail H; Alsayb, May A; Mackin, Leanne; Thomas, Helen E; Kay, Thomas W H; Silveira, Pablo A; Mansell, Ashley S; Gaus, Katharina; Brodnicki, Thomas C

2017-02-01

During immune cell activation, serine-derived lipids such as phosphatidylserine and sphingolipids contribute to the formation of protein signaling complexes within the plasma membrane. Altering lipid composition in the cell membrane can subsequently affect immune cell function and the development of autoimmune disease. Serine incorporator 1 (SERINC1) is a putative carrier protein that facilitates synthesis of serine-derived lipids. To determine if SERINC1 has a role in immune cell function and the development of autoimmunity, we characterized a mouse strain in which a retroviral insertion abolishes expression of the Serinc1 transcript. Expression analyses indicated that the Serinc1 transcript is readily detectable and expressed at relatively high levels in wildtype macrophages and lymphocytes. The ablation of Serinc1 expression in these immune cells, however, did not significantly alter serine-derived lipid composition or affect macrophage function and lymphocyte proliferation. Analyses of Serinc1-deficient mice also indicated that systemic ablation of Serinc1 expression did not affect viability, fertility or autoimmune disease susceptibility. These results suggest that Serinc1 is dispensable for certain immune cell functions and does not contribute to previously reported links between lipid composition in immune cells and autoimmunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in beta cell function during the proximate post-diagnosis period in persons with type 1 diabetes.

PubMed

DiMeglio, Linda A; Cheng, Peiyao; Beck, Roy W; Kollman, Craig; Ruedy, Katrina J; Slover, Robert; Aye, Tandy; Weinzimer, Stuart A; Bremer, Andrew A; Buckingham, Bruce

2016-06-01

Prior studies examining beta-cell preservation in type 1 diabetes have predominantly assessed stimulated C-peptide concentrations approximately 10 wk after diagnosis. We examined whether earlier assessments might aid in prediction of beta cell function over time. Using data from a multi-center randomized trial assessing the effect of intensive diabetes management initiated within 1 wk of diagnosis, we assessed which clinical factors predicted 90-min mixed-meal tolerance test (MMTT) stimulated C-peptide values obtained 2 and 6 wk after diagnosis. We also studied associations of these factors with C-peptide values at 1- and 2-year post-diagnosis. Data from intervention and control groups were pooled. Among 67 study participants (mean age 13.3 ± 5.7 yr, range 7.8-45.7 yr) in multivariable analyses, C-peptide increased from baseline to 2 wks and then 6 wk. C-peptide levels at these times were significantly correlated with 1- and 2-yr C-peptide concentrations (all p < 0.001), with the strongest observed associations between 6-wk C-peptide and the 1- and 2-yr values (r = 0.66 and r = 0.61, respectively). In multivariable analyses, greater baseline and 6-wk C-peptide, and older age independently predicted greater 1- and 2-yr C-peptide concentrations. C-peptide assessments close to diagnosis were predictive of subsequent C-peptide production. Our data demonstrate a clear increase in C-peptide over the initial 6 wk after diabetes diagnosis followed by a plateau. Our data do not suggest that MMTT assessments performed closer to diagnosis than 6 wk would improve prediction of subsequent residual beta cell function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

PubMed

Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

2017-01-10

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

Allelic variation contributes to bacterial host specificity

DOE PAGES

Yue, Min; Han, Xiangan; Masi, Leon De; ...

2015-10-30

Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population andmore » functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. In conclusion, together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts.« less

The Prospective Relationships Among Intrinsic Motivation, Neurocognition, and Psychosocial Functioning in Schizophrenia

PubMed Central

Nakagami, Eri; Hoe, Maanse; Brekke, John S.

2010-01-01

To address significant gaps in our understanding about how neurocognition, intrinsic motivation (IM), and psychosocial functioning are interrelated in schizophrenia, this study investigated the following questions: Is IM stable or dynamic over time? Does neurocognition predict change in IM over time? What is the association between change in neurocognition, change in IM, and change in psychosocial functioning? Finally, what is the causal structure of the relationships among neurocognition, IM, and psychosocial functioning over time? One hundred and thirty individuals diagnosed with schizophrenia or schizoaffective disorder were recruited from 4 community-based psychosocial rehabilitation programs in urban Los Angeles. Measures of neurocognition were taken at baseline and 12 months. Measures of IM, psychosocial functioning, and symptoms were taken at baseline, 6, and 12 months. Results of latent growth curve modeling analyses demonstrated that IM is dynamic over time. Baseline neurocognition was associated with the initial level of IM but did not predict the rate of change in motivation. However, baseline levels of IM predicted rates of subsequent improvement in neurocognition. Change in IM was strongly associated with change in psychosocial functioning, and change in neurocognition was associated with change in psychosocial functioning, but change in IM was not associated with change in neurocognition. Latent difference score analyses revealed that neurocognition caused changes in psychosocial functioning, and psychosocial functioning caused changes in IM. These findings improve our fundamental understanding of the relationships among these variables and contribute to intervention development for improving outcomes in schizophrenia. PMID:20462998

Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

NASA Astrophysics Data System (ADS)

Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

2015-02-01

The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

Evolution, expression analysis, and functional verification of Catharanthus roseus RLK1-like kinase (CrRLK1L) family proteins in pear (Pyrus bretchneideri).

PubMed

Kou, Xiaobing; Qi, Kaijie; Qiao, Xin; Yin, Hao; Liu, Xing; Zhang, Shaoling; Wu, Juyou

2017-07-01

The Catharanthus roseus RLK1-like kinase (CrRLK1L) family is involved in multiple processes during plant growth. However, little is known about CrRLK1L in the wood of the pear fruit tree Pyrus bretchneideri. In this study, 26 CrRLK1L gene members were identified in pear and were grouped into six subfamilies according to phylogenetic analyses. Evolutionary analysis indicated that recent whole genome duplication (WGD) and dispersed gene duplications may contribute to the expansion of the CrRLK1L gene family in pear. Moreover, tissue-specific expression analyses suggested that CrRLK1Ls are involved in the development of various pear tissues. Subsequent qRT-PCR analyses indicated that CrRLK1Ls might play important roles in pollen tube growth. Finally, experiments with antisense oligonucleotides (ASO) demonstrated that PbrCrRLK1L26 have functions in pollen tube elongation and that PbrCrRLK1L3 regulates pollen tube rupture. These results will be useful for elaborating the biological roles of CrRLK1Ls in pear growth and development. Copyright © 2017. Published by Elsevier Inc.

The response of single human cells to zero gravity

NASA Technical Reports Server (NTRS)

Montgomery, P. O., Jr.; Cook, J. E.; Reynolds, R. C.; Paul, J. S.; Hayflick, L.; Stock, D.; Schulz, W. W.; Kimzey, S. L.; Thirolf, R. G.; Rogers, T.

1974-01-01

The SO15 experiment was designed to extend observations of the effects of zero-gravity to living human cells during and subsequent to a 59-day flight on Skylab 3. A strain of diploid human embryonic lung cells, WI-38, was chosen for this purpose. The studies were concerned with observations designed to detect the effects of zero-gravity on cell growth rates and on cell structure as observed by light microscopy, transmission and scanning electron microscopy and histochemistry. Studies of the effects of zero-gravity on the cell function and the cell cycle were performed by time lapse motion picture photography and microspectrophotometry. Subsequent study of the returned living cells included karotyping, G- and C-banding, and analyses of the culture media used. Some of the living cells returned were banked by deep freeze techniques for possible future experiments.

40 CFR 85.1412 - Maintenance and submittal of records for equipment certifiers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the equipment certifier has offered to sell its certified equipment for less than the life cycle cost... during testing of the equipment and subsequent analyses based on that data, including the mileage and the... taken in implementing the quality control plan, and any subsequent analyses of that data; and (6) All in...

Cognitive Performance and Long-Term Social Functioning in Psychotic Disorder: A Three-Year Follow-Up Study

PubMed Central

Simons, Claudia J. P.; Bartels-Velthuis, Agna A.; Pijnenborg, Gerdina H. M.

2016-01-01

Objective Studies have linked cognitive functioning to everyday social functioning in psychotic disorders, but the nature of the relationships between cognition, social cognition, symptoms, and social functioning remains unestablished. Modelling the contributions of non-social and social cognitive ability in the prediction of social functioning may help in more clearly defining therapeutic targets to improve functioning. Method In a sample of 745 patients with a non-affective psychotic disorder, the associations between cognition and social cognition at baseline on the one hand, and self-reported social functioning three years later on the other, were analysed. First, case-control comparisons were conducted; associations were subsequently further explored in patients, investigating the potential mediating role of symptoms. Analyses were repeated in a subsample of 233 patients with recent-onset psychosis. Results Information processing speed and immediate verbal memory were stronger associated with social functioning in patients than in healthy controls. Most cognition variables significantly predicted social functioning at follow-up, whereas social cognition was not associated with social functioning. Symptoms were robustly associated with follow-up social functioning, with negative symptoms fully mediating most associations between cognition and follow-up social functioning. Illness duration did not moderate the strength of the association between cognitive functioning and follow-up social functioning. No associations were found between (social) cognition and follow-up social functioning in patients with recent-onset psychosis. Conclusions Although cognitive functioning is associated with later social functioning in psychotic disorder, its role in explaining social functioning outcome above negative symptoms appears only modest. In recent-onset psychosis, cognition may have a negligible role in predicting later social functioning. Moreover, social cognition tasks may not predict self-reported social functioning. PMID:27082629

A Y-Encoded Suppressor of Feminization Arose via Lineage-Specific Duplication of a Cytokinin Response Regulator in Kiwifruit[OPEN

PubMed Central

Ohtani, Haruka; Morimoto, Takuya; Beppu, Kenji; Kataoka, Ikuo

2018-01-01

Dioecy, the presence of male and female flowers on distinct individuals, has evolved independently in multiple plant lineages, and the genes involved in this differential development are just starting to be uncovered in a few species. Here, we used genomic approaches to investigate this pathway in kiwifruits (genus Actinidia). Genome-wide cataloging of male-specific subsequences, combined with transcriptome analysis, led to the identification of a type-C cytokinin response regulator as a potential sex determinant gene in this genus. Functional transgenic analyses in two model systems, Arabidopsis thaliana and Nicotiana tabacum, indicated that this gene acts as a dominant suppressor of carpel development, prompting us to name it Shy Girl (SyGI). Evolutionary analyses in a panel of Actinidia species revealed that SyGI is located in the Y-specific region of the genome and probably arose from a lineage-specific gene duplication. Comparisons with the duplicated autosomal counterpart, and with orthologs from other angiosperms, suggest that the SyGI-specific duplication and subsequent evolution of cis-elements may have played a key role in the acquisition of separate sexes in this species. PMID:29626069

[Mathematic concept model of accumulation of functional disorders associated with environmental factors].

PubMed

Zaĭtseva, N V; Trusov, P V; Kir'ianov, D A

2012-01-01

The mathematic concept model presented describes accumulation of functional disorders associated with environmental factors, plays predictive role and is designed for assessments of possible effects caused by heterogenous factors with variable exposures. Considering exposure changes with self-restoration process opens prospects of using the model to evaluate, analyse and manage occupational risks. To develop current theoretic approaches, the authors suggested a model considering age-related body peculiarities, systemic interactions of organs, including neuro-humoral regulation, accumulation of functional disorders due to external factors, rehabilitation of functions during treatment. General objective setting covers defining over a hundred unknow coefficients that characterize speed of various processes within the body. To solve this problem, the authors used iteration approach, successive identification, that starts from the certain primary approximation of the model parameters and processes subsequent updating on the basis of new theoretic and empirical knowledge.

Correlates of physical activity participation in community-dwelling older adults.

PubMed

Haley, Christy; Andel, Ross

2010-10-01

The authors examined factors related to participation in walking, gardening or yard work, and sports or exercise in 686 community-dwelling adults 60-95 years of age from Wave IV of the population-based Americans' Changing Lives Study. Logistic regression revealed that male gender, being married, and better functional health were associated with greater likelihood of participating in gardening or yard work (p < .05). Male gender, better functional health, and lower body-mass index were independently associated with greater likelihood of walking (p < .05). Increasing age, male gender, higher education, and better functional health were associated with greater likelihood of participating in sports or exercise (p < .05). Subsequent analyses yielded an interaction of functional health by gender in sport or exercise participation (p = .06), suggesting a greater association between functional health and participation in men. Gender and functional health appear to be particularly important for physical activity participation, which may be useful in guiding future research. Attention to different subgroups may be needed to promote participation in specific activities.

Recidivism following spouse abuse abatement counseling: treatment program implications.

PubMed

Hamberger, L K; Hastings, J E

1990-01-01

This paper examined demographic and personality characteristics of violence-free completers (n = 74) and violence repeating completers (n = 32) of a spouse abuse abatement counseling program. Chi-square analyses on categorical data, and analyses of variance on personality test data revealed several predicted findings. Compared to violence-free completers, recidivists reported higher levels of substance abuse both before and after treatment. Recidivists also showed evidence of higher narcissism, measured by the Narcissistic, Gregarious and Aggressive subscales of the Millon Clinical Multiaxial Inventory. Referral source (self or court) did not differentiate the two groups, nor did record of criminal activity. Subsequent discriminant function analysis, entering all predicted variables, correctly identified 65.4% of the recidivists and 73.1% of violence-free completers. Clinical and research implications of the findings are discussed.

Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

PubMed

Savage, C R; Baer, L; Keuthen, N J; Brown, H D; Rauch, S L; Jenike, M A

1999-04-01

Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

On the effectiveness of and preference for punishment and extinction components of function-based interventions.

PubMed

Hanley, Gregory P; Piazza, Cathleen C; Fisher, Wayne W; Maglieri, Kristen A

2005-01-01

The current study describes an assessment sequence that may be used to identify individualized, effective, and preferred interventions for severe problem behavior in lieu of relying on a restricted set of treatment options that are assumed to be in the best interest of consumers. The relative effectiveness of functional communication training (FCT) with and without a punishment component was evaluated with 2 children for whom functional analyses demonstrated behavioral maintenance via social positive reinforcement. The results showed that FCT plus punishment was more effective than FCT in reducing problem behavior. Subsequently, participants' relative preference for each treatment was evaluated in a concurrent-chains arrangement, and both participants demonstrated a dear preference for FCT with punishment. These findings suggest that the treatment-selection process may be guided by person-centered and evidence-based values.

Technological advances and genomics in metazoan parasites.

PubMed

Knox, D P

2004-02-01

Molecular biology has provided the means to identify parasite proteins, to define their function, patterns of expression and the means to produce them in quantity for subsequent functional analyses. Whole genome and expressed sequence tag programmes, and the parallel development of powerful bioinformatics tools, allow the execution of genome-wide between stage or species comparisons and meaningful gene-expression profiling. The latter can be undertaken with several new technologies such as DNA microarray and serial analysis of gene expression. Proteome analysis has come to the fore in recent years providing a crucial link between the gene and its protein product. RNA interference and ballistic gene transfer are exciting developments which can provide the means to precisely define the function of individual genes and, of importance in devising novel parasite control strategies, the effect that gene knockdown will have on parasite survival.

Obesity, change of body mass index and subsequent physical and mental health functioning: a 12-year follow-up study among ageing employees.

PubMed

Svärd, Anna; Lahti, Jouni; Roos, Eira; Rahkonen, Ossi; Lahelma, Eero; Lallukka, Tea; Mänty, Minna

2017-09-26

Studies suggest an association between weight change and subsequent poor physical health functioning, whereas the association with mental health functioning is inconsistent. We aimed to examine whether obesity and change of body mass index among normal weight, overweight and obese women and men associate with changes in physical and mental health functioning. The Helsinki Health Study cohort includes Finnish municipal employees aged 40 to 60 in 2000-02 (phase 1, response rate 67%). Phase 2 mail survey (response rate 82%) took place in 2007 and phase 3 in 2012 (response rate 76%). This study included 5668 participants (82% women). Seven weight change categories were formed based on body mass index (BMI) (phase 1) and weight change (BMI change ≥5%) (phase 1-2). The Short Form 36 Health Survey (SF-36) measured physical and mental health functioning. The change in health functioning (phase 1-3) score was examined with repeated measures analyses. Covariates were age, sociodemographic factors, health behaviours, and somatic ill-health. Weight gain was common among women (34%) and men (25%). Weight-gaining normal weight (-1.3 points), overweight (-1.3 points) and obese (-3.6 points) women showed a greater decline in physical component summary scores than weight-maintaining normal weight women. Among weight-maintainers, only obese (-1.8 points) women showed a greater decline than weight-maintaining normal weight women. The associations were similar, but statistically non-significant for obese men. No statistically significant differences in the change in mental health functioning occurred. Preventing weight gain likely helps maintaining good physical health functioning and work ability.

Fluorescence and afterglow of Ca2Sn2Al2O9:Mn2+

NASA Astrophysics Data System (ADS)

Takemoto, Minoru; Iseki, Takahiro

2018-03-01

By using a polymerized complex method, we synthesized manganese (Mn)-doped Ca2Sn2Al2O9, which exhibits yellow fluorescence and afterglow at room temperature when excited by UV radiation. The material emits a broad, featureless fluorescence band centered at 564 nm, which we attribute to the presence of Mn2+ ions. The afterglow decay is well fit by a power-law function, rather than an exponential function. In addition, thermoluminescence analyses demonstrate that two different types of electron traps form in this material. Based on experimental results, we conclude that the fluorescence and afterglow both result from thermally assisted tunneling, in which trapped electrons are thermally excited to higher-level traps and subsequently tunnel to recombination centers.

Plant peptide hormone signalling.

PubMed

Motomitsu, Ayane; Sawa, Shinichiro; Ishida, Takashi

2015-01-01

The ligand-receptor-based cell-to-cell communication system is one of the most important molecular bases for the establishment of complex multicellular organisms. Plants have evolved highly complex intercellular communication systems. Historical studies have identified several molecules, designated phytohormones, that function in these processes. Recent advances in molecular biological analyses have identified phytohormone receptors and signalling mediators, and have led to the discovery of numerous peptide-based signalling molecules. Subsequent analyses have revealed the involvement in and contribution of these peptides to multiple aspects of the plant life cycle, including development and environmental responses, similar to the functions of canonical phytohormones. On the basis of this knowledge, the view that these peptide hormones are pivotal regulators in plants is becoming increasingly accepted. Peptide hormones are transcribed from the genome and translated into peptides. However, these peptides generally undergo further post-translational modifications to enable them to exert their function. Peptide hormones are expressed in and secreted from specific cells or tissues. Apoplastic peptides are perceived by specialized receptors that are located at the surface of target cells. Peptide hormone-receptor complexes activate intracellular signalling through downstream molecules, including kinases and transcription factors, which then trigger cellular events. In this chapter we provide a comprehensive summary of the biological functions of peptide hormones, focusing on how they mature and the ways in which they modulate plant functions. © 2015 Authors; published by Portland Press Limited.

Bidirectional-Compounding Effects of Rumination and Negative Emotion in Predicting Impulsive Behavior: Implications for Emotional Cascades.

PubMed

Selby, Edward A; Kranzler, Amy; Panza, Emily; Fehling, Kara B

2016-04-01

Influenced by chaos theory, the emotional cascade model proposes that rumination and negative emotion may promote each other in a self-amplifying cycle that increases over time. Accordingly, exponential-compounding effects may better describe the relationship between rumination and negative emotion when they occur in impulsive persons, and predict impulsive behavior. Forty-seven community and undergraduate participants who reported frequent engagement in impulsive behaviors monitored their ruminative thoughts and negative emotion multiple times daily for two weeks using digital recording devices. Hypotheses were tested using cross-lagged mixed model analyses. Findings indicated that rumination predicted subsequent elevations in rumination that lasted over extended periods of time. Rumination and negative emotion predicted increased levels of each other at subsequent assessments, and exponential functions for these associations were supported. Results also supported a synergistic effect between rumination and negative emotion, predicting larger elevations in subsequent rumination and negative emotion than when one variable alone was elevated. Finally, there were synergistic effects of rumination and negative emotion in predicting number of impulsive behaviors subsequently reported. These findings are consistent with the emotional cascade model in suggesting that momentary rumination and negative emotion progressively propagate and magnify each other over time in impulsive people, promoting impulsive behavior. © 2014 Wiley Periodicals, Inc.

Early post-stroke cognition in stroke rehabilitation patients predicts functional outcome at 13 months.

PubMed

Wagle, Jørgen; Farner, Lasse; Flekkøy, Kjell; Bruun Wyller, Torgeir; Sandvik, Leiv; Fure, Brynjar; Stensrød, Brynhild; Engedal, Knut

2011-01-01

To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors. 163 stroke rehabilitation patients underwent a structured neuropsychological examination 2-3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value <0.05, from the biological and functional models). A combined model of 4 variables best predicted long-term functional outcome with explained variance of 49%: neurological impairment (National Institute of Health Stroke Scale; β = 0.402, p < 0.001), age (β = 0.233, p = 0.001), post-stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = -0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = -0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = -0.484, p < 0.001) and Figure Copy (β = -0.233, p = 0.002) raw scores at baseline explained 42% of the variance in mRS scores at follow-up. Early post-stroke cognitive functioning as measured by the RBANS is a significant and independent predictor of long-term functional post-stroke outcome. Copyright © 2011 S. Karger AG, Basel.

Quantification of Interactions between Dynamic Cellular Network Functionalities by Cascaded Layering

PubMed Central

Prescott, Thomas P.; Lang, Moritz; Papachristodoulou, Antonis

2015-01-01

Large, naturally evolved biomolecular networks typically fulfil multiple functions. When modelling or redesigning such systems, functional subsystems are often analysed independently first, before subsequent integration into larger-scale computational models. In the design and analysis process, it is therefore important to quantitatively analyse and predict the dynamics of the interactions between integrated subsystems; in particular, how the incremental effect of integrating a subsystem into a network depends on the existing dynamics of that network. In this paper we present a framework for simulating the contribution of any given functional subsystem when integrated together with one or more other subsystems. This is achieved through a cascaded layering of a network into functional subsystems, where each layer is defined by an appropriate subset of the reactions. We exploit symmetries in our formulation to exhaustively quantify each subsystem’s incremental effects with minimal computational effort. When combining subsystems, their isolated behaviour may be amplified, attenuated, or be subject to more complicated effects. We propose the concept of mutual dynamics to quantify such nonlinear phenomena, thereby defining the incompatibility and cooperativity between all pairs of subsystems when integrated into any larger network. We exemplify our theoretical framework by analysing diverse behaviours in three dynamic models of signalling and metabolic pathways: the effect of crosstalk mechanisms on the dynamics of parallel signal transduction pathways; reciprocal side-effects between several integral feedback mechanisms and the subsystems they stabilise; and consequences of nonlinear interactions between elementary flux modes in glycolysis for metabolic engineering strategies. Our analysis shows that it is not sufficient to just specify subsystems and analyse their pairwise interactions; the environment in which the interaction takes place must also be explicitly defined. Our framework provides a natural representation of nonlinear interaction phenomena, and will therefore be an important tool for modelling large-scale evolved or synthetic biomolecular networks. PMID:25933116

MolabIS--an integrated information system for storing and managing molecular genetics data.

PubMed

Truong, Cong V C; Groeneveld, Linn F; Morgenstern, Burkhard; Groeneveld, Eildert

2011-10-31

Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org.

MolabIS - An integrated information system for storing and managing molecular genetics data

PubMed Central

2011-01-01

Background Long-term sample storage, tracing of data flow and data export for subsequent analyses are of great importance in genetics studies. Therefore, molecular labs do need a proper information system to handle an increasing amount of data from different projects. Results We have developed a molecular labs information management system (MolabIS). It was implemented as a web-based system allowing the users to capture original data at each step of their workflow. MolabIS provides essential functionality for managing information on individuals, tracking samples and storage locations, capturing raw files, importing final data from external files, searching results, accessing and modifying data. Further important features are options to generate ready-to-print reports and convert sequence and microsatellite data into various data formats, which can be used as input files in subsequent analyses. Moreover, MolabIS also provides a tool for data migration. Conclusions MolabIS is designed for small-to-medium sized labs conducting Sanger sequencing and microsatellite genotyping to store and efficiently handle a relative large amount of data. MolabIS not only helps to avoid time consuming tasks but also ensures the availability of data for further analyses. The software is packaged as a virtual appliance which can run on different platforms (e.g. Linux, Windows). MolabIS can be distributed to a wide range of molecular genetics labs since it was developed according to a general data model. Released under GPL, MolabIS is freely available at http://www.molabis.org. PMID:22040322

Computationally inexpensive identification of noninformative model parameters by sequential screening

NASA Astrophysics Data System (ADS)

Cuntz, Matthias; Mai, Juliane; Zink, Matthias; Thober, Stephan; Kumar, Rohini; Schäfer, David; Schrön, Martin; Craven, John; Rakovec, Oldrich; Spieler, Diana; Prykhodko, Vladyslav; Dalmasso, Giovanni; Musuuza, Jude; Langenberg, Ben; Attinger, Sabine; Samaniego, Luis

2015-08-01

Environmental models tend to require increasing computational time and resources as physical process descriptions are improved or new descriptions are incorporated. Many-query applications such as sensitivity analysis or model calibration usually require a large number of model evaluations leading to high computational demand. This often limits the feasibility of rigorous analyses. Here we present a fully automated sequential screening method that selects only informative parameters for a given model output. The method requires a number of model evaluations that is approximately 10 times the number of model parameters. It was tested using the mesoscale hydrologic model mHM in three hydrologically unique European river catchments. It identified around 20 informative parameters out of 52, with different informative parameters in each catchment. The screening method was evaluated with subsequent analyses using all 52 as well as only the informative parameters. Subsequent Sobol's global sensitivity analysis led to almost identical results yet required 40% fewer model evaluations after screening. mHM was calibrated with all and with only informative parameters in the three catchments. Model performances for daily discharge were equally high in both cases with Nash-Sutcliffe efficiencies above 0.82. Calibration using only the informative parameters needed just one third of the number of model evaluations. The universality of the sequential screening method was demonstrated using several general test functions from the literature. We therefore recommend the use of the computationally inexpensive sequential screening method prior to rigorous analyses on complex environmental models.

Computationally inexpensive identification of noninformative model parameters by sequential screening

NASA Astrophysics Data System (ADS)

Mai, Juliane; Cuntz, Matthias; Zink, Matthias; Thober, Stephan; Kumar, Rohini; Schäfer, David; Schrön, Martin; Craven, John; Rakovec, Oldrich; Spieler, Diana; Prykhodko, Vladyslav; Dalmasso, Giovanni; Musuuza, Jude; Langenberg, Ben; Attinger, Sabine; Samaniego, Luis

2016-04-01

Environmental models tend to require increasing computational time and resources as physical process descriptions are improved or new descriptions are incorporated. Many-query applications such as sensitivity analysis or model calibration usually require a large number of model evaluations leading to high computational demand. This often limits the feasibility of rigorous analyses. Here we present a fully automated sequential screening method that selects only informative parameters for a given model output. The method requires a number of model evaluations that is approximately 10 times the number of model parameters. It was tested using the mesoscale hydrologic model mHM in three hydrologically unique European river catchments. It identified around 20 informative parameters out of 52, with different informative parameters in each catchment. The screening method was evaluated with subsequent analyses using all 52 as well as only the informative parameters. Subsequent Sobol's global sensitivity analysis led to almost identical results yet required 40% fewer model evaluations after screening. mHM was calibrated with all and with only informative parameters in the three catchments. Model performances for daily discharge were equally high in both cases with Nash-Sutcliffe efficiencies above 0.82. Calibration using only the informative parameters needed just one third of the number of model evaluations. The universality of the sequential screening method was demonstrated using several general test functions from the literature. We therefore recommend the use of the computationally inexpensive sequential screening method prior to rigorous analyses on complex environmental models.

SASH1, a new potential link between smoking and atherosclerosis.

PubMed

Weidmann, Henri; Touat-Hamici, Zahia; Durand, Herve; Mueller, Christian; Chardonnet, Solenne; Pionneau, Cedric; Charlotte, Frédéric; Janssen, Klaus-Peter; Verdugo, Ricardo; Cambien, Francois; Blankenberg, Stefan; Tiret, Laurence; Zeller, Tanja; Ninio, Ewa

2015-10-01

We have previously reported that SASH1 expression is increased in circulating human monocytes from smokers and was positively correlated with the number of carotid atherosclerotic plaques. The aim of this study was to further validate the link between smoking, SASH1 and atherosclerosis within the vascular wall and to assess the impact of SASH1 expression on endothelial cell functions. Human carotids with atherosclerotic plaques were obtained from 58 patients (45 of them with known smoking status: smoker, non-smoker, ex-smokers), and were processed for gene expression analyses and immunostaining. To investigate its function, SASH1 was silenced in human aortic endothelial cells (HAECs) using two different siRNA and subcellular localization of SASH1 was determined by immunostaining and subcellular fractionation. Subsequently the transcriptomic analyses and functional experiments (wound healing, WST-1 proliferation or Matrigel assays) were performed to characterize SASH1 function. SASH1 was expressed in human vascular cells (HAECs, smooth muscle cells) and in monocytes/macrophages. Its tissue expression was significantly higher in the atherosclerotic carotids of smokers compared to non-smokers (p < 0.01). In HAECs, SASH1 was expressed mostly in the cytoplasm and SASH1 knockdown resulted in an increased cell migration, proliferation and angiogenesis. Transcriptomic and pathway analyses showed that SASH1 silencing results in a decreased CYP1A1 expression possibly through the inhibition of TP53 activity. We showed that SASH1 expression is increased in atherosclerotic carotids in smokers and its silencing affects endothelial angiogenic functions; therefore we provide a potential link between smoking and atherosclerosis through SASH1 expression. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Plasma levels of cytokines and chemokines and the risk of mortality in HIV-infected individuals: a case-control analysis nested in a large clinical trial

PubMed Central

French, MA; Cozzi-Lepri, A; Arduino, RC; Johnson, M; Achhra, AC; Landay, A

2015-01-01

Background All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin (IL)-6, which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs. Methods Baseline plasma samples from 142 participants enrolled into the SMART study who subsequently died, and 284 matched controls, were assayedfor levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/pro-inflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death. Results Higher plasma levels of pro-inflammatory cytokines (IL-6 and tumour necrosis factor-alpha) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with IL-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of HCV status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group. Conclusions While plasma levels of IL-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs. PMID:25695873

Day-to-day relations between stress and sleep and the mediating role of perseverative cognition.

PubMed

Van Laethem, Michelle; Beckers, Debby G J; van Hooff, Madelon L M; Dijksterhuis, Ap; Geurts, Sabine A E

2016-08-01

The goals of this longitudinal diary-based study were to shed light on the day-level relationship between stress and subsequent sleep, and to examine whether perseverative cognition is a mediating factor in this relation. A total of 44 Dutch PhD students were followed during a two-month period, from one month before their public thesis defense (ie, a stressful life event), until one month thereafter. Participants completed short evening and morning questionnaires on eight occasions (in anticipation of and following the defense), including questions about day-level stress, sleep quality, and perseverative cognition. Objective sleep parameters were collected with the SenseWear Pro Armband. Multilevel analysis was used to analyze daily observations nested within individuals. Analyses revealed that day-level stress was not directly related to subsequent subjective sleep indicators or to subsequent objective sleep indicators. Day-level stress was significantly associated with day-level perseverative cognition, and daily variations in perseverative cognition were significantly related to several day-level objective sleep parameters (sleep efficiency, marginally to number of awakenings, and wake after sleep onset), and to several day-level subjective sleep parameters (sleep quality, number of awakenings, wake after sleep onset). Finally, mediation analyses using path analysis suggested that, on the day level, perseverative cognition functions as a mediator between stress and several sleep parameters, namely, subjective sleep quality, objective sleep efficiency, and subjective wake after sleep onset. Perseverative cognition is a promising explanatory mechanism linking day-level stress to subjective and objective measures of sleep. Copyright © 2016 Elsevier B.V. All rights reserved.

Mapping the changed hubs and corresponding functional connectivity in idiopathic restless legs syndrome.

PubMed

Liu, Chunyan; Wang, Jiaojian; Hou, Yue; Qi, Zhigang; Wang, Li; Zhan, Shuqin; Wang, Rong; Wang, Yuping

2018-05-01

The hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of leg discomfort symptoms in restless legs syndrome (RLS) patients remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in RLS. First, we constructed the whole-brain voxelwise functional connectivity and calculated a functional connectivity strength (FCS) map in each of 16 drug-naive idiopathic RLS patients and 26 gender- and age-matched healthy control (HC) subjects. Next, a two-sample t test was applied to compare the FCS maps between HC and RLS patients, and to identify significant changes in FCS in RLS patients. To further elucidate the corresponding changes in the functional connectivity patterns of the aberrant hubs in RLS patients, whole-brain resting-state functional connectivity analyses for the hub areas were performed. The hub analysis revealed decreased FCS in the cuneus, fusiform gyrus, paracentral lobe, and precuneus, and increased FCS in the superior frontal gyrus and thalamus in idiopathic drug-naive RLS patients. Subsequent functional connectivity analyses revealed decreased functional connectivity in sensorimotor and visual processing networks and increased functional connectivity in the affective cognitive network and cerebellar-thalamic circuit. Furthermore, the mean FCS value in the superior frontal gyrus was significantly correlated with Hamilton Anxiety Rating Scale scores in RLS patients, and the mean FCS value in the fusiform gyrus was significantly correlated with Hamilton Depression Rating Scale scores. These findings may provide novel insight into the pathophysiology of RLS. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional Analyses of a Novel CITED2 Nonsynonymous Mutation in Chinese Tibetan Patients with Congenital Heart Disease.

PubMed

Liu, Shiming; Su, Zhaobing; Tan, Sainan; Ni, Bin; Pan, Hong; Liu, Beihong; Wang, Jing; Xiao, Jianmin; Chen, Qiuhong

2017-08-01

CITED2 gene is an important cardiac transcription factor that plays a fundamental role in the formation and development of embryonic cardiovascular. Previous studies have showed that knock-out of CITED2 in mice might result in various cardiac malformations. However, the mechanisms of CITED2 mutation on congenital heart disease (CHD) in Chinese Tibetan population are still poorly understood. In the present study, 187 unrelated Tibetan patients with CHD and 200 unrelated Tibetan healthy controls were screened for variants in the CITED2 gene; we subsequently identified one potential disease-causing mutation p.G143A in a 6-year-old girl with PDA and functional analyses of the mutation were carried out. Our study showed that the novel mutation of CITED2 significantly enhanced the expression activity of vascular endothelial growth factor (VEGF) under the role of co-receptor hypoxia inducible factor 1-aipha (HIF-1A), which is closely related with embryonic cardiac development. As a result, CITED2 gene mutation may play a significant role in the development of pediatric congenital heart disease.

Adaptive Covariation between the Coat and Movement Proteins of Prunus Necrotic Ringspot Virus

PubMed Central

Codoñer, Francisco M.; Fares, Mario A.; Elena, Santiago F.

2006-01-01

The relative functional and/or structural importance of different amino acid sites in a protein can be assessed by evaluating the selective constraints to which they have been subjected during the course of evolution. Here we explore such constraints at the linear and three-dimensional levels for the movement protein (MP) and coat protein (CP) encoded by RNA 3 of prunus necrotic ringspot ilarvirus (PNRSV). By a maximum-parsimony approach, the nucleotide sequences from 46 isolates of PNRSV varying in symptomatology, host tree, and geographic origin have been analyzed and sites under different selective pressures have been identified in both proteins. We have also performed covariation analyses to explore whether changes in certain amino acid sites condition subsequent variation in other sites of the same protein or the other protein. These covariation analyses shed light on which particular amino acids should be involved in the physical and functional interaction between MP and CP. Finally, we discuss these findings in the light of what is already known about the implication of certain sites and domains in structure and protein-protein and RNA-protein interactions. PMID:16731922

Adaptive covariation between the coat and movement proteins of prunus necrotic ringspot virus.

PubMed

Codoñer, Francisco M; Fares, Mario A; Elena, Santiago F

2006-06-01

The relative functional and/or structural importance of different amino acid sites in a protein can be assessed by evaluating the selective constraints to which they have been subjected during the course of evolution. Here we explore such constraints at the linear and three-dimensional levels for the movement protein (MP) and coat protein (CP) encoded by RNA 3 of prunus necrotic ringspot ilarvirus (PNRSV). By a maximum-parsimony approach, the nucleotide sequences from 46 isolates of PNRSV varying in symptomatology, host tree, and geographic origin have been analyzed and sites under different selective pressures have been identified in both proteins. We have also performed covariation analyses to explore whether changes in certain amino acid sites condition subsequent variation in other sites of the same protein or the other protein. These covariation analyses shed light on which particular amino acids should be involved in the physical and functional interaction between MP and CP. Finally, we discuss these findings in the light of what is already known about the implication of certain sites and domains in structure and protein-protein and RNA-protein interactions.

Characterizing the role of the hippocampus during episodic simulation and encoding.

PubMed

Thakral, Preston P; Benoit, Roland G; Schacter, Daniel L

2017-12-01

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior-posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation-related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval. © 2017 Wiley Periodicals, Inc.

Developmental fMRI study of episodic verbal memory encoding in children.

PubMed

Maril, A; Davis, P E; Koo, J J; Reggev, N; Zuckerman, M; Ehrenfeld, L; Mulkern, R V; Waber, D P; Rivkin, M J

2010-12-07

Understanding the maturation and organization of cognitive function in the brain is a central objective of both child neurology and developmental cognitive neuroscience. This study focuses on episodic memory encoding of verbal information by children, a cognitive domain not previously studied using fMRI. Children from 7 to 19 years of age were scanned at 1.5-T field strength using event-related fMRI while performing a novel verbal memory encoding paradigm in which words were incidentally encoded. A subsequent memory analysis was performed. SPM2 was utilized for whole brain and region-of-interest analyses of data. Both whole-sample intragroup analyses and intergroup analyses of the sample divided into 2 subgroups by age were conducted. Importantly, behavioral memory performance was equal across the age range of children studied. Encoding-related activation in the left hippocampus and bilateral basal ganglia declined as age increased. In addition, while robust blood oxygen level-dependent signal was found in left prefrontal cortex with task performance, no encoding-related age-modulated prefrontal activation was observed in either hemisphere. These data are consistent with a developmental pattern of verbal memory encoding function in which left hippocampal and bilateral basal ganglionic activations are more robust earlier in childhood but then decline with age. No encoding-related activation was found in prefrontal cortex which may relate to this region's recognized delay in biologic maturation in humans. These data represent the first fMRI demonstration of verbal encoding function in children and are relevant developmentally and clinically.

Potential biomarkers of ageing.

PubMed

Simm, Andreas; Nass, Norbert; Bartling, Babett; Hofmann, Britt; Silber, Rolf-Edgar; Navarrete Santos, Alexander

2008-03-01

Life span in individual humans is very heterogeneous.Thus, the ageing rate, measured as the decline of functional capacity and stress resistance, is different in every individual. There have been attempts made to analyse this individual age, the so-called biological age, in comparison to chronological age. Biomarkers of ageing should help to characterise this biological age and, as age is a major risk factor in many degenerative diseases,could be subsequently used to identify individuals at high risk of developing age-associated diseases or disabilities. Markers based on oxidative stress, protein glycation,inflammation, cellular senescence and hormonal deregulation are discussed.

Advanced correlation grid: Analysis and visualisation of functional connectivity among multiple spike trains.

PubMed

Masud, Mohammad Shahed; Borisyuk, Roman; Stuart, Liz

2017-07-15

This study analyses multiple spike trains (MST) data, defines its functional connectivity and subsequently visualises an accurate diagram of connections. This is a challenging problem. For example, it is difficult to distinguish the common input and the direct functional connection of two spike trains. The new method presented in this paper is based on the traditional pairwise cross-correlation function (CCF) and a new combination of statistical techniques. First, the CCF is used to create the Advanced Correlation Grid (ACG) correlation where both the significant peak of the CCF and the corresponding time delay are used for detailed analysis of connectivity. Second, these two features of functional connectivity are used to classify connections. Finally, the visualization technique is used to represent the topology of functional connections. Examples are presented in the paper to demonstrate the new Advanced Correlation Grid method and to show how it enables discrimination between (i) influence from one spike train to another through an intermediate spike train and (ii) influence from one common spike train to another pair of analysed spike trains. The ACG method enables scientists to automatically distinguish between direct connections from spurious connections such as common source connection and indirect connection whereas existing methods require in-depth analysis to identify such connections. The ACG is a new and effective method for studying functional connectivity of multiple spike trains. This method can identify accurately all the direct connections and can distinguish common source and indirect connections automatically. Copyright © 2017 Elsevier B.V. All rights reserved.

[Implementation of functional autonomy measurement system: barriers and facilitators in PISE-Dordogne project].

PubMed

Gervais, Pauline; Hébert, Réjean; Lamontagne, Julie; Tousignant, Michel

2011-12-01

The objectives of the study were to identify the adjustments made during the implantation and the conditions favouring or limiting the SMAF utilisation. A multiqualitative quote was developed. The Functional autonomy measurement system (SMAF) was implanted in 11 French medico-social establishments. Analyses were made with the mixed type thematic method from Miles and Huberman. Principal adjustments that have been made during implantation concern the informatics assistance and clinical support. Strategic, organizational and individual factors explained adhesion level of actors and the subsequent flow of implantation. Establishment of SMAF and of the software eSMAF® in the medico-social establishments rests on a certain number of conditions which could be identified during the study. These conditions made it possible to work out structured recommendations for future implementations.

Temperature mediated moose survival in Northeastern Minnesota

USGS Publications Warehouse

Lenarz, M.S.; Nelson, M.E.; Schrage, M.W.; Edwards, A.J.

2009-01-01

The earth is in the midst of a pronounced warming trend and temperatures in Minnesota, USA, as elsewhere, are projected to increase. Northern Minnesota represents the southern edge to the circumpolar distribution of moose (Alces alces), a species intolerant of heat. Moose increase their metabolic rate to regulate their core body temperature as temperatures rise. We hypothesized that moose survival rates would be a function of the frequency and magnitude that ambient temperatures exceeded the upper critical temperature of moose. We compared annual and seasonal moose survival in northeastern Minnesota between 2002 and 2008 with a temperature metric. We found that models based on January temperatures above the critical threshold were inversely correlated with subsequent survival and explained >78 of variability in spring, fall, and annual survival. Models based on late-spring temperatures also explained a high proportion of survival during the subsequent fall. A model based on warm-season temperatures was important in explaining survival during the subsequent winter. Our analyses suggest that temperatures may have a cumulative influence on survival. We expect that continuation or acceleration of current climate trends will result in decreased survival, a decrease in moose density, and ultimately, a retreat of moose northward from their current distribution.

Early prediction of cerebral palsy by computer-based video analysis of general movements: a feasibility study.

PubMed

Adde, Lars; Helbostad, Jorunn L; Jensenius, Alexander R; Taraldsen, Gunnar; Grunewaldt, Kristine H; Støen, Ragnhild

2010-08-01

The aim of this study was to investigate the predictive value of a computer-based video analysis of the development of cerebral palsy (CP) in young infants. A prospective study of general movements used recordings from 30 high-risk infants (13 males, 17 females; mean gestational age 31wks, SD 6wks; range 23-42wks) between 10 and 15 weeks post term when fidgety movements should be present. Recordings were analysed using computer vision software. Movement variables, derived from differences between subsequent video frames, were used for quantitative analyses. CP status was reported at 5 years. Thirteen infants developed CP (eight hemiparetic, four quadriparetic, one dyskinetic; seven ambulatory, three non-ambulatory, and three unknown function), of whom one had fidgety movements. Variability of the centroid of motion had a sensitivity of 85% and a specificity of 71% in identifying CP. By combining this with variables reflecting the amount of motion, specificity increased to 88%. Nine out of 10 children with CP, and for whom information about functional level was available, were correctly predicted with regard to ambulatory and non-ambulatory function. Prediction of CP can be provided by computer-based video analysis in young infants. The method may serve as an objective and feasible tool for early prediction of CP in high-risk infants.

Memory and executive functions in persons with type 2 diabetes: a meta-analysis.

PubMed

Sadanand, Shilpa; Balachandar, Rakesh; Bharath, Srikala

2016-02-01

Literature suggests that persons with type 2 diabetes mellitus (T2DM) are at risk for cognitive impairment, hence dementia. Common domains reported to be affected in those with T2DM are memory and executive functions. The extent of influence of T2DM on these domains has varied among studies. A systematic review and meta-analysis was carried out to understand whether sub-domains contributed to the variations observed in published research. We searched 'PubMed', 'ScienceDirect', 'SciVerseHub', 'Psychinfo', 'Proquest' 'Ebsco' and 'J-gate Plus' databases for published studies on cognition and T2DM among persons aged 50 years and older. Memory, executive functions and processing speed domain and sub-domain scores were extracted; effect sizes (Cohen's d) were calculated and analysed. Eight hundred seventeen articles were found. After various levels of filtering, 15 articles met the inclusion criteria for quantitative analyses. The analyses indicated that in comparison to controls, persons with T2DM showed decrements in episodic memory (d = -0.51), logical memory (d = -0.24), sub-domain of executive functions which included phonemic fluency (d = -0.35) and cognitive flexibility (d = 0.52), and speed of processing (d = -0.22). We found no difference in the sub-domains of verbal short-term memory and working memory. The meta-analysis revealed a detrimental effect of T2DM on cognitive sub-domains, namely, episodic memory and cognitive flexibility. There was a trend for the logical memory, phonemic fluency and processing speed to be affected. The analysis indicates that T2DM is a detrimental factor on certain cognitive sub-domains, rendering the person vulnerable to subsequent dementia. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Autobiographical memory functions in young Japanese men and women.

PubMed

Maki, Yoichi; Kawasaki, Yayoi; Demiray, Burcu; Janssen, Steve M J

2015-01-01

The present study examined whether the three major functions of autobiographical memory observed in Western societies (i.e., directing-behaviour, social-bonding and self-continuity) also exist in an East Asian society. Two self-report measures were used to assess the autobiographical memory functions of Japanese men and women. Japanese young adults (N = 451, ages 17-28 years) first completed the original Thinking About Life Experiences (TALE) Questionnaire. They subsequently received three TALE items that represented memory functions and attempted to recall a specific instance of memory recall for each item. Confirmatory factor analyses on the TALE showed that the three functions were replicated in the current sample. However, Japanese participants reported lower levels of all three functions than American participants in a previous study. We also explored whether there was an effect of gender in this Japanese sample. Women reported higher levels of the self-continuity and social-bonding functions than men. Finally, participants recalled more specific instances of memory recall for the TALE items that had received higher ratings on the TALE, suggesting that the findings on the first measure were supported by the second measure. Results are discussed in relation to the functional approach to autobiographical memory in a cross-cultural context.

Functioning before and after a major depressive episode: pre-existing vulnerability or scar? A prospective three-wave population-based study.

PubMed

Bos, E H; Ten Have, M; van Dorsselaer, S; Jeronimus, B F; de Graaf, R; de Jonge, P

2018-01-14

The vulnerability hypothesis suggests that impairments after remission of depressive episodes reflect a pre-existing vulnerability, while the scar hypothesis proposes that depression leaves residual impairments that confer risk of subsequent episodes. We prospectively examined vulnerability and scar effects in mental and physical functioning in a representative Dutch population sample. Three waves were used from the Netherlands Mental Health Survey and Incidence Study-2, a population-based study with a 6-years follow-up. Mental and physical functioning were assessed with the Medical Outcomes Study Short Form (SF-36). Major depressive disorder (MDD) was assessed with the Composite International Diagnostic Interview 3.0. Vulnerability effects were examined by comparing healthy controls (n = 2826) with individuals who developed a first-onset depressive episode during first follow-up but did not have a lifetime diagnosis of MDD at baseline (n = 181). Scarring effects were examined by comparing pre- and post-morbid functioning in individuals who developed a depressive episode after baseline that was remitted at the third wave (n = 108). Both mental (B = -5.4, s.e. = 0.9, p < 0.001) and physical functioning (B = -8.2, s.e. = 1.1, p < 0.001) at baseline were lower in individuals who developed a first depressive episode after baseline compared with healthy controls. This effect was most pronounced in people who developed a severe episode. No firm evidence of scarring in mental or physical functioning was found. In unadjusted analyses, physical functioning was still lowered post-morbidly (B = -5.1, s.e. = 2.1, p = 0.014), but this effect disappeared in adjusted analyses. Functional impairments after remission of depression seem to reflect a pre-existing vulnerability rather than a scar.

Evaluating Florida's Medicaid Provider Services Network Demonstration

PubMed Central

Paul Duncan, R; Lemak, Christy H; Bruce Vogel, W; Johnson, Christopher E; Hall, Allyson G; Porter, Colleen K

2008-01-01

Research Objective To evaluate the design, development, and implementation of Florida's Medicaid provider service network (PSN) demonstration, and the implications of that demonstration for subsequent Medicaid Reform in Florida. Data Sources, Data Collection Organizational analyses were based on archival and enrollment data obtained from Florida's Medicaid program and the South Florida Community Care Network, as well as key informant interviews. Closely related fiscal analyses utilized Medicaid claims data from March 1999 through October 2001 extracted from the Florida Medicaid Management Information System. Study Design The organizational analyses reported here were based on a structured case study research design. Principal Findings Almost every aspect of the development of the new organizational form (PSN) took longer and was more difficult than anticipated. Prior organizational experience with insurance functions proved to be an asset. While fiscal analyses indicated that the program saved the state of Florida a significant amount of money, tracking the precise origin of the savings proved to be challenging. Conclusions By most standards, the PSN program was observed to meet its stated objectives. Based in part on this conclusion, the state chose to extend the use of PSNs within its 2006 Medicaid Reform initiative. PMID:18199192

Pre-Session Satiation as a Treatment for Stereotypy During Group Activities.

PubMed

Rispoli, Mandy; Camargo, Síglia Hoher; Neely, Leslie; Gerow, Stephanie; Lang, Russell; Goodwyn, Fara; Ninci, Jennifer

2014-05-01

Individuals with developmental disabilities may engage in automatically reinforced behaviors that may interfere with learning opportunities. Manipulation of motivating operations has been shown to reduce automatically maintained behavior in some individuals. Considering behavioral indicators of satiation may assist in identifying the point at which an abolishing operation has begun to effect behavior. The purpose of this study was to evaluate the effects of pre-session satiation of automatic reinforcement on subsequent levels of stereotypy and activity engagement during group activities for three males ages 5 to 13 years with developmental disabilities. Following functional analyses with analogue conditions, an alternating treatment design compared a pre-session access to stereotypy condition with a no-pre-session access condition prior to group activity sessions. Results indicated that pre-session satiation of the putative reinforcer produced by stereotypy was effective in decreasing stereotypy and increasing activity engagement during subsequent group activities for all participants. These findings add to the literature supporting the effectiveness of abolishing operations to decrease automatically maintained stereotypy. © The Author(s) 2013.

Working memory overload: fronto-limbic interactions and effects on subsequent working memory function.

PubMed

Yun, Richard J; Krystal, John H; Mathalon, Daniel H

2010-03-01

The human working memory system provides an experimentally useful model for examination of neural overload effects on subsequent functioning of the overloaded system. This study employed functional magnetic resonance imaging in conjunction with a parametric working memory task to characterize the behavioral and neural effects of cognitive overload on subsequent cognitive performance, with particular attention to cognitive-limbic interactions. Overloading the working memory system was associated with varying degrees of subsequent decline in performance accuracy and reduced activation of brain regions central to both task performance and suppression of negative affect. The degree of performance decline was independently predicted by three separate factors operating during the overload condition: the degree of task failure, the degree of amygdala activation, and the degree of inverse coupling between the amygdala and dorsolateral prefrontal cortex. These findings suggest that vulnerability to overload effects in cognitive functioning may be mediated by reduced amygdala suppression and subsequent amygdala-prefrontal interaction.

Disentangling the Role of Melatonin and its Receptor MTNR1B in Type 2 Diabetes: Still a Long Way to Go?

PubMed

Bonnefond, Amélie; Froguel, Philippe

2017-10-23

Type 2 diabetes (T2D) is a complex genetic metabolic disorder. T2D heritability has been estimated around 40-70%. In the last decade, exponential progress has been made in identifying T2D genetic determinants, through genome-wide association studies (GWAS). Among single-nucleotide polymorphisms mostly associated with T2D risk, rs10830963 is located in the MTNR1B gene, encoding one of the two receptors of melatonin, a neurohormone involved in circadian rhythms. Subsequent studies aiming to disentangle the role of MTNR1B in T2D pathophysiology led to controversies. In this review, we will tackle them and will try to give some directions to get a better view of MTNR1B contribution to T2D pathophysiology. Recent studies either based on genetic/genomic analyses, clinical/epidemiology data, functional analyses at rs10830963 locus, insulin secretion assays in response to melatonin (involving or not MTNR1B) or animal model analyses have led to strong controversies at each level of interpretation. We discuss possible caveats in these studies and present ways to go beyond these issues, towards a better understanding of T2D molecular mechanisms, keeping in mind that melatonin is a versatile hormone and regulates many functions via its primary role in the body clock.

Definition and characterization of an extended social-affective default network.

PubMed

Amft, Maren; Bzdok, Danilo; Laird, Angela R; Fox, Peter T; Schilbach, Leonhard; Eickhoff, Simon B

2015-03-01

Recent evidence suggests considerable overlap between the default mode network (DMN) and regions involved in social, affective and introspective processes. We considered these overlapping regions as the social-affective part of the DMN. In this study, we established a robust mapping of the underlying brain network formed by these regions and those strongly connected to them (the extended social-affective default network). We first seeded meta-analytic connectivity modeling and resting-state analyses in the meta-analytically defined DMN regions that showed statistical overlap with regions associated with social and affective processing. Consensus connectivity of each seed was subsequently delineated by a conjunction across both connectivity analyses. We then functionally characterized the ensuing regions and performed several cluster analyses. Among the identified regions, the amygdala/hippocampus formed a cluster associated with emotional processes and memory functions. The ventral striatum, anterior cingulum, subgenual cingulum and ventromedial prefrontal cortex formed a heterogeneous subgroup associated with motivation, reward and cognitive modulation of affect. Posterior cingulum/precuneus and dorsomedial prefrontal cortex were associated with mentalizing, self-reference and autobiographic information. The cluster formed by the temporo-parietal junction and anterior middle temporal sulcus/gyrus was associated with language and social cognition. Taken together, the current work highlights a robustly interconnected network that may be central to introspective, socio-affective, that is, self- and other-related mental processes.

40 CFR 63.7515 - When must I conduct subsequent performance tests, fuel analyses, or tune-ups?

Code of Federal Regulations, 2014 CFR

2014-07-01

... performance tests, fuel analyses, or tune-ups? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL..., fuel analyses, or tune-ups? (a) You must conduct all applicable performance tests according to § 63... performance tests and the associated fuel analyses within 60 days after the completion of the performance...

40 CFR 63.7515 - When must I conduct subsequent performance tests, fuel analyses, or tune-ups?

Code of Federal Regulations, 2013 CFR

2013-07-01

... performance tests, fuel analyses, or tune-ups? 63.7515 Section 63.7515 Protection of Environment ENVIRONMENTAL..., fuel analyses, or tune-ups? (a) You must conduct all applicable performance tests according to § 63... performance tests and the associated fuel analyses within 60 days after the completion of the performance...

Construction and Analysis of Functional Networks in the Gut Microbiome of Type 2 Diabetes Patients.

PubMed

Li, Lianshuo; Wang, Zicheng; He, Peng; Ma, Shining; Du, Jie; Jiang, Rui

2016-10-01

Although networks of microbial species have been widely used in the analysis of 16S rRNA sequencing data of a microbiome, the construction and analysis of a complete microbial gene network are in general problematic because of the large number of microbial genes in metagenomics studies. To overcome this limitation, we propose to map microbial genes to functional units, including KEGG orthologous groups and the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) orthologous groups, to enable the construction and analysis of a microbial functional network. We devised two statistical methods to infer pairwise relationships between microbial functional units based on a deep sequencing dataset of gut microbiome from type 2 diabetes (T2D) patients as well as healthy controls. Networks containing such functional units and their significant interactions were constructed subsequently. We conducted a variety of analyses of global properties, local properties, and functional modules in the resulting functional networks. Our data indicate that besides the observations consistent with the current knowledge, this study provides novel biological insights into the gut microbiome associated with T2D. Copyright © 2016. Production and hosting by Elsevier Ltd.

Inconsistency in the Diagnosis of Functional Heartburn: Usefulness of Prolonged Wireless pH Monitoring in Patients With Proton Pump Inhibitor Refractory Gastroesophageal Reflux Disease

PubMed Central

Penagini, Roberto; Sweis, Rami; Mauro, Aurelio; Domingues, Gerson; Vales, Andres; Sifrim, Daniel

2015-01-01

Background/Aims The diagnosis of functional heartburn is important for management, however it stands on fragile pH monitoring variables, ie, acid exposure time varies from day to day and symptoms are often few or absent. Aim of this study was to investigate consistency of the diagnosis of functional heartburn in subsequent days using prolonged wireless pH monitoring and its impact on patients’ outcome. Methods Fifty proton pump inhibitotor refractory patients (11 male, 48 years [range, 38–57 years]) with a diagnosis of functional heart-burn according to Rome III in the first 24 hours of wireless pH monitoring were reviewed. pH variables were analysed in the following 24-hour periods to determine if tracings were indicative of diagnosis of non-erosive reflux disease (either acid exposure time > 5% or normal acid exposure time and symptom index ≥ 50%). Outcome was assessed by review of hospital files and/or telephone interview. Results Fifteen out of 50 patients had a pathological acid exposure time after the first day of monitoring (10 in the second day and 5 in subsequent days), which changed their diagnosis from functional heartburn to non-erosive reflux disease. Fifty-four percent of non-erosive reflux disease vs 11% of functional heartburn patients (P < 0.003) increased the dose of proton pump inhibitors or underwent fundoplication after the pH test. Outcome was positive in 77% of non-erosive reflux disease vs 43% of functional heartburn patients (P < 0.05). Conclusions One-third of patients classified as functional heartburn at 24-hour pH-monitoring can be re-classified as non-erosive reflux disease after a more prolonged pH recording period. This observation has a positive impact on patients’ management. PMID:25843078

Exploration Medical System Technical Development

NASA Technical Reports Server (NTRS)

McGuire, K.; Middour, C.; Cerro, J.; Burba, T.; Hanson, A.; Reilly, J.; Mindock, J.

2017-01-01

The Exploration Medical Capability (ExMC) Element systems engineering goals include defining the technical system needed to implement exploration medical capabilities for Mars. This past year, scenarios captured in the medical system concept of operations laid the foundation for systems engineering technical development work. The systems engineering team analyzed scenario content to identify interactions between the medical system, crewmembers, the exploration vehicle, and the ground system. This enabled the definition of functions the medical system must provide and interfaces to crewmembers and other systems. These analyses additionally lead to the development of a conceptual medical system architecture. The work supports the ExMC community-wide understanding of the functional exploration needs to be met by the medical system, the subsequent development of medical system requirements, and the system verification and validation approach utilizing terrestrial analogs and precursor exploration missions.

Frequency-response identification of XV-15 tilt-rotor aircraft dynamics

NASA Technical Reports Server (NTRS)

Tischler, Mark B.

1987-01-01

The timely design and development of the next generation of tilt-rotor aircraft (JVX) depend heavily on the in-depth understanding of existing XV-15 dynamics and the availability of fully validated simulation models. Previous studies have considered aircraft and simulation trim characteristics, but analyses of basic flight vehicle dynamics were limited to qualitative pilot evaluation. The present study has the following objectives: documentation and evaluation of XV-15 bare-airframe dynamics; comparison of aircraft and simulation responses; and development of a validated transfer-function description of the XV-15 needed for future studies. A nonparametric frequency-response approach is used which does not depend on assumed model order or structure. Transfer-function representations are subsequently derived which fit the frequency responses in the bandwidth of greatest concern for piloted handling-qualities and control-system applications.

The Deadline Flurry Formula

NASA Astrophysics Data System (ADS)

Stoehr, F.

2017-09-01

When having to deliver work to a fixed deadline people often wait until the very last minute, in part, because they procrastinate. While procrastination has been studied extensively in the psychology literature, few direct measures of human behaviour leading up to a deadline exist. Here we use metadata from the ALMA proposal submission process over the last five years and find that collective human behaviour for submitting work before a deadline can be described spectacularly well by a simple "universal" law. We also analyse this behaviour as a function of several other factors, such as gender, age, proposal size, number of co-authors and the subsequent success of a submitted proposal.

Purification and fractionation of membranes for proteomic analyses.

PubMed

Marmagne, Anne; Salvi, Daniel; Rolland, Norbert; Ephritikhine, Geneviève; Joyard, Jacques; Barbier-Brygoo, Hélène

2006-01-01

Proteomics is a very powerful approach to link the information contained in sequenced genomes, such as Arabidopsis, to the functional knowledge provided by studies of plant cell compartments. However, membrane proteomics remains a challenge. One way to bring into view the complex mixture of proteins present in a membrane is to develop proteomic analyses based on (1) the use of highly purified membrane fractions and (2) fractionation of membrane proteins to retrieve as many proteins as possible (from the most to the less hydrophobic ones). To illustrate such strategies, we choose two types of membranes, the plasma membrane and the chloroplast envelope membranes. Both types of membranes can be prepared in a reasonable degree of purity from different types of tissues: the plasma membrane from cultured cells and the chloroplast envelope membrane from whole plants. This article is restricted to the description of methods for the preparation of highly purified and characterized plant membrane fractions and the subsequent fractionation of these membrane proteins according to simple physicochemical criteria (i.e., chloroform/methanol extraction, alkaline or saline treatments) for further analyses using modern proteomic methodologies.

Preschool negative emotionality predicts activity and connectivity of the fusiform face area and amygdala in later childhood.

PubMed

Kann, Sarah J; O'Rawe, Jonathan F; Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

2017-09-01

Negative emotionality (NE) refers to individual differences in the propensity to experience and react with negative emotions and is associated with increased risk of psychological disorder. However, research on the neural bases of NE has focused almost exclusively on amygdala activity during emotional face processing. This study broadened this framework by examining the relationship between observed NE in early childhood and subsequent neural responses to emotional faces in both the amygdala and the fusiform face area (FFA) in a late childhood/early adolescent sample. Measures of NE were obtained from children at age 3 using laboratory observations, and functional magnetic resonance imaging (fMRI) data were collected when these children were between the ages of 9 and 12 while performing a visual stimulus identity matching task with houses and emotional faces as stimuli. Multiple regression analyses revealed that higher NE at age 3 is associated with significantly greater activation in the left amygdala and left FFA but lower functional connectivity between these two regions during the face conditions. These findings suggest that those with higher early NE have subsequent alterations in both activity and connectivity within an extended network during face processing. © The Author (2017). Published by Oxford University Press.

Postconditioning with repeated mild hypoxia protects neonatal hypoxia-ischemic rats against brain damage and promotes rehabilitation of brain function.

PubMed

Deng, Qingqing; Chang, Yanqun; Cheng, Xiaomao; Luo, Xingang; Zhang, Jing; Tang, Xiaoyuan

2018-05-01

Mild hypoxia conditioning induced by repeated episodes of transient ischemia is a clinically applicable method for protecting the brain against injury after hypoxia-ischemic brain damage. To assess the effect of repeated mild hypoxia postconditioning on brain damage and long-term neural functional recovery after hypoxia-ischemic brain damage. Rats received different protocols of repeated mild hypoxia postconditioning. Seven-day-old rats with hypoxia ischemic brain damage (HIBD) from the left carotid ligation procedure plus 2 h hypoxic stress (8% O 2 at 37 °C) were further receiving repeated mild hypoxia intermittently. The gross anatomy, functional analyses, hypoxia inducible factor 1 alpha (HIF-1a) expression, and neuronal apoptosis of the rat brains were subsequently examined. Compared to the HIBD group, rats postconditioned with mild hypoxia had elevated HIF-1a expression, more Nissl-stain positive cells in their brain tissue and their brains functioned better in behavioral analyses. The recovery of the brain function may be directly linked to the inhibitory effect of HIF-1α on neuronal apoptosis. Furthermore, there were significantly less neuronal apoptosis in the hippocampal CA1 region of the rats postconditioned with mild hypoxia, which might also be related to the higher HIF-1a expression and better brain performance. Overall, these results suggested that postconditioning of neonatal rats after HIBD with mild hypoxia increased HIF-1a expression, exerted a neuroprotective effect and promoted neural functional recovery. Repeated mild hypoxia postconditioning protects neonatal rats with HIBD against brain damage and improves neural functional recovery. Our results may have clinical implications for treating infants with HIBD. Copyright © 2018 Elsevier Inc. All rights reserved.

Recovery Expectations and Long-term Prognosis of Patients With Coronary Heart Disease

PubMed Central

Barefoot, John C.; Brummett, Beverly H.; Williams, Redford B.; Siegler, Ilene C.; Helms, Michael J.; Boyle, Stephen H.; Clapp-Channing, Nancy E.; Mark, Daniel B.

2013-01-01

Background Expectations of patients regarding their prospects for recovery have been shown to predict subsequent physical and social functioning. Evidence regarding the impact of expectations on clinical outcomes is limited. Methods At the inpatient service of a tertiary care hospital, we evaluated beliefs of patients undergoing coronary angiography about their prognosis as predictors of long-term survival and 1-year functional status. Baseline assessments, including a measure of expectations for recovery, were obtained during hospitalization with mortality follow-up for approximately 15 years. Patients with significant obstructive coronary artery disease were interviewed while in the hospital and enrolled in follow-up. Functional status was assessed at baseline and 1 year later with questionnaires reflecting physical capabilities. Analyses controlled for age, sex, disease severity, comorbidities, treatments, demographics, depressive symptoms, social support, and functional status. There were 1637 total deaths, 885 from cardiovascular causes, in the 2818 patients in these analyses. The outcomes were total mortality, cardiovascular mortality, and 1-year functional status. Results Expectations were positively associated with survival after controlling for background and clinical disease indicators. For a difference equivalent to an inter-quartile range of expectations, the hazard ratio (HR) for total mortality was 0.76 (95% confidence interval [CI], 0.71–0.82) and 0.76 (95% CI, 0.69–0.83) for cardiovascular mortality. The HRs were 0.83 (95% CI, 0.76–0.91) and 0.79 (95% CI, 0.70–0.89) with further adjustments for demographic and psychosocial covariates. Similar associations (P<.001) were observed for functional status. Conclusion Recovery expectations at baseline were positively associated with long-term survival and functioning in patients with coronary artery disease. PMID:21357800

Pre-fracture nutritional status is predictive of functional status at discharge during the acute phase with hip fracture patients: A multicenter prospective cohort study.

PubMed

Inoue, Tatsuro; Misu, Syogo; Tanaka, Toshiaki; Sakamoto, Hiroki; Iwata, Kentaro; Chuman, Yuki; Ono, Rei

2017-10-01

Malnutrition is common in patients with hip fractures, and elderly patients with hip fractures lose functional independence and often fail to recover previous functional status. The aim of this study was to determine whether pre-fracture nutritional status predicts functional status of patients with hip fracture at discharge from acute hospitals. In the present multicenter prospective cohort study, pre-fracture nutritional status was assessed using the Mini Nutritional Assessment Short-Form (MNA-SF). At discharge from acute hospitals, functional status was evaluated using a functional independent measurement instrument (FIM). Subsequently, multiple regression analyses were performed using FIM as the dependent variable and MNA-SF as the independent variable. Among the 204 patients analyzed in the present study, the mean length of hospital stay was 26.2 ± 12.6 days, and according to MNA-SF assessments, 51 (25.0%) patients were malnourished, 98 (48.0%) were at risk of malnutrition, and 55 (27.0%) were well-nourished before fracture. At discharge, FIM scores were higher in patients who were well-nourished than in those who were malnourished or were at risk of malnutrition (p < 0.01). After adjustment for confounding factors, multiple regression analyses showed that MNA-SF was a significant independent predictor for FIM at discharge (well-nourished vs. malnourished, β = -0.86, p < 0.01). Pre-fracture nutritional status was a significant independent predictor for functional status at discharge during the acute phase, warranting early assessment of nutritional status and early intervention for successful postoperative rehabilitation. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Recovery expectations and long-term prognosis of patients with coronary heart disease.

PubMed

Barefoot, John C; Brummett, Beverly H; Williams, Redford B; Siegler, Ilene C; Helms, Michael J; Boyle, Stephen H; Clapp-Channing, Nancy E; Mark, Daniel B

2011-05-23

Expectations of patients regarding their prospects for recovery have been shown to predict subsequent physical and social functioning. Evidence regarding the impact of expectations on clinical outcomes is limited. At the inpatient service of a tertiary care hospital, we evaluated beliefs of patients undergoing coronary angiography about their prognosis as predictors of long-term survival and 1-year functional status. Baseline assessments, including a measure of expectations for recovery, were obtained during hospitalization with mortality follow-up for approximately 15 years. Patients with significant obstructive coronary artery disease were interviewed while in the hospital and enrolled in follow-up. Functional status was assessed at baseline and 1 year later with questionnaires reflecting physical capabilities. Analyses controlled for age, sex, disease severity, comorbidities, treatments, demographics, depressive symptoms, social support, and functional status. There were 1637 total deaths, 885 from cardiovascular causes, in the 2818 patients in these analyses. The outcomes were total mortality, cardiovascular mortality, and 1-year functional status. Expectations were positively associated with survival after controlling for background and clinical disease indicators. For a difference equivalent to an interquartile range of expectations, the hazard ratio (HR) for total mortality was 0.76 (95% confidence interval [CI], 0.71-0.82) and 0.76 (95% CI, 0.69-0.83) for cardiovascular mortality. The HRs were 0.83 (95% CI, 0.76-0.91) and 0.79 (95% CI, 0.70-0.89) with further adjustments for demographic and psychosocial covariates. Similar associations (P < .001) were observed for functional status. Recovery expectations at baseline were positively associated with long-term survival and functioning in patients with coronary artery disease.

Biphasic decline in renal function after radical cystectomy with urinary diversion.

PubMed

Makino, Katsuhiro; Nakagawa, Tohru; Kanatani, Atsushi; Kawai, Taketo; Taguchi, Satoru; Otsuka, Masafumi; Matsumoto, Akihiko; Miyazaki, Hideyo; Fujimura, Tetsuya; Fukuhara, Hiroshi; Kume, Haruki; Homma, Yukio

2017-04-01

We evaluated short- and long-term renal function in patients after radical cystectomy with urinary diversion and identified risk factors for the deterioration of renal function. This retrospective study comprised 91 patients who underwent radical cystectomy and urinary diversion for bladder cancer and survived ≥3 years after surgery. The estimated glomerular filtration rate (eGFR) was calculated, and longitudinal changes of eGFR were assessed. Deterioration in renal function in early and late postoperative years was defined as a ≥25 % decrease in the eGFR from preoperative to postoperative year one, and a reduction in the eGFR of >1 mL/min/1.73 m 2 annually in subsequent years, respectively. Univariate and multivariate logistic regression analyses were used to evaluate its association with clinicopathologic features. The median follow-up period after surgery was 7 years (range 3-26). The mean eGFR decreased from preoperative 65.1 to 58.9 mL/min/1.73 m 2 1 year after the surgery, followed by a continuous decline of ~1.0 mL/min/1.73 m 2 per year thereafter. Multivariate analyses identified ureteroenteric stricture as the sole risk factor associated with early renal function deterioration [odds ratio (OR) 4.22, p = 0.037]. Diabetes mellitus (OR 8.24, p = 0.015) and episodes of pyelonephritis (OR 4.89, p = 0.038) were independently associated with the gradual decline in the late postoperative period. In cystectomy patients with urinary diversion, the rapid deterioration of renal function observed during the first year after surgery and the gradual but continuous decline in function thereafter were found to be associated with different risk factors.

A vertical-energy-thresholding procedure for data reduction with multiple complex curves.

PubMed

Jung, Uk; Jeong, Myong K; Lu, Jye-Chyi

2006-10-01

Due to the development of sensing and computer technology, measurements of many process variables are available in current manufacturing processes. It is very challenging, however, to process a large amount of information in a limited time in order to make decisions about the health of the processes and products. This paper develops a "preprocessing" procedure for multiple sets of complicated functional data in order to reduce the data size for supporting timely decision analyses. The data type studied has been used for fault detection, root-cause analysis, and quality improvement in such engineering applications as automobile and semiconductor manufacturing and nanomachining processes. The proposed vertical-energy-thresholding (VET) procedure balances the reconstruction error against data-reduction efficiency so that it is effective in capturing key patterns in the multiple data signals. The selected wavelet coefficients are treated as the "reduced-size" data in subsequent analyses for decision making. This enhances the ability of the existing statistical and machine-learning procedures to handle high-dimensional functional data. A few real-life examples demonstrate the effectiveness of our proposed procedure compared to several ad hoc techniques extended from single-curve-based data modeling and denoising procedures.

Validity of self-reported stroke in elderly African Americans, Caribbean Hispanics, and Whites.

PubMed

Reitz, Christiane; Schupf, Nicole; Luchsinger, José A; Brickman, Adam M; Manly, Jennifer J; Andrews, Howard; Tang, Ming X; DeCarli, Charles; Brown, Truman R; Mayeux, Richard

2009-07-01

The validity of a self-reported stroke remains inconclusive. To validate the diagnosis of self-reported stroke using stroke identified by magnetic resonance imaging (MRI) as the standard. Community-based cohort study of nondemented, ethnically diverse elderly persons in northern Manhattan. High-resolution quantitative MRIs were acquired for 717 participants without dementia. Sensitivity and specificity of stroke by self-report were examined using cross-sectional analyses and the chi(2) test. Putative relationships between factors potentially influencing the reporting of stroke, including memory performance, cognitive function, and vascular risk factors, were assessed using logistic regression models. Subsequently, all analyses were repeated, stratified by age, sex, ethnic group, and level of education. In analyses of the whole sample, sensitivity of stroke self-report for a diagnosis of stroke on MRI was 32.4%, and specificity was 78.9%. In analyses stratified by median age (80.1 years), the validity between reported stroke and detection of stroke on MRI was significantly better in the younger than the older age group (for all vascular territories: sensitivity and specificity, 36.7% and 81.3% vs 27.6% and 26.2%; P = .02). Impaired memory, cognitive skills, or language ability and the presence of hypertension or myocardial infarction were associated with higher rates of false-negative results. Using brain MRI as the standard, specificity and sensitivity of stroke self-report are low. Accuracy of self-report is influenced by age, presence of vascular disease, and cognitive function. In stroke research, sensitive neuroimaging techniques rather than stroke self-report should be used to determine stroke history.

Statistical limitations in functional neuroimaging. I. Non-inferential methods and statistical models.

PubMed Central

Petersson, K M; Nichols, T E; Poline, J B; Holmes, A P

1999-01-01

Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference. PMID:10466149

Gastrointestinal symptoms predictors of health-related quality of life in pediatric patients with functional gastrointestinal disorders.

PubMed

Varni, James W; Shulman, Robert J; Self, Mariella M; Nurko, Samuel; Saps, Miguel; Saeed, Shehzad A; Patel, Ashish S; Dark, Chelsea Vaughan; Bendo, Cristiane B; Pohl, John F

2017-04-01

To investigate the patient-reported multidimensional gastrointestinal symptoms predictors of generic health-related quality of life (HRQOL) in pediatric patients with functional gastrointestinal disorders (FGIDs). The Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and PedsQL™ 4.0 Generic Core Scales were completed in a 9-site study by 259 pediatric patients with functional constipation, functional abdominal pain (FAP), or irritable bowel syndrome (IBS). Gastrointestinal Symptoms Scales measuring stomach pain, stomach discomfort when eating, food and drink limits, trouble swallowing, heartburn and reflux, nausea and vomiting, gas and bloating, constipation, blood in poop, and diarrhea were identified as clinically important symptom differentiators from healthy controls based on prior findings, and subsequently tested for bivariate and multivariate linear associations with overall HRQOL. Gastrointestinal symptoms were differentially associated with decreased HRQOL in bivariate analyses for the three FGIDs. In predictive models utilizing hierarchical multiple regression analyses controlling for age, gender, and race/ethnicity, gastrointestinal symptoms differentially accounted for an additional 47, 40, and 60 % of the variance in patient-reported HRQOL for functional constipation, FAP, and IBS, respectively, reflecting large effect sizes. Significant individual gastrointestinal symptoms predictors were identified after controlling for the other gastrointestinal symptoms in the FGID-specific predictive models. Gastrointestinal symptoms represent potentially modifiable predictors of generic HRQOL in pediatric patients with FGIDs. Identifying the condition-specific gastrointestinal symptoms that are the most important predictors from the patient perspective facilitates a patient-centered approach to targeted interventions designed to ameliorate impaired overall HRQOL.

Evolution and function of eukaryotic-like proteins from sponge symbionts.

PubMed

Reynolds, David; Thomas, Torsten

2016-10-01

Sponges (Porifera) are ancient metazoans that harbour diverse microorganisms, whose symbiotic interactions are essential for the host's health and function. Although symbiosis between bacteria and sponges are ubiquitous, the molecular mechanisms that control these associations are largely unknown. Recent (meta-) genomic analyses discovered an abundance of genes encoding for eukaryotic-like proteins (ELPs) in bacterial symbionts from different sponge species. ELPs belonging to the ankyrin repeat (AR) class from a bacterial symbiont of the sponge Cymbastela concentrica were subsequently found to modulate amoebal phagocytosis. This might be a molecular mechanism, by which symbionts can control their interaction with the sponge. In this study, we investigated the evolution and function of ELPs from other classes and from symbionts found in other sponges to better understand the importance of ELPs for bacteria-eukaryote interactions. Phylogenetic analyses showed that all of the nine ELPs investigated were most closely related to proteins found either in eukaryotes or in bacteria that can live in association with eukaryotes. ELPs were then recombinantly expressed in Escherichia coli and exposed to the amoeba Acanthamoeba castellanii, which is functionally analogous to phagocytic cells in sponges. Phagocytosis assays with E. coli containing three ELP classes (AR, TPR-SEL1 and NHL) showed a significantly higher percentage of amoeba containing bacteria and average number of intracellular bacteria per amoeba when compared to negative controls. The result that various classes of ELPs found in symbionts of different sponges can modulate phagocytosis indicates that they have a broader function in mediating bacteria-sponge interactions. © 2016 John Wiley & Sons Ltd.

Executive Function Processes Predict Mobility Outcomes in Older Adults

PubMed Central

Gothe, Neha P.; Fanning, Jason; Awick, Elizabeth; Chung, David; Wójcicki, Thomas R.; Olson, Erin A.; Mullen, Sean P.; Voss, Michelle; Erickson, Kirk I.; Kramer, Arthur F.; McAuley, Edward

2013-01-01

BACKGROUND: There is growing evidence suggesting an association between cognitive function and physical performance in late life. This study examined the relationship between performance on executive function measures and subsequent mobility outcomes among community dwelling older adults across a 12-month randomized controlled exercise trial. DESIGN: Randomized controlled clinical trial SETTING: Champaign-Urbana, Illinois PARTICIPANTS: Community dwelling older adults (N = 179; Mage = 66.4) INTERVENTION: A 12-month exercise trial with two arms: an aerobic exercise group and a stretching and strengthening group MEASUREMENTS: Established cognitive tests of executive function including the flanker task, task switching and a dual task paradigm, and the Wisconsin card sort test. Mobility was assessed using the timed 8-foot up and go test and times to climb up and down a flight of stairs. METHODS: Participants completed the cognitive measures at baseline and the mobility measures at baseline and after 12 months of the intervention. Multiple regression analyses were conducted to determine whether baseline executive function predicted post-intervention functional performance after controlling for age, sex, education, cardiorespiratory fitness and baseline mobility levels. RESULTS: Our analyses revealed that selective baseline executive function measures, particularly performance on the flanker task (β’s =.15 to .17) and the Wisconsin card sort test (β’s =.11 to .16) consistently predicted mobility outcomes at month 12. The estimates were in the expected direction, such that better baseline performance on the executive function measures predicted better performance on the timed mobility tests independent of the intervention group. CONCLUSION: Executive functions of inhibitory control, mental set shifting and attentional flexibility were predictive of functional mobility. Given the literature associating mobility limitations with disability, morbidity, and mortality, these results are important for understanding the antecedents to poor mobility function that can be attenuated by well-designed interventions to improve cognitive performance. PMID:24521364

Assessment of protein set coherence using functional annotations

PubMed Central

Chagoyen, Monica; Carazo, Jose M; Pascual-Montano, Alberto

2008-01-01

Background Analysis of large-scale experimental datasets frequently produces one or more sets of proteins that are subsequently mined for functional interpretation and validation. To this end, a number of computational methods have been devised that rely on the analysis of functional annotations. Although current methods provide valuable information (e.g. significantly enriched annotations, pairwise functional similarities), they do not specifically measure the degree of homogeneity of a protein set. Results In this work we present a method that scores the degree of functional homogeneity, or coherence, of a set of proteins on the basis of the global similarity of their functional annotations. The method uses statistical hypothesis testing to assess the significance of the set in the context of the functional space of a reference set. As such, it can be used as a first step in the validation of sets expected to be homogeneous prior to further functional interpretation. Conclusion We evaluate our method by analysing known biologically relevant sets as well as random ones. The known relevant sets comprise macromolecular complexes, cellular components and pathways described for Saccharomyces cerevisiae, which are mostly significantly coherent. Finally, we illustrate the usefulness of our approach for validating 'functional modules' obtained from computational analysis of protein-protein interaction networks. Matlab code and supplementary data are available at PMID:18937846

Photogenerated Lectin Sensors Produced by Thiol-Ene/Yne Photo-Click Chemistry in Aqueous Solution

PubMed Central

Norberg, Oscar; Lee, Irene H.; Aastrup, Teodor; Yan, Mingdi; Ramström, Olof

2012-01-01

The photoinitiated radical reactions between thiols and alkenes/alkynes (thiol-ene and thiol-yne chemistry) have been applied to a functionalization methodology to produce carbohydrate-presenting surfaces for analyses of biomolecular interactions. Polymer-coated quartz surfaces were functionalized with alkenes or alkynes in a straightforward photochemical procedure utilizing perfluorophenylazide (PFPA) chemistry. The alkene/alkyne surfaces were subsequently allowed to react with carbohydrate thiols in water under UV-irradiation. The reaction can be carried out in a drop of water directly on the surface without photoinitiator and any disulfide side products were easily washed away after the functionalization process. The resulting carbohydrate-presenting surfaces were evaluated in real-time studies of protein-carbohydrate interactions using a quartz crystal microbalance flow-through system with recurring injections of selected lectins with intermediate regeneration steps using low pH buffer. The resulting methodology proved fast, efficient and scalable to high-throughput analysis formats, and the produced surfaces showed significant protein binding with expected selectivities of the lectins used in the study. PMID:22341757

Phylogenomic evolutionary surveys of subtilase superfamily genes in fungi.

PubMed

Li, Juan; Gu, Fei; Wu, Runian; Yang, JinKui; Zhang, Ke-Qin

2017-03-30

Subtilases belong to a superfamily of serine proteases which are ubiquitous in fungi and are suspected to have developed distinct functional properties to help fungi adapt to different ecological niches. In this study, we conducted a large-scale phylogenomic survey of subtilase protease genes in 83 whole genome sequenced fungal species in order to identify the evolutionary patterns and subsequent functional divergences of different subtilase families among the main lineages of the fungal kingdom. Our comparative genomic analyses of the subtilase superfamily indicated that extensive gene duplications, losses and functional diversifications have occurred in fungi, and that the four families of subtilase enzymes in fungi, including proteinase K-like, Pyrolisin, kexin and S53, have distinct evolutionary histories which may have facilitated the adaptation of fungi to a broad array of life strategies. Our study provides new insights into the evolution of the subtilase superfamily in fungi and expands our understanding of the evolution of fungi with different lifestyles.

Cognitive function and competitive employment in schizophrenia: relative contribution of insight and psychopathology.

PubMed

Giugiario, Michela; Crivelli, Barbara; Mingrone, Cinzia; Montemagni, Cristiana; Scalese, Mara; Sigaudo, Monica; Rocca, Giuseppe; Rocca, Paola

2012-04-01

This study investigated the relationships among insight, psychopathology, cognitive function, and competitive employment in order to determine whether insight and/or psychopathology carried the influence of cognitive function to competitive employment. We recruited 253 outpatients with stable schizophrenia and we further divided our sample into two groups of patients (unemployed and competitive employment subjects). Clinical and neuropsychological assessments were performed. All clinical variables significantly different between the two groups of subjects were subsequently analyzed using a binary logistic regression to assess their independent contribution to competitive employment in the two patients' groups. On the basis of the regression results two mediation analyses were performed. Verbal memory, general psychopathology, and awareness of mental illness were significantly associated with competitive employment in our sample. Both awareness of mental illness and general psychopathology had a role in mediating the verbal memory-competitive employment relationship. Taken together, these findings confirmed the importance of cognitive function in obtaining competitive employment. Our results also highlighted the independent role of general psychopathology and awareness of illness on occupational functioning in schizophrenia. Thus, a greater attention must be given to the systematic investigation of insight and general psychopathology in light of an amelioration of vocational functioning in stable schizophrenia.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex

PubMed Central

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.

2017-01-01

Abstract Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. PMID:28402565

Identification of novel candidate genes involved in mineralization of dental enamel by genome-wide transcript profiling.

PubMed

Lacruz, Rodrigo S; Smith, Charles E; Bringas, Pablo; Chen, Yi-Bu; Smith, Susan M; Snead, Malcolm L; Kurtz, Ira; Hacia, Joseph G; Hubbard, Michael J; Paine, Michael L

2012-05-01

The gene repertoire regulating vertebrate biomineralization is poorly understood. Dental enamel, the most highly mineralized tissue in mammals, differs from other calcifying systems in that the formative cells (ameloblasts) lack remodeling activity and largely degrade and resorb the initial extracellular matrix. Enamel mineralization requires that ameloblasts undergo a profound functional switch from matrix-secreting to maturational (calcium transport, protein resorption) roles as mineralization progresses. During the maturation stage, extracellular pH decreases markedly, placing high demands on ameloblasts to regulate acidic environments present around the growing hydroxyapatite crystals. To identify the genetic events driving enamel mineralization, we conducted genome-wide transcript profiling of the developing enamel organ from rat incisors and highlight over 300 genes differentially expressed during maturation. Using multiple bioinformatics analyses, we identified groups of maturation-associated genes whose functions are linked to key mineralization processes including pH regulation, calcium handling, and matrix turnover. Subsequent qPCR and Western blot analyses revealed that a number of solute carrier (SLC) gene family members were up-regulated during maturation, including the novel protein Slc24a4 involved in calcium handling as well as other proteins of similar function (Stim1). By providing the first global overview of the cellular machinery required for enamel maturation, this study provide a strong foundation for improving basic understanding of biomineralization and its practical applications in healthcare. Copyright © 2011 Wiley Periodicals, Inc.

Morphometric analysis of sex differences in contemporary Japanese pelves using multidetector computed tomography.

PubMed

Torimitsu, Suguru; Makino, Yohsuke; Saitoh, Hisako; Sakuma, Ayaka; Ishii, Namiko; Yajima, Daisuke; Inokuchi, Go; Motomura, Ayumi; Chiba, Fumiko; Yamaguchi, Rutsuko; Hashimoto, Mari; Hoshioka, Yumi; Iwase, Hirotaro

2015-12-01

Sex estimation of decomposed or skeletal remains is clearly important in forensic contexts. Recently, contemporary population-specific data has been obtained using multidetector computed tomography (MDCT) scanning. The main purpose of this study was to investigate skeletal pelvic dimorphism in a contemporary Japanese forensic sample and to quantify the accuracy of sex estimation using various pelvic measurements obtained from three-dimensional (3D) CT images. This study used a total of 208 cadavers (104 males, 104 females) of which postmortem CT scanning and subsequent forensic autopsy were conducted between December 2011 and August 2014. Eleven measurements of each pelvis were obtained from 3D CT reconstructed images that extracted only bone data. The measurements were analyzed using descriptive statistics and discriminant function analyses. All except one measurement were dimorphic in terms of sex differences. Univariate discriminant function analyses using these measurements provided sex classification accuracy rates of 62.0-98.1%. The subpubic angle was found to contribute most significantly to accurate sex estimation. Multivariate discriminant functions yielded sex prediction accuracy rates of 63.9-98.1%. In conclusion, the pelvic measurements obtained from 3D CT images of a contemporary Japanese population successfully demonstrated sexual dimorphism and may be useful for the estimation of skeletal sex in the field of forensic anthropology. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The plant leaf movement analyzer (PALMA): a simple tool for the analysis of periodic cotyledon and leaf movement in Arabidopsis thaliana.

PubMed

Wagner, Lucas; Schmal, Christoph; Staiger, Dorothee; Danisman, Selahattin

2017-01-01

The analysis of circadian leaf movement rhythms is a simple yet effective method to study effects of treatments or gene mutations on the circadian clock of plants. Currently, leaf movements are analysed using time lapse photography and subsequent bioinformatics analyses of leaf movements. Programs that are used for this purpose either are able to perform one function (i.e. leaf tip detection or rhythm analysis) or their function is limited to specific computational environments. We developed a leaf movement analysis tool-PALMA-that works in command line and combines image extraction with rhythm analysis using Fast Fourier transformation and non-linear least squares fitting. We validated PALMA in both simulated time series and in experiments using the known short period mutant sensitivity to red light reduced 1 ( srr1 - 1 ). We compared PALMA with two established leaf movement analysis tools and found it to perform equally well. Finally, we tested the effect of reduced iron conditions on the leaf movement rhythms of wild type plants. Here, we found that PALMA successfully detected period lengthening under reduced iron conditions. PALMA correctly estimated the period of both simulated and real-life leaf movement experiments. As a platform-independent console-program that unites both functions needed for the analysis of circadian leaf movements it is a valid alternative to existing leaf movement analysis tools.

Novel functions for glycosyltransferases Jhp0562 and GalT in Lewis antigen synthesis and variation in Helicobacter pylori.

PubMed

Pohl, Mary Ann; Kienesberger, Sabine; Blaser, Martin J

2012-04-01

Lewis (Le) antigens are fucosylated oligosaccharides present in the Helicobacter pylori lipopolysaccharide. Expression of these antigens is believed to be important for H. pylori colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galT is essential for production of type 1 (Le(a) and Le(b)) antigens. The upstream gene jhp0562, which is present in many but not all H. pylori strains, is homologous to β-(1,3)galT but is of unknown function. Because H. pylori demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5' and 3' ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galT null mutant, but neither native nor recombinant jhp0562 can. Mutagenesis of jhp0562 revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galT expression in all wild-type (WT) and mutant strains tested, whereas jhp0562 was not expressed in jhp0562 null mutants, as expected. Since jhp0562 unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether galT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that galT is essential for Le(b) production. In total, these results demonstrate that galT and jhp0562 have functions that cross the expected Le synthesis pathways and that jhp0562 provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes.

Novel Functions for Glycosyltransferases Jhp0562 and GalT in Lewis Antigen Synthesis and Variation in Helicobacter pylori

PubMed Central

Kienesberger, Sabine; Blaser, Martin J.

2012-01-01

Lewis (Le) antigens are fucosylated oligosaccharides present in the Helicobacter pylori lipopolysaccharide. Expression of these antigens is believed to be important for H. pylori colonization, since Le antigens also are expressed on the gastric epithelia in humans. A galactosyltransferase encoded by β-(1,3)galT is essential for production of type 1 (Lea and Leb) antigens. The upstream gene jhp0562, which is present in many but not all H. pylori strains, is homologous to β-(1,3)galT but is of unknown function. Because H. pylori demonstrates extensive intragenomic recombination, we hypothesized that these two genes could undergo DNA rearrangement. A PCR screen and subsequent sequence analyses revealed that the two genes can recombine at both the 5′ and 3′ ends. Chimeric β-(1,3)galT-like alleles can restore function in a β-(1,3)galT null mutant, but neither native nor recombinant jhp0562 can. Mutagenesis of jhp0562 revealed that it is essential for synthesis of both type 1 and type 2 Le antigens. Transcriptional analyses of both loci showed β-(1,3)galT expression in all wild-type (WT) and mutant strains tested, whereas jhp0562 was not expressed in jhp0562 null mutants, as expected. Since jhp0562 unexpectedly displayed functions in both type 1 and type 2 Le synthesis, we asked whether galT, part of the type 2 synthesis pathway, had analogous functions in type 1 synthesis. Mutagenesis and complementation analysis confirmed that galT is essential for Leb production. In total, these results demonstrate that galT and jhp0562 have functions that cross the expected Le synthesis pathways and that jhp0562 provides a substrate for intragenomic recombination to generate diverse Le synthesis enzymes. PMID:22290141

The ankle brachial index and change in lower extremity functioning over time: the Women's Health and Aging Study.

PubMed

McDermott, Mary McGrae; Ferrucci, Luigi; Simonsick, Eleanor M; Balfour, Jennifer; Fried, Linda; Ling, Shari; Gibson, Daniel; Guralnik, Jack M

2002-02-01

To define the association between baseline ankle brachial index (ABI) level and subsequent onset of severe disability. Prospective cohort study. Baltimore community. Eight hundred forty-seven disabled women aged 65 and older participating in the Women's Health and Aging Study. At baseline, participants underwent measurement of ABI and lower extremity functioning. Measures of lower extremity functioning included patient's report of their ability to walk one-quarter of a mile, number of city blocks walked last week, number of stair flights climbed last week, and performance-based measures including walking speed over 4 meters, five repeated chair stands, and a summary performance score. Functioning was remeasured every 6 months for 3 years. Definitions of severe disability were developed a priori, and participants who met these definitions at baseline were excluded from subsequent analyses. Participants with an ABI of less than 0.60 at baseline had significantly higher cumulative probabilities of developing severe disability than participants with a baseline ABI of 0.90 to 1.50 for walking-specific outcomes (ability to walk a quarter of a mile, number of city blocks walked last week, and walking velocity) but not for the remaining functional outcomes. In age-adjusted Cox proportional hazards analyses, hazard ratios for participants with a baseline ABI of less than 0.60 were 1.63 for becoming unable to walk a quarter of a mile (P = .044), 2.00 for developing severe disability in the number of blocks walked last week (P = .004), and 1.61 for developing severe disability in walking speed (P = .041), compared with participants with a baseline ABI of 0.90 to 1.50. Adjusting for age, race, baseline performance, and comorbidities, an ABI of less than 0.60 remained associated with becoming severely disabled in the number of blocks walked last week (hazard ratio = 1.97, P = .009) and nearly significantly associated with becoming unable to walk a quarter of a mile (hazard ratio = 1.54, P = .09). In fully adjusted random effects models, a baseline ABI of less than 0.60 was associated with significantly greater decline in walking speed per year (P = .019) and nearly significantly greater decline in number of blocks walked last week per year (P = .053) compared with a baseline ABI of 0.90 to 1.50. In community-dwelling disabled older women, a low ABI is associated with a greater incidence of severe disability in walking-specific but not other lower extremity functional outcomes, compared with persons with a normal ABI over 3 years.

Spaceflight payload design flight experience G-408

NASA Technical Reports Server (NTRS)

Durgin, William W.; Looft, Fred J.; Sacco, Albert, Jr.; Thompson, Robert; Dixon, Anthony G.; Roberti, Dino; Labonte, Robert; Moschini, Larry

1992-01-01

Worcester Polytechnic Institute's first payload of spaceflight experiments flew aboard Columbia, STS-40, during June of 1991 and culminated eight years of work by students and faculty. The Get Away Special (GAS) payload was installed on the GAS bridge assembly at the aft end of the cargo bay behind the Spacelab Life Sciences (SLS-1) laboratory. The Experiments were turned on by astronaut signal after reaching orbit and then functioned for 72 hours. Environmental and experimental measurements were recorded on three cassette tapes which, together with zeolite crystals grown on orbit, formed the basis of subsequent analyses. The experiments were developed over a number of years by undergraduate students meeting their project requirements for graduation. The experiments included zeolite crystal growth, fluid behavior, and microgravity acceleration measurement in addition to environmental data acquisition. Preparation also included structural design, thermal design, payload integration, and experiment control. All of the experiments functioned on orbit and the payload system performed within design estimates.

Prospect evaluation as a function of numeracy and probability denominator.

PubMed

Millroth, Philip; Juslin, Peter

2015-05-01

This study examines how numeracy and probability denominator (a direct-ratio probability, a relative frequency with denominator 100, a relative frequency with denominator 10,000) affect the evaluation of prospects in an expected-value based pricing task. We expected that numeracy would affect the results due to differences in the linearity of number perception and the susceptibility to denominator neglect with different probability formats. An analysis with functional measurement verified that participants integrated value and probability into an expected value. However, a significant interaction between numeracy and probability format and subsequent analyses of the parameters of cumulative prospect theory showed that the manipulation of probability denominator changed participants' psychophysical response to probability and value. Standard methods in decision research may thus confound people's genuine risk attitude with their numerical capacities and the probability format used. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipids: From Chemical Structures, Biosynthesis, and Analyses to Industrial Applications.

PubMed

Li-Beisson, Yonghua; Nakamura, Yuki; Harwood, John

2016-01-01

Lipids are one of the major subcellular components, and play numerous essential functions. As well as their physiological roles, oils stored in biomass are useful commodities for a variety of biotechnological applications including food, chemical feedstocks, and fuel. Due to their agronomic as well as economic and societal importance, lipids have historically been subjected to intensive studies. Major current efforts are to increase the energy density of cell biomass, and/or create designer oils suitable for specific applications. This chapter covers some basic aspects of what one needs to know about lipids: definition, structure, function, metabolism and focus is also given on the development of modern lipid analytical tools and major current engineering approaches for biotechnological applications. This introductory chapter is intended to serve as a primer for all subsequent chapters in this book outlining current development in specific areas of lipids and their metabolism.

Compensatory Hypertrophy Induced by Ventricular Cardiomyocyte Specific COX-2 Expression in Mice

PubMed Central

Streicher, John M.; Kamei, Kenichiro; Ishikawa, Tomo-o; Herschman, Harvey; Wang, Yibin

2010-01-01

Cyclooxygenase-2 (COX-2) is an important mediator of inflammation in stress and disease states. Recent attention has focused on the role of COX-2 in human heart failure and diseases, due to the finding that highly specific COX-2 inhibitors (i.e. Vioxx) increased the risk of myocardial infarction and stroke in chronic users. However, the specific impact of COX-2 expression in the intact heart remains to be determined. We report here the development of a transgenic mouse model, using a loxP-Cre approach, that displays robust COX-2 overexpression and subsequent prostaglandin synthesis specifically in ventricular myocytes. Histological, functional and molecular analyses showed that ventricular myocyte specific COX-2 overexpression led to cardiac hypertrophy and fetal gene marker activation, but with preserved cardiac function. Therefore, specific induction of COX-2 and prostaglandin in vivo is sufficient to induce compensated hypertrophy and molecular remodeling. PMID:20170663

BIOCHEM-ORCHESTRA: a tool for evaluating chemical speciation and ecotoxicological impacts of heavy metals on river flood plain systems.

PubMed

Vink, J P M; Meeussen, J C L

2007-08-01

The chemical speciation model BIOCHEM was extended with ecotoxicological transfer functions for uptake of metals (As, Cd, Cu, Ni, Pb, and Zn) by plants and soil invertebrates. It was coupled to the object-oriented framework ORCHESTRA to achieve a flexible and dynamic decision support system (DSS) to analyse natural or anthropogenic changes that occur in river systems. The DSS uses the chemical characteristics of soils and sediments as input, and calculates speciation and subsequent uptake by biota at various scenarios. Biotic transfer functions were field-validated, and actual hydrological conditions were derived from long-term monitoring data. The DSS was tested for several scenarios that occur in the Meuse catchment areas, such as flooding and sedimentation of riverine sediments on flood plains. Risks are expressed in terms of changes in chemical mobility, and uptake by flood plain key species (flora and fauna).

Biomechanical Analysis of the Efficacy of Locking Plates during Cyclic Loading in Metacarpal Fractures

PubMed Central

Meffert, Rainer H.; Raschke, Michael J.; Blunk, Torsten; Ochman, Sabine

2014-01-01

Purpose. To analyse the biomechanical characteristics of locking plates under cyclic loading compared to a nonlocking plate in a diaphyseal metacarpal fracture. Methods. Oblique diaphyseal shaft fractures in porcine metacarpal bones were created in a biomechanical fracture model. An anatomical reduction and stabilization with a nonlocking and a comparable locking plate in mono- or bicortical screw fixation followed. Under cyclic loading, the displacement, and in subsequent load-to-failure tests, the maximum load and stiffness were measured. Results. For the monocortical screw fixation of the locking plate, a similar displacement, maximum load, and stiffness could be demonstrated compared to the bicortical screw fixation of the nonlocking plate. Conclusions. Locking plates in monocortical configuration may function as a useful alternative to the currently common treatment with bicortical fixations. Thereby, irritation of the flexor tendons would be avoided without compromising the stability, thus enabling the necessary early functional rehabilitation. PMID:24757429

Density functional theory for hard uniaxial particles: Complex ordering of pear-shaped and spheroidal particles near a substrate

NASA Astrophysics Data System (ADS)

Schönhöfer, Philipp W. A.; Schröder-Turk, Gerd E.; Marechal, Matthieu

2018-03-01

We develop a density functional for hard particles with a smooth uniaxial shape (including non-inversion-symmetric particles) within the framework of fundamental measure theory. By applying it to a system of tapered, aspherical liquid-crystal formers, reminiscent of pears, we analyse their behaviour near a hard substrate. The theory predicts a complex orientational ordering close to the substrate, which can be directly related to the particle shape, in good agreement with our simulation results. Furthermore, the lack of particle inversion-symmetry implies the possibility of alternating orientations in subsequent layers as found in a smectic/lamellar phase of such particles. Both theory and Monte Carlo simulations confirm that such ordering occurs in our system. Our results are relevant for adsorption processes of asymmetric colloidal particles and molecules at hard interfaces and show once again that tapering strongly affects the properties of orientationally ordered phases.

A Rasch Analysis of Assessments of Morning and Evening Fatigue in Oncology Patients Using the Lee Fatigue Scale.

PubMed

Lerdal, Anners; Kottorp, Anders; Gay, Caryl; Aouizerat, Bradley E; Lee, Kathryn A; Miaskowski, Christine

2016-06-01

To accurately investigate diurnal variations in fatigue, a measure needs to be psychometrically sound and demonstrate stable item function in relationship to time of day. Rasch analysis is a modern psychometric approach that can be used to evaluate these characteristics. To evaluate, using Rasch analysis, the psychometric properties of the Lee Fatigue Scale (LFS) in a sample of oncology patients. The sample comprised 587 patients (mean age 57.3 ± 11.9 years, 80% women) undergoing chemotherapy for breast, gastrointestinal, gynecological, or lung cancer. Patients completed the 13-item LFS within 30 minutes of awakening (i.e., morning fatigue) and before going to bed (i.e., evening fatigue). Rasch analysis was used to assess validity and reliability. In initial analyses of differential item function, eight of the 13 items functioned differently depending on whether the LFS was completed in the morning or in the evening. Subsequent analyses were conducted separately for the morning and evening fatigue assessments. Nine of the morning fatigue items and 10 of the evening fatigue items demonstrated acceptable goodness-of-fit to the Rasch model. Principal components analyses indicated that both morning and evening assessments demonstrated unidimensionality. Person-separation indices indicated that both morning and evening fatigue scales were able to distinguish four distinct strata of fatigue severity. Excluding four items from the morning fatigue scale and three items from the evening fatigue scale improved the psychometric properties of the LFS for assessing diurnal variations in fatigue severity in oncology patients. Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

Combinatory RNA-Sequencing Analyses Reveal a Dual Mode of Gene Regulation by ADAR1 in Gastric Cancer.

PubMed

Cho, Charles J; Jung, Jaeeun; Jiang, Lushang; Lee, Eun Ji; Kim, Dae-Soo; Kim, Byung Sik; Kim, Hee Sung; Jung, Hwoon-Yong; Song, Ho-June; Hwang, Sung Wook; Park, Yangsoon; Jung, Min Kyo; Pack, Chan Gi; Myung, Seung-Jae; Chang, Suhwan

2018-04-25

Adenosine deaminase acting on RNA 1 (ADAR1) is known to mediate deamination of adenosine-to-inosine through binding to double-stranded RNA, the phenomenon known as RNA editing. Currently, the function of ADAR1 in gastric cancer is unclear. This study was aimed at investigating RNA editing-dependent and editing-independent functions of ADAR1 in gastric cancer, especially focusing on its influence on editing of 3' untranslated regions (UTRs) and subsequent changes in expression of messenger RNAs (mRNAs) as well as microRNAs (miRNAs). RNA-sequencing and small RNA-sequencing were performed on AGS and MKN-45 cells with a stable ADAR1 knockdown. Changed frequencies of editing and mRNA and miRNA expression were then identified by bioinformatic analyses. Targets of RNA editing were further validated in patients' samples. In the Alu region of both gastric cell lines, editing was most commonly of the A-to-I type in 3'-UTR or intron. mRNA and protein levels of PHACTR4 increased in ADAR1 knockdown cells, because of the loss of seed sequences in 3'-UTR of PHACTR4 mRNA that are required for miRNA-196a-3p binding. Immunohistochemical analyses of tumor and paired normal samples from 16 gastric cancer patients showed that ADAR1 expression was higher in tumors than in normal tissues and inversely correlated with PHACTR4 staining. On the other hand, decreased miRNA-148a-3p expression in ADAR1 knockdown cells led to increased mRNA and protein expression of NFYA, demonstrating ADAR1's editing-independent function. ADAR1 regulates post-transcriptional gene expression in gastric cancer through both RNA editing-dependent and editing-independent mechanisms.

Effects of human oral mucosal tissue, saliva and oral microflora on intraoral metabolism and bioactivation of black raspberry anthocyanins

PubMed Central

Mallery, Susan R.; Budendorf, Deric E.; Larsen, Matthew P.; Pei, Ping; Tong, Meng; Holpuch, Andrew S.; Larsen, Peter E.; Stoner, Gary D.; Fields, Henry W.; Chan, Kenneth K.; Ling, Yonghua; Liu, Zhongfa

2011-01-01

Our oral cancer chemoprevention trial data implied that patient-specific differences in local retention and metabolism of freeze-dried black raspberries' (BRB) components affected therapeutic responsiveness. Subsequent studies have confirmed that anthocyanins are key contributors to BRB's chemopreventive effects. Consequently, functional assays, immunoblotting and immunohistochemical analyses to evaluate levels and distribution of BRB anthocyanin-relevant metabolic enzymes in human oral tissues were performed. LC-MS/MS analyses of time course saliva samples collected following BRB rinses were conducted to assess local pharmacokinetics and compare the capacities of three different BRB rinse formulations to provide sustained intraoral levels of anthocyanins. Protein profiles demonstrated the presence of key metabolic enzymes in all 15 oral mucosal tissues evaluated while immunohistochemistry confirmed these enzymes were distributed within surface oral epithelia and terminal salivary ducts. β-glucosidase assays confirmed that whole and microflora-reduced saliva can deglycosylate BRB anthocyanins, enabling generation of the bioactive aglycone, cyanidin. LC-MS/MS analyses demonstrated retention of parent anthocyanins and their functional, stable metabolite, protocatechuic acid, in saliva for up to 4 hours after rinsing. Furthermore, post-rinse saliva samples contained glucuronidated anthocyanin conjugates, consistent with intracellular uptake and Phase II conversion of BRB anthocyanins into forms amenable to local recycling. Our data demonstrate that comparable to the small intestine, the requisite hydrolytic, Phase II and efflux transporting enzymes necessary for local enteric recycling are present and functional in human oral mucosa. Notably, inter-patient differences in anthocyanin bioactivation and capacities for enteric recycling would impact treatment as retention of bioactivated chemopreventives at the target site would sustain therapeutic effectiveness. PMID:21558412

VBM-DTI correlates of verbal intelligence: a potential link to Broca's area.

PubMed

Konrad, Andreas; Vucurevic, Goran; Musso, Francesco; Winterer, Georg

2012-04-01

Human brain lesion studies first investigated the biological roots of cognitive functions including language in the late 1800s. Neuroimaging studies have reported correlation findings with general intelligence predominantly in fronto-parietal cortical areas. However, there is still little evidence about the relationship between verbal intelligence and structural properties of the brain. We predicted that verbal performance is related to language regions of Broca's and Wernicke's areas. Verbal intelligence quotient (vIQ) was assessed in 30 healthy young subjects. T1-weighted MRI and diffusion tensor imaging data sets were acquired. Voxel-wise regression analyses were used to correlate fractional anisotropy (FA) and mean diffusivity values with vIQ. Moreover, regression analyses of regional brain volume with vIQ were performed adopting voxel-based morphometry (VBM) and ROI methodology. Our analyses revealed a significant negative correlation between vIQ and FA and a significant positive correlation between vIQ and mean diffusivity in the left-hemispheric Broca's area. VBM regression analyses did not show significant results, whereas a subsequent ROI analysis of Broca's area FA peak cluster demonstrated a positive correlation of gray matter volume and vIQ. These findings suggest that cortical thickness in Broca's area contributes to verbal intelligence. Diffusion parameters predicted gray matter ratio in Broca's area more sensitive than VBM methodology.

Effects of aging on functional connectivity of the amygdala for subsequent memory of negative pictures: a network analysis of functional magnetic resonance imaging data.

PubMed

St Jacques, Peggy L; Dolcos, Florin; Cabeza, Roberto

2009-01-01

Aging is associated with preserved enhancement of emotional memory, as well as with age-related reductions in memory for negative stimuli, but the neural networks underlying such alterations are not clear. We used a subsequent-memory paradigm to identify brain activity predicting enhanced emotional memory in young and older adults. Activity in the amygdala predicted enhanced emotional memory, with subsequent-memory activity greater for negative stimuli than for neutral stimuli, across age groups, a finding consistent with an overall enhancement of emotional memory. However, older adults recruited greater activity in anterior regions and less activity in posterior regions in general for negative stimuli that were subsequently remembered. Functional connectivity of the amygdala with the rest of the brain was consistent with age-related reductions in memory for negative stimuli: Older adults showed decreased functional connectivity between the amygdala and the hippocampus, but increased functional connectivity between the amygdala and dorsolateral prefrontal cortices. These findings suggest that age-related differences in the enhancement of emotional memory might reflect decreased connectivity between the amygdala and typical subsequent-memory regions, as well as the engagement of regulatory processes that inhibit emotional responses.

Pre- and Postnatal Nutritional Histories Influence Reproductive Maturation and Ovarian Function in the Rat

PubMed Central

Sloboda, Deborah M.; Howie, Graham J.; Pleasants, Anthony; Gluckman, Peter D.; Vickers, Mark H.

2009-01-01

Background While prepubertal nutritional influences appear to play a role in sexual maturation, there is a need to clarify the potential contributions of maternal and childhood influences in setting the tempo of reproductive maturation. In the present study we employed an established model of nutritional programming to evaluate the relative influences of prenatal and postnatal nutrition on growth and ovarian function in female offspring. Methods Pregnant Wistar rats were fed either a calorie-restricted diet, a high fat diet, or a control diet during pregnancy and/or lactation. Offspring then were fed either a control or a high fat diet from the time of weaning to adulthood. Pubertal age was monitored and blood samples collected in adulthood for endocrine analyses. Results We report that in the female rat, pubertal timing and subsequent ovarian function is influenced by the animal's nutritional status in utero, with both maternal caloric restriction and maternal high fat nutrition resulting in early pubertal onset. Depending on the offspring's nutritional history during the prenatal and lactational periods, subsequent nutrition and body weight gain did not further influence offspring reproductive tempo, which was dominated by the effect of prenatal nutrition. Whereas maternal calorie restriction leads to early pubertal onset, it also leads to a reduction in adult progesterone levels later in life. In contrast, we found that maternal high fat feeding which also induces early maturation in offspring was associated with elevated progesterone concentrations. Conclusions These observations are suggestive of two distinct developmental pathways leading to the acceleration of pubertal timing but with different consequences for ovarian function. We suggest different adaptive explanations for these pathways and for their relationship to altered metabolic homeostasis. PMID:19707592

Repeat prostate biopsies prior to radical prostatectomy do not impact erectile function recovery and mid- to long-term continence.

PubMed

Furrer, Marc A; Vilaseca, Antoni; Corradi, Renato B; Boxler, Silvan; Thalmann, George N; Nguyen, Daniel P

2018-06-01

A growing number of men undergo repeat biopsies prior to radical prostatectomy for prostate cancer. However, the long-term impact of repeat biopsies on functional outcomes in this patient population remains unelucidated. Thus, we compared functional outcomes between patients who underwent single biopsy versus repeat biopsies before radical prostatectomy. From 1996 to 2015, 1015 consecutive patients underwent radical prostatectomy, and subsequently had urinary continence and erectile function assessed for >2 years follow-up. One-fourth of patients (275; 27%) had ≥2 biopsies before prostatectomy. Logistic regression models tested whether repeat biopsy before prostatectomy predicted continence or erectile function recovery. For the overall cohort, continence rates were 84%, 92%, 96%, and 98% at 3, 6, 12, and 24 months, respectively. Repeat biopsy before prostatectomy was associated with lower continence rate at 3 months compared to single biopsy (P = 0.03); however, no significant differences were observed at 6, 12, or 24 months. In multivariable analyses adjusting for age, body mass index and diabetes/cardiovascular disease/smoking, the association between repeat biopsy and lower likelihood of continence at 3 months remained (odds ratio 0.67, 95% confidence interval 0.47-0.97; P = 0.03). Overall erectile function recovery rates were 16%, 33%, 51%, and 55% at 3, 6, 12, and 24 months, respectively. No difference in erectile function recovery rates was seen at any time point for single biopsy versus repeat biopsy. In multivariable analyses, repeat biopsy was not predictive of erectile function recovery at any time point. Repeat biopsy before radical prostatectomy impairs early continence after surgery. However, erectile function recovery and mid-term to long-term continence are not affected. These data support the current trend towards active surveillance and delayed local treatment in patients with low- to intermediate-risk prostate cancer. © 2018 Wiley Periodicals, Inc.

Still searching for the engram.

PubMed

Eichenbaum, Howard

2016-09-01

For nearly a century, neurobiologists have searched for the engram-the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories.

Urinary type IV collagen excretion predicts subsequent declining renal function in type 2 diabetic patients with proteinuria.

PubMed

Katavetin, Pisut; Katavetin, Paravee; Susantitaphong, Paweena; Townamchai, Natavudh; Tiranathanagul, Khajohn; Tungsanga, Kriang; Eiam-Ong, Somchai

2010-08-01

Baseline urinary type IV collagen excretion was negatively correlated with the subsequent GFR change (r(s)=-0.39, p=0.04) in our cohort of 30 type 2 diabetic patients with proteinuria. Therefore, it could be used to predict subsequent declining renal function in type 2 diabetic patients with proteinuria. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Task-irrelevant fear enhances amygdala-FFG inhibition and decreases subsequent face processing.

PubMed

Schulte Holthausen, Barbara; Habel, Ute; Kellermann, Thilo; Schelenz, Patrick D; Schneider, Frank; Christopher Edgar, J; Turetsky, Bruce I; Regenbogen, Christina

2016-09-01

Facial threat is associated with changes in limbic activity as well as modifications in the cortical face-related N170. It remains unclear if task-irrelevant threat modulates the response to a subsequent facial stimulus, and whether the amygdala's role in early threat perception is independent and direct, or modulatory. In 19 participants, crowds of emotional faces were followed by target faces and a rating task while simultaneous EEG-fMRI were recorded. In addition to conventional analyses, fMRI-informed EEG analyses and fMRI dynamic causal modeling (DCM) were performed. Fearful crowds reduced EEG N170 target face amplitudes and increased responses in a fMRI network comprising insula, amygdala and inferior frontal cortex. Multimodal analyses showed that amygdala response was present ∼60 ms before the right fusiform gyrus-derived N170. DCM indicated inhibitory connections from amygdala to fusiform gyrus, strengthened when fearful crowds preceded a target face. Results demonstrated the suppressing influence of task-irrelevant fearful crowds on subsequent face processing. The amygdala may be sensitive to task-irrelevant fearful crowds and subsequently strengthen its inhibitory influence on face-responsive fusiform N170 generators. This provides spatiotemporal evidence for a feedback mechanism of the amygdala by narrowing attention in order to focus on potential threats. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

The Tubular Sheaths Encasing Methanosaeta thermophila Filaments Are Functional Amyloids*

PubMed Central

Dueholm, Morten S.; Larsen, Poul; Finster, Kai; Stenvang, Marcel R.; Christiansen, Gunna; Vad, Brian S.; Bøggild, Andreas; Otzen, Daniel E.; Nielsen, Per Halkjær

2015-01-01

Archaea are renowned for their ability to thrive in extreme environments, although they can be found in virtually all habitats. Their adaptive success is linked to their unique cell envelopes that are extremely resistant to chemical and thermal denaturation and that resist proteolysis by common proteases. Here we employ amyloid-specific conformation antibodies and biophysical techniques to show that the extracellular cell wall sheaths encasing the methanogenic archaea Methanosaeta thermophila PT are functional amyloids. Depolymerization of sheaths and subsequent MS/MS analyses revealed that the sheaths are composed of a single major sheath protein (MspA). The amyloidogenic nature of MspA was confirmed by in vitro amyloid formation of recombinant MspA under a wide range of environmental conditions. This is the first report of a functional amyloid from the archaeal domain of life. The amyloid nature explains the extreme resistance of the sheath, the elastic properties that allow diffusible substrates to penetrate through expandable hoop boundaries, and how the sheaths are able to split and elongate outside the cell. The archaeal sheath amyloids do not share homology with any of the currently known functional amyloids and clearly represent a new function of the amyloid protein fold. PMID:26109065

Phylogenetic and Functional Structure of Wintering Waterbird Communities Associated with Ecological Differences.

PubMed

Che, Xianli; Zhang, Min; Zhao, Yanyan; Zhang, Qiang; Quan, Qing; Møller, Anders; Zou, Fasheng

2018-01-19

Ecological differences may be related to community component divisions between Oriental (west) and Sino-Japanese (east) realms, and such differences may result in weak geographical breaks in migratory species that are highly mobile. Here, we conducted comparative phylogenetic and functional structure analyses of wintering waterbird communities in southern China across two realms and subsequently examined possible climate drivers of the observed patterns. An analysis based on such highly migratory species is particularly telling because migration is bound to reduce or completely eliminate any divergence between communities. Phylogenetic and functional structure of eastern communities showed over-dispersion while western communities were clustered. Basal phylogenetic and functional turnover of western communities was significant lower than that of eastern communities. The break between eastern and western communities was masked by these two realms. Geographic patterns were related to mean temperature changes and temperature fluctuations, suggesting that temperature may filter waterbird lineages and traits, thus underlying geographical community divisions. These results suggest phylogenetic and functional divisions in southern China, coinciding with biogeography. This study shows that temperature fluctuations constitute an essential mechanism shaping geographical divisions that have largely gone undetected previously, even under climate change.

Profiling the outer membrane proteome during growth and development of the social bacterium Myxococcus xanthus by selective biotinylation and analyses of outer membrane vesicles.

PubMed

Kahnt, Jörg; Aguiluz, Kryssia; Koch, Jürgen; Treuner-Lange, Anke; Konovalova, Anna; Huntley, Stuart; Hoppert, Michael; Søgaard-Andersen, Lotte; Hedderich, Reiner

2010-10-01

Social behavior in the bacterium Myxococcus xanthus relies on contact-dependent activities involving cell-cell and cell-substratum interactions. To identify outer membrane proteins that have a role in these activities, we profiled the outer membrane proteome of growing and starving cells using two strategies. First, outer membrane proteins were enriched by biotinylation of intact cells using the reagent NHS (N-hydroxysuccinimide)-PEO(12) (polyethylene oxide)-biotin with subsequent membrane solubilization and affinity chromatography. Second, the proteome of outer membrane vesicles (OMV) was determined. Comparisons of detected proteins show that these methods have different detection profiles and together provide a comprehensive view of the outer membrane proteome. From 362 proteins identified, 274 (76%) were cell envelope proteins including 64 integral outer membrane proteins and 85 lipoproteins. The majority of these proteins were of unknown function. Among integral outer membrane proteins with homologues of known function, TonB-dependent transporters comprise the largest group. Our data suggest novel functions for these transporters. Among lipoproteins with homologues of known function, proteins with hydrolytic functions comprise the largest group. The luminal load of OMV was enriched for proteins with hydrolytic functions. Our data suggest that OMV have functions in predation and possibly in transfer of intercellular signaling molecules between cells.

Petascale supercomputing to accelerate the design of high-temperature alloys

DOE PAGES

Shin, Dongwon; Lee, Sangkeun; Shyam, Amit; ...

2017-10-25

Recent progress in high-performance computing and data informatics has opened up numerous opportunities to aid the design of advanced materials. Herein, we demonstrate a computational workflow that includes rapid population of high-fidelity materials datasets via petascale computing and subsequent analyses with modern data science techniques. We use a first-principles approach based on density functional theory to derive the segregation energies of 34 microalloying elements at the coherent and semi-coherent interfaces between the aluminium matrix and the θ'-Al 2Cu precipitate, which requires several hundred supercell calculations. We also perform extensive correlation analyses to identify materials descriptors that affect the segregation behaviourmore » of solutes at the interfaces. Finally, we show an example of leveraging machine learning techniques to predict segregation energies without performing computationally expensive physics-based simulations. As a result, the approach demonstrated in the present work can be applied to any high-temperature alloy system for which key materials data can be obtained using high-performance computing.« less

Petascale supercomputing to accelerate the design of high-temperature alloys

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

Shin, Dongwon; Lee, Sangkeun; Shyam, Amit

Recent progress in high-performance computing and data informatics has opened up numerous opportunities to aid the design of advanced materials. Herein, we demonstrate a computational workflow that includes rapid population of high-fidelity materials datasets via petascale computing and subsequent analyses with modern data science techniques. We use a first-principles approach based on density functional theory to derive the segregation energies of 34 microalloying elements at the coherent and semi-coherent interfaces between the aluminium matrix and the θ'-Al 2Cu precipitate, which requires several hundred supercell calculations. We also perform extensive correlation analyses to identify materials descriptors that affect the segregation behaviourmore » of solutes at the interfaces. Finally, we show an example of leveraging machine learning techniques to predict segregation energies without performing computationally expensive physics-based simulations. As a result, the approach demonstrated in the present work can be applied to any high-temperature alloy system for which key materials data can be obtained using high-performance computing.« less

Petascale supercomputing to accelerate the design of high-temperature alloys

NASA Astrophysics Data System (ADS)

Shin, Dongwon; Lee, Sangkeun; Shyam, Amit; Haynes, J. Allen

2017-12-01

Recent progress in high-performance computing and data informatics has opened up numerous opportunities to aid the design of advanced materials. Herein, we demonstrate a computational workflow that includes rapid population of high-fidelity materials datasets via petascale computing and subsequent analyses with modern data science techniques. We use a first-principles approach based on density functional theory to derive the segregation energies of 34 microalloying elements at the coherent and semi-coherent interfaces between the aluminium matrix and the θ‧-Al2Cu precipitate, which requires several hundred supercell calculations. We also perform extensive correlation analyses to identify materials descriptors that affect the segregation behaviour of solutes at the interfaces. Finally, we show an example of leveraging machine learning techniques to predict segregation energies without performing computationally expensive physics-based simulations. The approach demonstrated in the present work can be applied to any high-temperature alloy system for which key materials data can be obtained using high-performance computing.

Assessing the impact of fishing in shallow rocky reefs: a multivariate approach to ecosystem management.

PubMed

Sangil, Carlos; Martín-García, Laura; Clemente, Sabrina

2013-11-15

In this paper we develop a tool to assess the impact of fishing on ecosystem functioning in shallow rocky reefs. The relationships between biological parameters (fishes, sea urchins, seaweeds), and fishing activities (fish traps, boats, land-based fishing, spearfishing) were tested in La Palma island (Canary Islands). Data from fishing activities and biological parameters were analyzed using principal component analyses. We produced two models using the first component of these analyses. This component was interpreted as a new variable that described the fishing pressure and the conservation status at each studied site. Subsequently the scores on the first axis were mapped using universal kriging methods and the models obtained were extrapolated across the whole island to display the expected fishing pressure and conservation status more widely. The fishing pressure and conservation status models were spatially related; zones where fishing pressure was high coincided with zones in the unhealthiest ecological state. Copyright © 2013 Elsevier Ltd. All rights reserved.

Similarity Measures for Protein Ensembles

PubMed Central

Lindorff-Larsen, Kresten; Ferkinghoff-Borg, Jesper

2009-01-01

Analyses of similarities and changes in protein conformation can provide important information regarding protein function and evolution. Many scores, including the commonly used root mean square deviation, have therefore been developed to quantify the similarities of different protein conformations. However, instead of examining individual conformations it is in many cases more relevant to analyse ensembles of conformations that have been obtained either through experiments or from methods such as molecular dynamics simulations. We here present three approaches that can be used to compare conformational ensembles in the same way as the root mean square deviation is used to compare individual pairs of structures. The methods are based on the estimation of the probability distributions underlying the ensembles and subsequent comparison of these distributions. We first validate the methods using a synthetic example from molecular dynamics simulations. We then apply the algorithms to revisit the problem of ensemble averaging during structure determination of proteins, and find that an ensemble refinement method is able to recover the correct distribution of conformations better than standard single-molecule refinement. PMID:19145244

Modulation of interaction of mutant TP53 and wild type BRCA1 by alkaloids: a computational approach towards targeting protein-protein interaction as a futuristic therapeutic intervention strategy for breast cancer impediment.

PubMed

Tiwari, Sameeksha; Awasthi, Manika; Singh, Swati; Pandey, Veda P; Dwivedi, Upendra N

2017-10-23

Protein-protein interactions (PPI) are a new emerging class of novel therapeutic targets. In order to probe these interactions, computational tools provide a convenient and quick method towards the development of therapeutics. Keeping this in view the present study was initiated to analyse interaction of tumour suppressor protein p53 (TP53) and breast cancer associated protein (BRCA1) as promising target against breast cancer. Using computational approaches such as protein-protein docking, hot spot analyses, molecular docking and molecular dynamics simulation (MDS), stepwise analyses of the interactions of the wild type and mutant TP53 with that of wild type BRCA1 and their modulation by alkaloids were done. Protein-protein docking method was used to generate both wild type and mutant complexes of TP53-BRCA1. Subsequently, the complexes were docked using sixteen different alkaloids, fulfilling ADMET and Lipinski's rule of five criteria, and were compared with that of a well-known inhibitor of PPI, namely nutlin. The alkaloid dicentrine was found to be the best docked alkaloid among all the docked alklaloids as well as that of nutlin. Furthermore, MDS analyses of both wild type and mutant complexes with the best docked alkaloid i.e. dicentrine, revealed higher stability of mutant complex than that of the wild one, in terms of average RMSD, RMSF and binding free energy, corroborating the results of docking. Results suggested more pronounced interaction of BRCA1 with mutant TP53 leading to increased expression of mutated TP53 thus showing a dominant negative gain of function and hampering wild type TP53 function leading to tumour progression.

Fused Traditional and Geometric Morphometrics Demonstrate Pinniped Whisker Diversity

PubMed Central

Ginter, Carly C.; DeWitt, Thomas J.; Fish, Frank E.; Marshall, Christopher D.

2012-01-01

Vibrissae (whiskers) are important components of the mammalian tactile sensory system, and primarily function as detectors of vibrotactile information from the environment. Pinnipeds possess the largest vibrissae among mammals and their vibrissal hair shafts demonstrate a diversity of shapes. The vibrissae of most phocid seals exhibit a beaded morphology with repeating sequences of crests and troughs along their length. However, there are few detailed analyses of pinniped vibrissal morphology, and these are limited to a few species. Therefore, we comparatively characterized differences in vibrissal hair shaft morphologies among phocid species with a beaded profile, phocid species with a smooth profile, and otariids with a smooth profile using traditional and geometric morphometric methods. Traditional morphometric measurements (peak-to-peak distance, crest width, trough width and total length) were collected using digital photographs. Elliptic Fourier analysis (geometric morphometrics) was used to quantify the outlines of whole vibrissae. The traditional and geometric morphometric datasets were subsequently combined by mathematically scaling each to true rank, followed by a single eigendecomposition. Quadratic discriminant function analysis demonstrated that 79.3, 97.8 and 100% of individuals could be correctly classified to their species based on vibrissal shape variables in the traditional, geometric and combined morphometric analyses, respectively. Phocids with beaded vibrissae, phocids with smooth vibrissae, and otariids each occupied distinct morphospace in the geometric morphometric and combined data analyses. Otariids split into two groups in the geometric morphometric analysis and gray seals appeared intermediate between beaded- and smooth-whiskered species in the traditional and combined analyses. Vibrissal hair shafts modulate the transduction of environmental stimuli to the mechanoreceptors in the follicle-sinus complex (F-SC), which results in vibrotactile reception, but it is currently unclear how the diversity of shapes affects environmental signal modulation. PMID:22509310

Characterization of the Bacillus stearothermophilus manganese superoxide dismutase gene and its ability to complement copper/zinc superoxide dismutase deficiency in Saccharomyces cerevisiae

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

Bowler, C.; Inze, D.; Van Camp, W.

1990-03-01

Recombinant clones containing the manganese superoxide dismutase (MnSOD) gene of Bacillus stearothermophilus were isolated with an oligonucleotide probe designed to match a part of the previously determined amino acid sequence. Complementation analyses, performed by introducing each plasmid into a superoxide dismutase-deficient mutant of Escherichia coli, allowed us to define the region of DNA which encodes the MnSOD structural gene and to identify a promoter region immediately upstream from the gene. These data were subsequently confirmed by DNA sequencing. Since MnSOD is normally restricted to the mitochondria in eucaryotes, we were interested (i) in determining whether B. stearothermophilus MnSOD could functionmore » in eucaryotic cytosol and (ii) in determining whether MnSOD could replace the structurally unrelated copper/zinc superoxide dismutase (Cu/ZnSOD) which is normally found there. To test this, the sequence encoding bacterial MnSOD was cloned into a yeast expression vector and subsequently introduced into a Cu/ZnSOD-deficient mutant of the yeast Saccharomyces cerevisiae. Functional expression of the protein was demonstrated, and complementation tests revealed that the protein was able to provide tolerance at wild-type levels to conditions which are normally restrictive for this mutant. Thus, in spite of the evolutionary unrelatedness of these two enzymes, Cu/ZnSOD can be functionally replaced by MnSOD in yeast cytosol.« less

Communication changes experienced by adults with cerebral palsy as they age.

PubMed

Dark, Leigha Jane; Clemson, Lindy; Balandin, Susan

2016-12-01

Adults with cerebral palsy (CP) experience multiple, functional changes as they age, including changes to communication modes and methods that enable development and maintenance of relationships, communicative participation and quality-of-life. Little is known about the nature of communication changes experienced by this group. The aim of this study was to better understand how adults with CP experience changes in their communication abilities as they age and the subsequent psychosocial impact. Twenty adults with cerebral palsy aged 40-72 years with complex communication needs (CCN) participated in a series of in-depth interviews, framing their experiences of loss and grief throughout their lives. The impact of changing communication abilities emerged as an important area of focus. Data were analysed using constructivist grounded theory methodology. Themes arising from the participants' perceptions of their communication included experiencing communication change as a loss with subsequent impact on self-concept; and how communication is integral to the process of managing losses associated with older age. Implications for speech-language pathologists working with older people with cerebral palsy and CCN include the need to understand the psychosocial impact of communication changes on social interaction, relationships and communicative participation. It is important to promote positive and meaningful communication options that maintain a coherent sense of self in addition to promoting functional communication skills and communicative participation.

Resting-state Functional Connectivity is an Age-dependent Predictor of Motor Learning Abilities.

PubMed

Mary, Alison; Wens, Vincent; Op de Beeck, Marc; Leproult, Rachel; De Tiège, Xavier; Peigneux, Philippe

2017-10-01

This magnetoencephalography study investigates how ageing modulates the relationship between pre-learning resting-state functional connectivity (rsFC) and subsequent learning. Neuromagnetic resting-state activity was recorded 5 min before motor sequence learning in 14 young (19-30 years) and 14 old (66-70 years) participants. We used a seed-based beta-band power envelope correlation approach to estimate rsFC maps, with the seed located in the right primary sensorimotor cortex. In each age group, the relation between individual rsFC and learning performance was investigated using Pearson's correlation analyses. Our results show that rsFC is predictive of subsequent motor sequence learning but involves different cross-network interactions in the two age groups. In young adults, decreased coupling between the sensorimotor network and the cortico-striato-cerebellar network is associated with better motor learning, whereas a similar relation is found in old adults between the sensorimotor, the dorsal-attentional and the DMNs. Additionally, age-related correlational differences were found in the dorsolateral prefrontal cortex, known to subtend attentional and controlled processes. These findings suggest that motor skill learning depends-in an age-dependent manner-on subtle interactions between resting-state networks subtending motor activity on the one hand, and controlled and attentional processes on the other hand. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Genetic and structural analyses of cytochrome P450 hydroxylases in sex hormone biosynthesis: Sequential origin and subsequent coevolution.

PubMed

Goldstone, Jared V; Sundaramoorthy, Munirathinam; Zhao, Bin; Waterman, Michael R; Stegeman, John J; Lamb, David C

2016-01-01

Biosynthesis of steroid hormones in vertebrates involves three cytochrome P450 hydroxylases, CYP11A1, CYP17A1 and CYP19A1, which catalyze sequential steps in steroidogenesis. These enzymes are conserved in the vertebrates, but their origin and existence in other chordate subphyla (Tunicata and Cephalochordata) have not been clearly established. In this study, selected protein sequences of CYP11A1, CYP17A1 and CYP19A1 were compiled and analyzed using multiple sequence alignment and phylogenetic analysis. Our analyses show that cephalochordates have sequences orthologous to vertebrate CYP11A1, CYP17A1 or CYP19A1, and that echinoderms and hemichordates possess CYP11-like but not CYP19 genes. While the cephalochordate sequences have low identity with the vertebrate sequences, reflecting evolutionary distance, the data show apparent origin of CYP11 prior to the evolution of CYP19 and possibly CYP17, thus indicating a sequential origin of these functionally related steroidogenic CYPs. Co-occurrence of the three CYPs in early chordates suggests that the three genes may have coevolved thereafter, and that functional conservation should be reflected in functionally important residues in the proteins. CYP19A1 has the largest number of conserved residues while CYP11A1 sequences are less conserved. Structural analyses of human CYP11A1, CYP17A1 and CYP19A1 show that critical substrate binding site residues are highly conserved in each enzyme family. The results emphasize that the steroidogenic pathways producing glucocorticoids and reproductive steroids are several hundred million years old and that the catalytic structural elements of the enzymes have been conserved over the same period of time. Analysis of these elements may help to identify when precursor functions linked to these enzymes first arose. Copyright © 2015 Elsevier Inc. All rights reserved.

Bifunctional application of sodium cobaltate as a catalyst and captor through CO oxidation and subsequent CO 2 chemisorption processes

DOE PAGES

Vera, Elizabeth; Alcántar-Vázquez, Brenda; Duan, Yuhua; ...

2015-12-21

The potential bifunctional mechanism of sodium cobaltate (NaCoO 2) in the catalysis of CO oxidation and subsequent CO 2 chemisorption was systematically analysed. Different catalytic and gravimetric experiments were performed dynamically and isothermally at multiple temperatures. Initially, the CO oxidation process was evaluated using a catalytic reactor connected to a gas chromatograph. Once the production of CO 2 was confirmed, its chemisorption capacity with NaCoO 2 was studied gravimetrically. Catalytic and gravimetric analysis products were studied by XRD, FTIR and SEM to elucidate the double reaction mechanism. Sodium cobaltate exhibited interesting catalytic properties over a wide temperature range, although themore » NaCoO 2 crystalline structure and chemical composition changed during the CO 2 capture process. Furthermore, all the experiments were theoretically supported by first-principles density functional theory thermodynamic calculations. Finally, the calculated thermodynamic properties of the CO oxidation and CO 2 capture reactions with NaCoO 2 under different oxidation conditions were in good agreement with the experimental measurements.« less

The double-stranded transcriptome of Escherichia coli.

PubMed

Lybecker, Meghan; Zimmermann, Bob; Bilusic, Ivana; Tukhtubaeva, Nadezda; Schroeder, Renée

2014-02-25

Advances in high-throughput transcriptome analyses have revealed hundreds of antisense RNAs (asRNAs) for many bacteria, although few have been characterized, and the number of functional asRNAs remains unknown. We have developed a genome-wide high-throughput method to identify functional asRNAs in vivo. Most mechanisms of gene regulation via asRNAs require an RNA-RNA interaction with its target RNA, and we hypothesized that a functional asRNA would be found in a double strand (dsRNA), duplexed with its cognate RNA in a single cell. We developed a method of isolating dsRNAs from total RNA by immunoprecipitation with a ds-RNA specific antibody. Total RNA and immunoprecipitated dsRNA from Escherichia coli RNase III WT and mutant strains were deep-sequenced. A statistical model was applied to filter for biologically relevant dsRNA regions, which were subsequently categorized by location relative to annotated genes. A total of 316 potentially functional asRNAs were identified in the RNase III mutant strain and are encoded primarily opposite to the 5' ends of transcripts, but are also found opposite ncRNAs, gene junctions, and the 3' ends. A total of 21 sense/antisense RNA pairs identified in dsRNAs were confirmed by Northern blot analyses. Most of the RNA steady-state levels were higher or detectable only in the RNase III mutant strain. Taken together, our data indicate that a significant amount of dsRNA is formed in the cell, that RNase III degrades or processes these dsRNAs, and that dsRNA plays a major role in gene regulation in E. coli.

The impact of conscientiousness, mastery, and work circumstances on subsequent absenteeism in employees with and without affective disorders.

PubMed

Kok, Almar A L; Plaisier, Inger; Smit, Johannes H; Penninx, Brenda W J H

2017-03-29

High numbers of employees are coping with affective disorders. At the same time, ambitiousness, achievement striving and a strong sense of personal control and responsibility are personality characteristics that are nowadays regarded as key to good work functioning, whereas social work circumstances tend to be neglected. However, it is largely unkown how personality characteristics and work circumstances affect work functioning when facing an affective disorder. Given the high burden of affective disorders on occupational health, we investigate these issues in the context of affective disorders and absenteeism from work. The principal aim of this paper is to examine whether particular personality characteristics that reflect self-governance (conscientiousness and mastery) and work circumstances (demands, control, support) influence the impact of affective disorders on long-term absenteeism (>10 working days). Baseline and 1-year follow-up data from 1249 participants in the Netherlands Study of Depression and Anxiety (NESDA) in 2004-2006 was employed. Multivariate logistic regression analyses were performed, including interaction effects between depressive, anxiety, and comorbid disorders and personality and work circumstances. In general, mastery and conscientiousness increased nor diminished odds of subsequent long-term absenteeism, whereas higher job support significantly decreased these odds. Interaction effects showed that the impact of affective disorders on absenteeism was stronger for highly conscientious employees and for employees who experienced high job demands. Affective disorders may particularly severely affect work functioning of employees who are highly conscientious or face high psychological job demands. Adjusting working conditions to their individual needs may prevent excessive work absence.

PPAR-γ Ameliorates Neuronal Apoptosis and Ischemic Brain Injury via Suppressing NF-κB-Driven p22phox Transcription.

PubMed

Wu, Jui-Sheng; Tsai, Hsin-Da; Cheung, Wai-Mui; Hsu, Chung Y; Lin, Teng-Nan

2016-08-01

Peroxisome proliferator-activated receptor-gamma (PPAR-γ), a stress-induced transcription factor, protects neurons against ischemic stroke insult by reducing oxidative stress. NADPH oxidase (NOX) activation, a major driving force in ROS generation in the setting of reoxygenation/reperfusion, constitutes an important pathogenetic mechanism of ischemic brain damage. In the present study, both transient in vitro oxygen-glucose deprivation and in vivo middle cerebral artery (MCA) occlusion-reperfusion experimental paradigms of ischemic neuronal death were used to investigate the interaction between PPAR-γ and NOX. With pharmacological (PPAR-γ antagonist GW9662), loss-of-function (PPAR-γ siRNA), and gain-of-function (Ad-PPAR-γ) approaches, we first demonstrated that 15-deoxy-∆(12,14)-PGJ2 (15d-PGJ2), via selectively attenuating p22phox expression, inhibited NOX activation and the subsequent ROS generation and neuronal death in a PPAR-γ-dependent manner. Secondly, results of promoter analyses and subcellular localization studies further revealed that PPAR-γ, via inhibiting hypoxia-induced NF-κB nuclear translocation, indirectly suppressed NF-κB-driven p22phox transcription. Noteworthily, postischemic p22phox siRNA treatment not only reduced infarct volumes but also improved functional outcome. In summary, we report a novel transrepression mechanism involving PPAR-γ downregulation of p22phox expression to suppress the subsequent NOX activation, ischemic neuronal death, and brain infarct. Identification of a PPAR-γ → NF-κB → p22phox neuroprotective signaling cascade opens a new avenue for protecting the brain against ischemic insult.

Reactions to abortion and subsequent mental health.

PubMed

Fergusson, David M; Horwood, L John; Boden, Joseph M

2009-11-01

There has been continued interest in the extent to which women have positive and negative reactions to abortion. To document emotional reactions to abortion, and to examine the links between reactions to abortion and subsequent mental health outcomes. Data were gathered on the pregnancy and mental health history of a birth cohort of over 500 women studied to the age of 30. Abortion was associated with high rates of both positive and negative emotional reactions; however, nearly 90% of respondents believed that the abortion was the right decision. Analyses showed that the number of negative responses to the abortion was associated with increased levels of subsequent mental health disorders (P<0.05). Further analyses suggested that, after adjustment for confounding, those having an abortion and reporting negative reactions had rates of mental health disorders that were approximately 1.4-1.8 times higher than those not having an abortion. Abortion was associated with both positive and negative emotional reactions. The extent of negative emotional reactions appeared to modify the links between abortion and subsequent mental health problems.

Mosaic Convergence of Rodent Dentitions

PubMed Central

Lazzari, Vincent; Charles, Cyril; Tafforeau, Paul; Vianey-Liaud, Monique; Aguilar, Jean-Pierre; Jaeger, Jean-Jacques; Michaux, Jacques; Viriot, Laurent

2008-01-01

Background Understanding mechanisms responsible for changes in tooth morphology in the course of evolution is an area of investigation common to both paleontology and developmental biology. Detailed analyses of molar tooth crown shape have shown frequent homoplasia in mammalian evolution, which requires accurate investigation of the evolutionary pathways provided by the fossil record. The necessity of preservation of an effective occlusion has been hypothesized to functionally constrain crown morphological changes and to also facilitate convergent evolution. The Muroidea superfamily constitutes a relevant model for the study of molar crown diversification because it encompasses one third of the extant mammalian biodiversity. Methodology/Principal Findings Combined microwear and 3D-topographic analyses performed on fossil and extant muroid molars allow for a first quantification of the relationships between changes in crown morphology and functionality of occlusion. Based on an abundant fossil record and on a well resolved phylogeny, our results show that the most derived functional condition associates longitudinal chewing and non interlocking of cusps. This condition has been reached at least 7 times within muroids via two main types of evolutionary pathways each respecting functional continuity. In the first type, the flattening of tooth crown which induces the removal of cusp interlocking occurs before the rotation of the chewing movement. In the second type however, flattening is subsequent to rotation of the chewing movement which can be associated with certain changes in cusp morphology. Conclusion/Significance The reverse orders of the changes involved in these different pathways reveal a mosaic evolution of mammalian dentition in which direction of chewing and crown shape seem to be partly decoupled. Either can change in respect to strong functional constraints affecting occlusion which thereby limit the number of the possible pathways. Because convergent pathways imply distinct ontogenetic trajectories, new Evo/Devo comparative studies on cusp morphogenesis are necessary. PMID:18974837

The associations between weight-related anthropometrics during childhood and lung function in late childhood: a retrospective cohort study.

PubMed

Byberg, Kristine Kjer; Mikalsen, Ingvild Bruun; Eide, Geir Egil; Forman, Michele R; Júlíusson, Pétur Benedikt; Øymar, Knut

2018-01-19

An association between body weight in childhood and subsequent lung function and asthma has been suggested, but few longitudinal studies exist. Our aim was to explore whether weight-related anthropometric measurements through childhood were associated with lung function in late childhood. From an original nested case-control study, a cohort study was conducted, where lung function was measured in 463 children aged 12.8 years, and anthropometry was measured at several ages from birth through 12.8 years of age. Associations between anthropometrics and lung function were analysed using multiple linear and fractional polynomial regression analysis. Birthweight and body mass index (BMI; kg/m 2 ) at different ages through childhood were positively associated with forced vital capacity in percent of predicted (FVC %) and forced expiratory volume in the first second in percent of predicted (FEV 1 %) at 12.8 years of age. BMI, waist circumference, waist-to-height ratio and skinfolds at 12.8 years of age and the change in BMI from early to late childhood were positively associated with FVC % and FEV 1 % and negatively associated with FEV 1 /FVC and forced expiratory flow at 25-75% of FVC/FVC. Interaction analyses showed that positive associations between anthropometrics other than BMI and lung function were mainly found in girls. Inverse U-shaped associations were found between BMI at the ages of 10.8/11.8 (girls/boys) and 12.8 years (both genders) and FVC % and FEV 1 % at 12.8 years of age. Weight-related anthropometrics through childhood may influence lung function in late childhood. These findings may be physiological or associated with air flow limitation. Inverse U-shaped associations suggest a differential impact on lung function in normal-weight and overweight children. This study was observational without any health care intervention for the participants. Therefore, no trial registration number is available.

Characterizing the “POAGome”: A bioinformatics-driven approach to primary open-angle glaucoma

PubMed Central

Danford, Ian D.; Verkuil, Lana D.; Choi, Daniel J.; Collins, David W.; Gudiseva, Harini V.; Uyhazi, Katherine E.; Lau, Marisa K.; Kanu, Levi N.; Grant, Gregory R.; Chavali, Venkata R.M.; O’Brien, Joan M.

2017-01-01

Primary open-angle glaucoma (POAG) is a genetically, physiologically, and phenotypically complex neurodegenerative disorder. This study addressed the expanding collection of genes associated with POAG, referred to as the “POAGome.” We used bioinformatics tools to perform an extensive, systematic literature search and compiled 542 genes with confirmed associations with POAG and its related phenotypes (normal tension glaucoma, ocular hypertension, juvenile open-angle glaucoma, and primary congenital glaucoma). The genes were classified according to their associated ocular tissues and phenotypes, and functional annotation and pathway analyses were subsequently performed. Our study reveals that no single molecular pathway can encompass the pathophysiology of POAG. The analyses suggested that inflammation and senescence may play pivotal roles in both the development and perpetuation of the retinal ganglion cell degeneration seen in POAG. The TGF-β signaling pathway was repeatedly implicated in our analyses, suggesting that it may be an important contributor to the manifestation of POAG in the anterior and posterior segments of the globe. We propose a molecular model of POAG revolving around TGF-β signaling, which incorporates the roles of inflammation and senescence in this disease. Finally, we highlight emerging molecular therapies that show promise for treating POAG. PMID:28223208

Identifying Useful Auxiliary Variables for Incomplete Data Analyses: A Note on a Group Difference Examination Approach

ERIC Educational Resources Information Center

Raykov, Tenko; Marcoulides, George A.

2014-01-01

This research note contributes to the discussion of methods that can be used to identify useful auxiliary variables for analyses of incomplete data sets. A latent variable approach is discussed, which is helpful in finding auxiliary variables with the property that if included in subsequent maximum likelihood analyses they may enhance considerably…

Metatranscriptome analysis of the microbial fermentation of dietary milk proteins in the murine gut.

PubMed

Hugenholtz, Floor; Davids, Mark; Schwarz, Jessica; Müller, Michael; Tomé, Daniel; Schaap, Peter; Hooiveld, Guido J E J; Smidt, Hauke; Kleerebezem, Michiel

2018-01-01

Undigestible food ingredients are converted by the microbiota into a large range of metabolites, predominated by short chain fatty acids (SCFA). These microbial metabolites are subsequently available for absorption by the host mucosa and can serve as an energy source. Amino acids fermentation by the microbiota expands the spectrum of fermentation end-products beyond acetate, propionate and butyrate, to include in particular branched-SCFA. Here the long-term effects of high protein-diets on microbial community composition and functionality in mice were analyzed. Determinations of the microbiota composition using phylogenetic microarray (MITChip) technology were complemented with metatranscriptome and SCFA analyses to obtain insight in in situ expression of protein fermentation pathways and the phylogenetic groups involved. High protein diets led to increased luminal concentrations of branched-SCFA, in accordance with protein fermentation in the gut. Bacteria dominantly participating in protein catabolism belonged to the Lachnospiraceae, Erysipelotrichaceae and Clostridiaceae families in both normal- and high- protein diet regimes. This study identifies the microbial groups involved in protein catabolism in the intestine and underpins the value of in situ metatranscriptome analyses as an approach to decipher locally active metabolic networks and pathways as a function of the dietary regime, as well as the phylogeny of the microorganisms executing them.

Predation risk modifies behaviour by shaping the response of identified brain neurons.

PubMed

Magani, Fiorella; Luppi, Tomas; Nuñez, Jesus; Tomsic, Daniel

2016-04-15

Interpopulation comparisons in species that show behavioural variations associated with particular ecological disparities offer good opportunities for assessing how environmental factors may foster specific functional adaptations in the brain. Yet, studies on the neural substrate that can account for interpopulation behavioural adaptations are scarce. Predation is one of the strongest driving forces for behavioural evolvability and, consequently, for shaping structural and functional brain adaptations. We analysed the escape response of crabs ITALIC! Neohelice granulatafrom two isolated populations exposed to different risks of avian predation. Individuals from the high-risk area proved to be more reactive to visual danger stimuli (VDS) than those from an area where predators are rare. Control experiments indicate that the response difference was specific for impending visual threats. Subsequently, we analysed the response to VDS of a group of giant brain neurons that are thought to play a main role in the visually guided escape response of the crab. Neurons from animals of the population with the stronger escape response were more responsive to VDS than neurons from animals of the less reactive population. Our results suggest a robust linkage between the pressure imposed by the predation risk, the response of identified neurons and the behavioural outcome. © 2016. Published by The Company of Biologists Ltd.

Electromyographic activity associated with spontaneous functional recovery after spinal cord injury in rats.

PubMed

Kaegi, Sibille; Schwab, Martin E; Dietz, Volker; Fouad, Karim

2002-07-01

This investigation was designed to study the spontaneous functional recovery of adult rats with incomplete spinal cord injury (SCI) at thoracic level during a time course of 2 weeks. Daily testing sessions included open field locomotor examination and electromyographic (EMG) recordings from a knee extensor (vastus lateralis, VL) and an ankle flexor muscle (tibialis anterior, TA) in the hindlimbs of treadmill walking rats. The BBB score (a locomotor score named after Basso et al., 1995, J. Neurotrauma, 12, 1-21) and various measures from EMG recordings were analysed (i.e. step cycle duration, rhythmicity of limb movements, flexor and extensor burst duration, EMG amplitude, root-mean-square, activity overlap between flexor and extensor muscles and hindlimb coupling). Directly after SCI, a marked drop in locomotor ability occurred in all rats with subsequent partial recovery over 14 days. The recovery was most pronounced during the first week. Significant changes were noted in the recovery of almost all analysed EMG measures. Within the 14 days of recovery, many of these measures approached control levels. Persistent abnormalities included a prolonged flexor burst and increased activity overlap between flexor and extensor muscles. Activity overlap between flexor and extensor muscles might be directly caused by altered descending input or by maladaptation of central pattern generating networks and/or sensory feedback.

Modelling Comparative Efficacy of Drugs with Different Survival Profiles: Ipilimumab, Vemurafenib and Dacarbazine in Advanced Melanoma.

PubMed

Lee, D; Porter, J; Hertel, N; Hatswell, A J; Briggs, A

2016-08-01

In the absence of head-to-head data, a common method for modelling comparative survival for cost-effectiveness analysis is estimating hazard ratios from trial publications. This assumes that the hazards of mortality are proportional between treatments and that outcomes are not polluted by subsequent therapy use. Newer techniques that compare treatments where the proportional hazards assumption is violated and adjust for use of subsequent therapies often require patient-level data, which are rarely available for all treatments. The objective of this study was to provide a comparison of overall survival data for ipilimumab, vemurafenib and dacarbazine using data from three trials lacking a common comparator arm and confounded by the use of subsequent treatment. We compared three estimated overall survival curves for vemurafenib and the difference compared to ipilimumab and dacarbazine. We performed a naïve comparison and adjusted it for heterogeneity between the ipilimumab and vemurafenib trials, including differences in prognostic characteristics and subsequent therapy using a published hazard function for the impact of prognostic characteristics in melanoma and trial data on the impact of second-line use of ipilimumab. The mean incremental life-years gained for patients receiving ipilimumab compared with vemurafenib were 0.34 (95 % confidence interval [CI] -0.24 to 0.84) using the naïve comparison and 0.51 (95 % CI -0.08 to 0.99) using the covariate-adjusted survival curve. The analyses estimated the comparative efficacy of ipilimumab and vemurafenib in the absence of head-to-head patient-level data for all trials and proportional hazards in overall survival.

The smart cluster method. Adaptive earthquake cluster identification and analysis in strong seismic regions

NASA Astrophysics Data System (ADS)

Schaefer, Andreas M.; Daniell, James E.; Wenzel, Friedemann

2017-07-01

Earthquake clustering is an essential part of almost any statistical analysis of spatial and temporal properties of seismic activity. The nature of earthquake clusters and subsequent declustering of earthquake catalogues plays a crucial role in determining the magnitude-dependent earthquake return period and its respective spatial variation for probabilistic seismic hazard assessment. This study introduces the Smart Cluster Method (SCM), a new methodology to identify earthquake clusters, which uses an adaptive point process for spatio-temporal cluster identification. It utilises the magnitude-dependent spatio-temporal earthquake density to adjust the search properties, subsequently analyses the identified clusters to determine directional variation and adjusts its search space with respect to directional properties. In the case of rapid subsequent ruptures like the 1992 Landers sequence or the 2010-2011 Darfield-Christchurch sequence, a reclassification procedure is applied to disassemble subsequent ruptures using near-field searches, nearest neighbour classification and temporal splitting. The method is capable of identifying and classifying earthquake clusters in space and time. It has been tested and validated using earthquake data from California and New Zealand. A total of more than 1500 clusters have been found in both regions since 1980 with M m i n = 2.0. Utilising the knowledge of cluster classification, the method has been adjusted to provide an earthquake declustering algorithm, which has been compared to existing methods. Its performance is comparable to established methodologies. The analysis of earthquake clustering statistics lead to various new and updated correlation functions, e.g. for ratios between mainshock and strongest aftershock and general aftershock activity metrics.

Parallel metatranscriptome analyses of host and symbiont gene expression in the gut of the termite Reticulitermes flavipes

PubMed Central

Tartar, Aurélien; Wheeler, Marsha M; Zhou, Xuguo; Coy, Monique R; Boucias, Drion G; Scharf, Michael E

2009-01-01

Background Termite lignocellulose digestion is achieved through a collaboration of host plus prokaryotic and eukaryotic symbionts. In the present work, we took a combined host and symbiont metatranscriptomic approach for investigating the digestive contributions of host and symbiont in the lower termite Reticulitermes flavipes. Our approach consisted of parallel high-throughput sequencing from (i) a host gut cDNA library and (ii) a hindgut symbiont cDNA library. Subsequently, we undertook functional analyses of newly identified phenoloxidases with potential importance as pretreatment enzymes in industrial lignocellulose processing. Results Over 10,000 expressed sequence tags (ESTs) were sequenced from the 2 libraries that aligned into 6,555 putative transcripts, including 171 putative lignocellulase genes. Sequence analyses provided insights in two areas. First, a non-overlapping complement of host and symbiont (prokaryotic plus protist) glycohydrolase gene families known to participate in cellulose, hemicellulose, alpha carbohydrate, and chitin degradation were identified. Of these, cellulases are contributed by host plus symbiont genomes, whereas hemicellulases are contributed exclusively by symbiont genomes. Second, a diverse complement of previously unknown genes that encode proteins with homology to lignase, antioxidant, and detoxification enzymes were identified exclusively from the host library (laccase, catalase, peroxidase, superoxide dismutase, carboxylesterase, cytochrome P450). Subsequently, functional analyses of phenoloxidase activity provided results that were strongly consistent with patterns of laccase gene expression. In particular, phenoloxidase activity and laccase gene expression are mostly restricted to symbiont-free foregut plus salivary gland tissues, and phenoloxidase activity is inducible by lignin feeding. Conclusion To our knowledge, this is the first time that a dual host-symbiont transcriptome sequencing effort has been conducted in a single termite species. This sequence database represents an important new genomic resource for use in further studies of collaborative host-symbiont termite digestion, as well as development of coevolved host and symbiont-derived biocatalysts for use in industrial biomass-to-bioethanol applications. Additionally, this study demonstrates that: (i) phenoloxidase activities are prominent in the R. flavipes gut and are not symbiont derived, (ii) expands the known number of host and symbiont glycosyl hydrolase families in Reticulitermes, and (iii) supports previous models of lignin degradation and host-symbiont collaboration in cellulose/hemicellulose digestion in the termite gut. All sequences in this paper are available publicly with the accession numbers FL634956-FL640828 (Termite Gut library) and FL641015-FL645753 (Symbiont library). PMID:19832970

Functional, interactive and critical health literacy: Varying relationships with control over care and number of GP visits.

PubMed

van der Heide, Iris; Heijmans, Monique; Schuit, A Jantine; Uiters, Ellen; Rademakers, Jany

2015-08-01

The aim of this study is to examine the extent to which functional, interactive and critical health literacy are associated with patients' perceived control over care and frequency of GP visits. Data from the Dutch 'National Panel of People with Chronic Illness or Disability' was used (N=2508). Health literacy was assessed by the Functional, Communicative and Critical Health Literacy measure. Perceived control over care was indicated by perceived ability to organize care, interact with providers and to perform self-care. By multivariate linear and logistic regression analyses, associations between health literacy and perceived control over care and subsequently frequency of GP visits were studied. Mainly interactive health literacy was associated with patients' perceived ability to organize care, interact with healthcare providers and perform self-care, whereas only functional health literacy was associated with number of GP visits. The results imply that some patients' may be less able to exert control over their care because of lower health literacy. Functional, interactive and critical health literacy vary in their relevance for patients' ability to exert control. Initiatives for strengthening patients' role in healthcare may be improved by paying attention to patients' health literacy, specifically functional and interactive health literacy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Grazing of leaf-associated Cercomonads (Protists: Rhizaria: Cercozoa) structures bacterial community composition and function.

PubMed

Flues, Sebastian; Bass, David; Bonkowski, Michael

2017-08-01

Preferential food selection in protists is well documented, but we still lack basic understanding on how protist predation modifies the taxonomic and functional composition of bacterial communities. We conducted feeding trials using leaf-associated cercomonad Cercozoa by incubating them on a standardized, diverse bacterial community washed from plant leaves. We used a shotgun metagenomics approach to investigate the taxonomic and functional changes of the bacterial community after five days protist predation on bacteria. Predation-induced shifts in bacterial community composition could be linked to phenotypic protist traits. Protist reproduction rate, morphological plasticity and cell speed were most important in determining bacterial community composition. Analyses of co-occurrence patterns showed less complex correlations between bacterial taxa in the protist-grazed treatments with a higher proportion of positive correlations than in non-grazed controls, suggesting that predation reduced the influence of strong competitors. Protist predation influenced 14 metabolic core functions including membrane transport from which type VI secretion systems were in particular upregulated. In view of the functional importance of bacterial communities in the phyllosphere and rhizosphere of plants, a more detailed understanding of predator-prey interactions, changes in microbial composition and function, and subsequent repercussions on plant performance are clearly required. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

Impulsive-antisocial psychopathic traits linked to increased volume and functional connectivity within prefrontal cortex.

PubMed

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-07-01

Psychopathy is a personality disorder characterized by callous lack of empathy, impulsive antisocial behavior, and criminal recidivism. Studies of brain structure and function in psychopathy have frequently identified abnormalities in the prefrontal cortex. However, findings have not yet converged to yield a clear relationship between specific subregions of prefrontal cortex and particular psychopathic traits. We performed a multimodal neuroimaging study of prefrontal cortex volume and functional connectivity in psychopathy, using a sample of adult male prison inmates (N = 124). We conducted volumetric analyses in prefrontal subregions, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. We found that overall psychopathy severity and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger prefrontal subregion volumes, particularly in the medial orbitofrontal cortex and dorsolateral prefrontal cortex. Furthermore, Factor 2 scores were also positively correlated with functional connectivity between several areas of the prefrontal cortex. The results were not attributable to age, race, IQ, substance use history, or brain volume. Collectively, these findings provide evidence for co-localized increases in prefrontal cortex volume and intra-prefrontal functional connectivity in relation to impulsive/antisocial psychopathic traits. © The Author (2017). Published by Oxford University Press.

Adolescent Substance Use Following Participation in a Universal Drug Prevention Program: Examining Relationships with Program Recall and Baseline Use Status

PubMed Central

Bavarian, Niloofar; Duncan, Robert; Lewis, Kendra M.; Miao, Alicia; Washburn, Isaac J.

2014-01-01

Background We examined whether adolescents receiving a universal, school-based, drug-prevention program in grade 7 varied, by student profile, in substance use behaviors post-program implementation. Profiles were a function of recall of program receipt and substance use at baseline. Methods We analyzed data from the Adolescent Substance Abuse Prevention Study, a large, geographically diverse, longitudinal school-based cluster-randomized controlled trial of the Take Charge of Your Life drug-prevention program. Profiles were created using self-reported substance use (pre-intervention) and program recall (post-intervention) at Grade 7. We first examined characteristics of each of the four profiles of treatment students who varied by program recall and baseline substance use. Using multilevel logistic regression analyses, we examined differences in the odds of substance use (alcohol, tobacco, and marijuana) among student profiles at the six additional study waves (Time 2 (Grade 7) through Time 7 (Grade 11)). Results Pearson’s chi-square tests showed sample characteristics varied by student profile. Multilevel logistic regression results were consistent across all examined substance use behaviors at all time points. Namely, as compared to students who had no baseline substance use and had program recall (No Use, Recall), each of the remaining three profiles (No Use, No Recall; Use, Recall; Use, No Recall) were more likely to engage in substance use. Post-hoc analyses showed that for the two sub-profiles of baseline substance users, there were only two observed, and inconsistent, differences in the odds of subsequent substance use by recall status. Conclusions Findings suggest that for students who were not baseline substance users, program recall significantly decreased the likelihood of subsequent substance use. For students who were baseline substance users, program recall did not generally influence subsequent substance use. Implications for school-based drug prevention programs are discussed. PMID:25148566

Adolescent Substance Use Following Participation in a Universal Drug Prevention Program: Examining Relationships With Program Recall and Baseline Use Status.

PubMed

Bavarian, Niloofar; Duncan, Robert; Lewis, Kendra M; Miao, Alicia; Washburn, Isaac J

2015-01-01

The study examined whether adolescents receiving a universal, school based, drug prevention program in Grade 7 varied, by student profile, in substance use behaviors post program implementation. Profiles were a function of recall of program receipt and substance use at baseline. A secondary analysis was conducted on data from the Adolescent Substance Abuse Prevention Study, a large, geographically diverse, longitudinal school-based cluster-randomized controlled trial of the Take Charge of Your Life drug prevention program. Profiles were created using self-reported substance use (preintervention) and program recall (postintervention) at Grade 7. First, characteristics of each of the 4 profiles of treatment students who varied by program recall and baseline substance use were explored. Then, multilevel logistic regression analyses were used to examine differences in the odds of substance use (alcohol, tobacco, and marijuana) among student profiles at the 6 additional study waves (Time 2 [Grade 7] through Time 7 [Grade 11]). Pearson's chi-square tests showed sample characteristics varied by student profile. Multilevel logistic regression results were consistent across all examined substance use behaviors at all time points. Namely, as compared with students who had no baseline substance use and had program recall (No Use, Recall), each of the remaining 3 profiles (No Use, No Recall; Use, Recall; Use, No Recall) were more likely to engage in substance use. Post hoc analyses showed that for the 2 subprofiles of baseline substance users, there were only 2 observed, and inconsistent, differences in the odds of subsequent substance use by recall status. Findings suggest that for students who were not baseline substance users, program recall significantly decreased the likelihood of subsequent substance use. For students who were baseline substance users, program recall did not generally influence subsequent substance use. Implications for school-based drug prevention programs are discussed.

Successful Aging in the Context of the Disablement Process: Working and Volunteering as Moderators on the Association Between Chronic Conditions and Subsequent Functional Limitations.

PubMed

Kail, Ben Lennox; Carr, Dawn C

2017-03-01

This study evaluated the successful aging model by assessing the impact of two forms of productive engagement-working and volunteering-as potential interventions in the process of disablement. The Health and Retirement Study was used to (a) estimate two-stage selection equations of (i) currently working part time and full time and (ii) currently volunteering less than 100 hours and volunteering 100 hours or more per year (net of chronic health problems) and (b) assess whether, net of selection, working, and volunteering moderate the association between chronic conditions and subsequent functional limitations. Chronic conditions were associated with elevated levels of subsequent functional limitations, whereas both working and volunteering were associated with lower levels of subsequent functional limitations. Moreover, workers and volunteers of less than 100 hours per year experienced a reduction in the association of chronic conditions on subsequent functional limitations. This research highlights the role of productive engagement as a key element in successful aging. Not only do work and volunteering have direct associations with health outcomes themselves, but they also act as potential interventions in the process of disablement by attenuating the way in which chronic conditions are translated into subsequent functional limitations. This suggests that (a) future research should apply successful aging models to health processes as well as health outcomes and (b) policy makers should support social institutions that foster late-life productive engagement. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework.

PubMed

Zhuravlev, Pavel I; Papoian, Garegin A

2010-08-01

Energy landscape theories have provided a common ground for understanding the protein folding problem, which once seemed to be overwhelmingly complicated. At the same time, the native state was found to be an ensemble of interconverting states with frustration playing a more important role compared to the folding problem. The landscape of the folded protein - the native landscape - is glassier than the folding landscape; hence, a general description analogous to the folding theories is difficult to achieve. On the other hand, the native basin phase volume is much smaller, allowing a protein to fully sample its native energy landscape on the biological timescales. Current computational resources may also be used to perform this sampling for smaller proteins, to build a 'topographical map' of the native landscape that can be used for subsequent analysis. Several major approaches to representing this topographical map are highlighted in this review, including the construction of kinetic networks, hierarchical trees and free energy surfaces with subsequent structural and kinetic analyses. In this review, we extensively discuss the important question of choosing proper collective coordinates characterizing functional motions. In many cases, the substates on the native energy landscape, which represent different functional states, can be used to obtain variables that are well suited for building free energy surfaces and analyzing the protein's functional dynamics. Normal mode analysis can provide such variables in cases where functional motions are dictated by the molecule's architecture. Principal component analysis is a more expensive way of inferring the essential variables from the protein's motions, one that requires a long molecular dynamics simulation. Finally, the two popular models for the allosteric switching mechanism, 'preexisting equilibrium' and 'induced fit', are interpreted within the energy landscape paradigm as extreme points of a continuum of transition mechanisms. Some experimental evidence illustrating each of these two models, as well as intermediate mechanisms, is presented and discussed.

Novel ex vivo culture method for human monocytes uses shear flow to prevent total loss of transendothelial diapedesis function.

PubMed

Tsubota, Yoshiaki; Frey, Jeremy M; Raines, Elaine W

2014-01-01

Monocyte recruitment to inflammatory sites and their transendothelial migration into tissues are critical to homeostasis and pathogenesis of chronic inflammatory diseases. However, even short-term suspension culture of primary human monocytes leads to phenotypic changes. In this study, we characterize the functional effects of ex vivo monocyte culture on the steps involved in monocyte transendothelial migration. Our data demonstrate that monocyte diapedesis is impaired by as little as 4 h culture, and the locomotion step is subsequently compromised. After 16 h in culture, monocyte diapedesis is irreversibly reduced by ∼90%. However, maintenance of monocytes under conditions mimicking physiological flow (5-7.5 dyn/cm²) is sufficient to reduce diapedesis impairment significantly. Thus, through the application of shear during ex vivo culture of monocytes, our study establishes a novel protocol, allowing functional analyses of monocytes not currently possible under static culture conditions. These data further suggest that monocyte-based therapeutic applications may be measurably improved by alteration of ex vivo conditions before their use in patients.

Transactional Relations Between Marital Functioning and Depressive Symptoms

PubMed Central

Kouros, Chrystyna D.; Cummings, E. Mark

2012-01-01

The present study investigated dynamic, longitudinal associations between depressive symptoms and marital processes. Two hundred ninety-six couples reported on marital satisfaction, marital conflict, and depressive symptoms yearly for three years. Observational measures of marital conflict were also collected. Results suggested that different domains of marital functioning related to husbands’ versus wives’ symptoms. For husbands, transactional relations between marital satisfaction and depressive symptoms were identified: high levels of depressive symptoms predicted subsequent decreases in marital satisfaction, and decreased marital satisfaction predicted subsequent elevations in symptoms over time. For wives, high levels of marital conflict predicted subsequent elevations in symptoms over time. Cross-partner results indicated that husbands’ depressive symptoms were also related to subsequent declines in wives’ marital satisfaction. Results are discussed with regard to theoretical perspectives on the marital functioning-depression link and directions for future research are outlined. PMID:21219284

Influence of a cyclic combination chemotherapeutic protocol on primary haemostasis in dogs suffering from malignant lymphoma.

PubMed

Eberle, N; Mischke, R

2010-03-01

The purpose of this study was to examine the influence of cyclic combination chemotherapy on primary haemostasis in dogs with malignant lymphoma. Seventeen dogs receiving cytostatic treatment for high-grade lymphoma were included in the study. The dogs were treated with a Madison-Wisconsin derived protocol, which included asparaginase, vincristine, doxorubicin and prednisolone. At different time points during the first 4 weeks of induction, platelet count, capillary bleeding time, analysis of the platelet function using the platelet function analyser PFA-100, and platelet aggregation by the Born-method were measured. The most obvious changes were found for median values of the platelet count, which increased significantly from 210,000/microL before induction to 349,000/microL during the second week of induction (P=0.0010). Median platelet count subsequently decreased by the fourth week of treatment (Friedman-test: P<0.0001). None of the parameters of platelet function (capillary bleeding time, automatic platelet function analysis, aggregation maximum) showed significant changes with time (P>0.05, Friedman-test). The results did not suggest that significant platelet dysfunction was induced by the chemotherapeutic protocol used in the study. 2009 Elsevier Ltd. All rights reserved.

High fluorescence emission of carboxylic acid functionalized polystyrene/BaTiO{sub 3} nanocomposites and rare earth metal complexes: Preparation and characterization

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

Cao, X. T.; Showkat, A. M.; Wang, Z.

2015-03-30

Noble fluorescence nanocomposite compound based on barium titanate nanoparticles (BTO), polystyrene (PSt), and terbium ion (Tb{sup 3+}) was synthesized by a combination of surface-initiated reversible addition-fragmentation chain transfer (RAFT) polymerization, Friedel-Crafts alkylation reaction and coordinate chemistry. Initially, a modification of surface of BTO was conducted by an exchange process with S-benzyl S’-trimethoxysilylpropyltrithiocarbonate to create macro-initiator for polymerization of styrene. Subsequently, aryl carboxylic acid functionalized polystyrene grafted barium titanate (BTO-g-PSt-COOH) was generated by substitution reaction between 4-(Chloromethyl) benzoic acid and PSt chains. The coordination of the nanohybrids with Tb{sup 3+} ions afforded fluorescent Tb{sup 3+} tagged aryl carboxylic acid functionalized polystyrenemore » grafted barium titanate (BTO-g-PSt-Tb{sup 3+}) complexes. Structure, morphology, and fluorescence properties of nanohybrid complexes were investigated by respective physical and spectral studies. FT-IR and SEM analyses confirmed the formation of BTO-g-PSt-Tb{sup 3+}nanohybrids. Furthermore, TGA profiles demonstrated the grafting of aryl carboxylic acid functionalized polystyrene on BTO surface. Optical properties of BTO-g-PSt-Tb{sup 3+} complexes were investigated by fluorescence spectroscopy.« less

Systematic analyses of the ultraviolet radiation resistance-associated gene product (UVRAG) protein interactome by tandem affinity purification.

PubMed

Son, Ji-Hye; Hwang, Eurim C; Kim, Joungmok

2016-03-01

Ultraviolet radiation resistance-associated gene product (UVRAG) was originally identified as a protein involved in cellular responses to UV irradiation. Subsequent studies have demonstrated that UVRAG plays as an important role in autophagy, a lysosome-dependent catabolic program, as a part of a pro-autophagy PIK3C3/VPS34 lipid kinase complex. Several recent studies have shown that UVRAG is also involved in autophagy-independent cellular functions, such as DNA repair/stability and vesicular trafficking/fusion. Here, we examined the UVRAG protein interactome to obtain information about its functional network. To this end, we screened UVRAG-interacting proteins using a tandem affinity purification method coupled with MALDI-TOF/MS analysis. Our results demonstrate that UVRAG interacts with various proteins involved in a wide spectrum of cellular functions, including genome stability, protein translational elongation, protein localization (trafficking), vacuole organization, transmembrane transport as well as autophagy. Notably, the interactome list of high-confidence UVRAG-interacting proteins is enriched for proteins involved in the regulation of genome stability. Our systematic UVRAG interactome analysis should provide important clues for understanding a variety of UVRAG functions.

Densification of a-IGZO with low-temperature annealing for flexible electronics applications

NASA Astrophysics Data System (ADS)

Troughton, J. G.; Downs, P.; Price, R.; Atkinson, D.

2017-01-01

Amorphous InGaZnO (a-IGZO) thin-film transistors are a leading contender for active channel materials in next generation flat panel displays and flexible electronics. Improved electronic functionality has been linked to the increased density of a-IGZO, and while much work has looked at high-temperature processes, studies at temperatures compatible with flexible substrates are needed. Here, compositional and structural analyses show that short term, low-temperature annealing (<6 h) can increase the density of sputtered a-IGZO by up to 5.6% for temperatures below 300 °C, which is expected to improve the transistor performance, while annealing for longer times leads to a subsequent decrease in density due to oxygen absorption.

Clinically relevant advances in on-chip affinity-based electrophoresis and electrochromatography.

PubMed

Hou, Chenlu; Herr, Amy E

2008-08-01

Clinical and point-of-care disease diagnostics promise to play an important role in personalized medicine, new approaches to global health, and health monitoring. Emerging instrument platforms based on lab-on-a-chip technology can confer performance advantages successfully exploited in electrophoresis and electrochromatography to affinity-based electrokinetic separations. This review surveys lab-on-a-chip diagnostic developments in affinity-based electrokinetic separations for quantitation of proteins, integration of preparatory functions needed for subsequent analysis of diverse biological samples, and initial forays into multiplexed analyses. The technologies detailed here underpin new clinical and point-of-care diagnostic strategies. The techniques and devices promise to advance translation of until now laboratory-based sample preparation and analytical assays to near-patient settings.

Still searching for the engram

PubMed Central

Eichenbaum, Howard

2016-01-01

For nearly a century neurobiologists have searched for the engram - the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories. PMID:26944423

Inducible antisense suppression of glycolate oxidase reveals its strong regulation over photosynthesis in rice.

PubMed

Xu, Huawei; Zhang, Jianjun; Zeng, Jiwu; Jiang, Linrong; Liu, Ee; Peng, Changlian; He, Zhenghui; Peng, Xinxiang

2009-01-01

Photorespiration is one of the most intensively studied topics in plant biology. While a number of mutants deficient in photorespiratory enzymes have been identified and characterized for their physiological functions, efforts on glycolate oxidase (GLO; EC 1.1.3.15) have not been so successful. This is a report about the generation of transgenic rice (Oryza sativa L.) plants carrying a GLO antisense gene driven by an estradiol-inducible promoter, which allowed for controllable suppressions of GLO and its detailed functional analyses. The GLO-suppressed plants showed typical photorespiration-deficient phenotypes. More intriguingly, it was found that a positive and linear correlation existed between GLO activities and the net photosynthetic rates (P(N)), and photoinhibition subsequently occurred once P(N) reduction surpassed 60%, indicating GLO can exert a strong regulation over photosynthesis. Various expression analyses identified that Rubisco activase was transcriptionally suppressed in the GLO-suppressed plants, consistent with the decreased Rubisco activation states. While the substrate glycolate accumulated substantially, few changes were observed for the product glyoxylate, and for some other downstream metabolites or genes as well in the transgenic plants. Further analyses revealed that isocitrate lyase and malate synthase, two key enzymes in the glyoxylate cycle, were highly up-regulated under GLO deficiency. Taken together, the results suggest that GLO is a typical photorespiratory enzyme and that it can exert a strong regulation over photosynthesis, possibly through a feed-back inhibition on Rubisco activase, and that the glyoxylate cycle may be partially activated to compensate for the photorespiratory glyoxylate when GLO is suppressed in rice.

Healthy ageing in the Nun Study: definition and neuropathologic correlates.

PubMed

Tyas, Suzanne L; Snowdon, David A; Desrosiers, Mark F; Riley, Kathryn P; Markesbery, William R

2007-11-01

Although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. To develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. The biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing.

Healthy ageing in the Nun Study: definition and neuropathologic correlates

PubMed Central

Tyas, Suzanne L.; Snowdon, David A.; Desrosiers, Mark F.; Riley, Kathryn P.; Markesbery, William R.

2008-01-01

Background although the concept of healthy ageing has stimulated considerable interest, no generally accepted definition has been developed nor has its biological basis been determined. Objective to develop a definition of healthy ageing and investigate its association with longevity and neuropathology. Methods analyses were based on cognitive, physical, and post-mortem assessments from 1991 to 1998 in the Nun Study, a longitudinal study of ageing in participants 75+ years at baseline. We defined three mutually exclusive levels of healthy ageing (excellent, very good, and good) based on measures of global cognitive function, short-term memory, basic and instrumental activities of daily living, and self-rated function. Mortality analyses were based on 636 participants; neuropathologic analyses were restricted to 221 who had died and were autopsied. Results only 11% of those meeting criteria for the excellent level of healthy ageing at baseline subsequently died, compared with 24% for the very good, 39% for the good, and 60% for the remaining participants. Survival curves showed significantly greater longevity with higher levels of healthy ageing. The risk of not attaining healthy ageing, adjusted for age, increased two-fold in participants with brain infarcts alone, six-fold in those with Alzheimer neuropathology alone, and more than thirteen-fold in those with both brain infarcts and Alzheimer neuropathology. Conclusions the biological validity of our definition of healthy ageing is supported by its strong association with mortality and longevity. Avoiding Alzheimer and stroke neuropathology is critical to the maintenance of healthy ageing, and the presence of both pathologies dramatically decreases the likelihood of healthy ageing. PMID:17906306

How do cardiorespiratory fitness improvements vary with physical training modality in heart failure patients? A quantitative guide

PubMed Central

Smart, Neil A

2013-01-01

BACKGROUND: Peak oxygen consumption (VO2) is the gold standard measure of cardiorespiratory fitness and a reliable predictor of survival in chronic heart failure patients. Furthermore, any form of physical training usually improves cardiorespiratory fitness, although the magnitude of improvement in peak VO2 may vary across different training prescriptions. OBJECTIVE: To quantify, and subsequently rank, the magnitude of improvement in peak VO2 for different physical training prescriptions using data from published meta-analyses and randomized controlled trials. METHODS: Prospective randomized controlled parallel trials and meta-analyses of exercise training in chronic heart failure patients that provided data on change in peak VO2 for nine a priori comparative analyses were examined. RESULTS: All forms of physical training were beneficial, although the improvement in peak VO2 varied with modality. High-intensity interval exercise yielded the largest increase in peak VO2, followed in descending order by moderate-intensity aerobic exercise, functional electrical stimulation, inspiratory muscle training, combined aerobic and resistance training, and isolated resistance training. With regard to setting, the present study was unable to determine whether outpatient or unsupervised home exercise provided greater benefits in terms of peak VO2 improvment. CONCLUSIONS: Interval exercise is not suitable for all patients, especially the high-intensity variety; however, when indicated, this form of exercise should be adopted to optimize peak VO2 adaptations. Other forms of activity, such as functional electrical stimulation, may be more appropriate for patients who are not capable of high-intensity interval training, especially for severely deconditioned patients who are initially unable to exercise. PMID:24294043

Changed Hub and Corresponding Functional Connectivity of Subgenual Anterior Cingulate Cortex in Major Depressive Disorder

PubMed Central

Wu, Huawang; Sun, Hui; Xu, Jinping; Wu, Yan; Wang, Chao; Xiao, Jing; She, Shenglin; Huang, Jianwei; Zou, Wenjin; Peng, Hongjun; Lu, Xiaobing; Huang, Guimao; Jiang, Tianzi; Ning, Yuping; Wang, Jiaojian

2016-01-01

Major depressive disorder (MDD) is one of the most prevalent mental disorders. In the brain, the hubs of the brain network play a key role in integrating and transferring information between different functional modules. However, whether the changed pattern in functional network hubs contributes to the onset of MDD remains unclear. Using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory methods, we investigated whether alterations of hubs can be detected in MDD. First, we constructed the whole-brain voxel-wise functional networks and calculated a functional connectivity strength (FCS) map in each subject in 34 MDD patients and 34 gender-, age- and education level-matched healthy controls (HCs). Next, the two-sample t-test was applied to compare the FCS maps between HC and MDD patients and identified significant decrease of FCS in subgenual anterior cingulate cortex (sgACC) in MDD patients. Subsequent functional connectivity analyses of sgACC showed disruptions in functional connectivity with posterior insula, middle and inferior temporal gyrus, lingual gyrus and cerebellum in MDD patients. Furthermore, the changed FCS of sgACC and functional connections to sgACC were significantly correlated with the Hamilton Depression Rating Scale (HDRS) scores in MDD patients. The results of the present study revealed the abnormal hub of sgACC and its corresponding disrupted frontal-limbic-visual cognitive-cerebellum functional networks in MDD. These findings may provide a new insight for the diagnosis and treatment of MDD. PMID:28018183

Development of an open-path gas analyser for plume detection in security applications

NASA Astrophysics Data System (ADS)

Hay, Kenneth G.; Norberg, Ola; Normand, Erwan; Önnerud, Hans; Black, Paul

2017-04-01

We present here an open-path analyser, initially intended for security applications, specifically for the detection of gas plumes from illicit improvised explosive device (IED) manufacturing. Subsequently, the analysers were adapted for methane measurement and used to investigate its applicability for leak detection in different scenarios (e.g. unconventional gas extraction sites). Preliminary results showed consistent measurements of gas plumes in the open path.

The Tubular Sheaths Encasing Methanosaeta thermophila Filaments Are Functional Amyloids.

PubMed

Dueholm, Morten S; Larsen, Poul; Finster, Kai; Stenvang, Marcel R; Christiansen, Gunna; Vad, Brian S; Bøggild, Andreas; Otzen, Daniel E; Nielsen, Per Halkjær

2015-08-14

Archaea are renowned for their ability to thrive in extreme environments, although they can be found in virtually all habitats. Their adaptive success is linked to their unique cell envelopes that are extremely resistant to chemical and thermal denaturation and that resist proteolysis by common proteases. Here we employ amyloid-specific conformation antibodies and biophysical techniques to show that the extracellular cell wall sheaths encasing the methanogenic archaea Methanosaeta thermophila PT are functional amyloids. Depolymerization of sheaths and subsequent MS/MS analyses revealed that the sheaths are composed of a single major sheath protein (MspA). The amyloidogenic nature of MspA was confirmed by in vitro amyloid formation of recombinant MspA under a wide range of environmental conditions. This is the first report of a functional amyloid from the archaeal domain of life. The amyloid nature explains the extreme resistance of the sheath, the elastic properties that allow diffusible substrates to penetrate through expandable hoop boundaries, and how the sheaths are able to split and elongate outside the cell. The archaeal sheath amyloids do not share homology with any of the currently known functional amyloids and clearly represent a new function of the amyloid protein fold. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

MRI correlates of interaction between gender and expressive suppression among the Chinese population.

PubMed

Wang, Kangcheng; Huang, Hui; Chen, Li; Hou, Xin; Zhang, Yong; Yang, Junyi; Hao, Xin; Qiu, Jiang

2017-04-07

Expressive suppression is a kind of emotion regulation strategies by suppressing behaviors related to emotional responding. Despite the amount of behavioral research on expressive suppression, the structural and functional mechanisms underlying the interaction between gender and expressive suppression in Chinese healthy subjects have remained unknown. In the current study, we assessed the levels of expressive suppression and acquired the structural and functional imaging data from 273 Chinese individuals. A nearly automatic cortical processing technique was used to calculate cortical thickness for each subject. The results from cortical thickness analyses revealed a significant interaction between gender and expressive suppression in the superior frontal gyrus. Then, we conducted the whole-brain functional connectivity analysis with the seed of the superior frontal gyrus to explore the functionally related regions of brain. Subsequent analysis of the interaction between gender and expressive suppression indicated a significant functional connectivity between the superior frontal gyrus and default mode network (DMN) core regions, including the medial prefrontal cortex, precuneus and parahippocampal gyrus. Our results provided the robust empirical evidence illustrating the role of the superior frontal gyrus and DMN in gender difference of expressive suppression among the Chinese population. These findings might have implications for understanding gender difference in emotion processing and regulation. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Technical Advance: Live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung

PubMed Central

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G.; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-01-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. PMID:24899587

Brain structure and function correlates of cognitive subtypes in schizophrenia.

PubMed

Geisler, Daniel; Walton, Esther; Naylor, Melissa; Roessner, Veit; Lim, Kelvin O; Charles Schulz, S; Gollub, Randy L; Calhoun, Vince D; Sponheim, Scott R; Ehrlich, Stefan

2015-10-30

Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Virtual reconstruction of modern and fossil hominoid crania: consequences of reference sample choice.

PubMed

Senck, Sascha; Bookstein, Fred L; Benazzi, Stefano; Kastner, Johann; Weber, Gerhard W

2015-05-01

Most hominin cranial fossils are incomplete and require reconstruction prior to subsequent analyses. Missing data can be estimated by geometric morphometrics using information from complete specimens, for example, by using thin-plate splines. In this study, we estimate missing data in several virtually fragmented models of hominoid crania (Homo, Pan, Pongo) and fossil hominins (e.g., Australopithecus africanus, Homo heidelbergensis). The aim is to investigate in which way different references influence estimations of cranial shape and how this information can be employed in the reconstruction of fossils. We used a sample of 64 three-dimensional digital models of complete human, chimpanzee, and orangutan crania and a set of 758 landmarks and semilandmarks. The virtually knocked out neurocranial and facial areas that were reconstructed corresponded to those of a real case found in A.L. 444-2 (A. afarensis) cranium. Accuracy of multiple intraspecies and interspecies reconstructions was computed as the maximum square root of the mean squared difference between the original and the reconstruction (root mean square). The results show that the uncertainty in reconstructions is a function of both the geometry of the knockout area and the dissimilarity between the reference sample and the specimen(s) undergoing reconstruction. We suggest that it is possible to estimate large missing cranial areas if the shape of the reference is similar enough to the shape of the specimen reconstructed, though caution must be exercised when employing these reconstructions in subsequent analyses. We provide a potential guide for the choice of the reference by means of bending energy. © 2015 Wiley Periodicals, Inc.

Long-term effects of routine morphine infusion in mechanically ventilated neonates on children's functioning: five-year follow-up of a randomized controlled trial.

PubMed

de Graaf, Joke; van Lingen, Richard A; Simons, Sinno H P; Anand, Kanwaljeet J S; Duivenvoorden, Hugo J; Weisglas-Kuperus, Nynke; Roofthooft, Daniella W E; Groot Jebbink, Liesbeth J M; Veenstra, Ravian R; Tibboel, Dick; van Dijk, Monique

2011-06-01

Newborns on ventilatory support often receive morphine to induce analgesia. Animal experiments suggest that this may impair subsequent cognitive and behavioral development. There are sparse human data on long-term effects of neonatal morphine. We aimed to investigate the effects of continuous morphine administered in the neonatal period on the child's functioning. We conducted a follow-up study among 5-year-olds who, as mechanically ventilated neonates, had participated in a placebo-controlled trial on effects of morphine administration on pain and neurologic outcome. They were now tested on intelligence, visual motor integration, behavior, chronic pain, and health-related quality of life. Univariate analyses showed significantly lower overall intelligence quotient (IQ) scores for children who earlier had received morphine, that is, mean 94 (SD 14.5) versus 100 (SD 12.9) for those who received placebo (P = 0.049). Other between-group differences in outcomes were not found. The statistical difference disappeared after correction for treatment condition, open-label morphine consumption over the first 28 days, and a propensity score for clinically relevant co-variables in multiple regression analyses. However, scores on one IQ subtest, "visual analysis," were significantly negatively related to having received morphine and to open-label morphine consumption the first 28 days. The finding of a significant effect of morphine on the "visual analysis" IQ subtest calls for follow-up at a later age focusing on the higher-order neurocognitive functions. Morphine received in the neonatal period has negative effects on the child's cognitive functioning at the age of 5 years which warrants follow-up at a later age. Copyright © 2011 International Association for the Study of Pain. All rights reserved.

Consumption of Bifidobacterium lactis Bi-07 by healthy elderly adults enhances phagocytic activity of monocytes and granulocytes.

PubMed

Maneerat, Sujira; Lehtinen, Markus J; Childs, Caroline E; Forssten, Sofia D; Alhoniemi, Esa; Tiphaine, Milin; Yaqoob, Parveen; Ouwehand, Arthur C; Rastall, Robert A

2013-01-01

Elderly adults have alterations in their gut microbiota and immune functions that are associated with higher susceptibility to infections and metabolic disorders. Probiotics and prebiotics, and their synbiotic combinations are food supplements that have been shown to improve both gut and immune function. The objective of this randomised, double-blind, placebo-controlled, cross-over human clinical trial was to study immune function and the gut microbiota in healthy elderly adults. Volunteers (n 37) consumed prebiotic galacto-oligosaccharides (GOS; 8 g/d), probiotic Bifidobacterium lactis Bi-07 (Bi-07; 10(9) colony-forming units/d), their combination (Bi-07 + GOS) and maltodextrin control (8 g/d) in four 3-week periods separated by 4-week wash-out periods. Immune function was analysed by determining the phagocytic and oxidative burst activity of monocytes and granulocytes, whole-blood response to lipopolysaccharide, plasma chemokine concentrations and salivary IgA levels. Gut microbiota composition and faecal SCFA content were determined using 16S ribosomal RNA fluorescence in situ hybridisation and HPLC, respectively. Primary statistical analyses indicated the presence of carry-over effects and thus measurements from only the first supplementation period were considered valid. Subsequent statistical analysis showed that consumption of Bi-07 improved the phagocytic activity of monocytes (P < 0·001) and granulocytes (P = 0·02). Other parameters were unchanged. We have for the first time shown that the probiotic Bi-07 may provide health benefits to elderly individuals by improving the phagocytic activity of monocytes and granulocytes. The present results also suggest that in the elderly, the effects of some probiotics and prebiotics may last longer than in adults.

The bilaterian head patterning gene six3/6 controls aboral domain development in a cnidarian.

PubMed

Sinigaglia, Chiara; Busengdal, Henriette; Leclère, Lucas; Technau, Ulrich; Rentzsch, Fabian

2013-01-01

The origin of the bilaterian head is a fundamental question for the evolution of animal body plans. The head of bilaterians develops at the anterior end of their primary body axis and is the site where the brain is located. Cnidarians, the sister group to bilaterians, lack brain-like structures and it is not clear whether the oral, the aboral, or none of the ends of the cnidarian primary body axis corresponds to the anterior domain of bilaterians. In order to understand the evolutionary origin of head development, we analysed the function of conserved genetic regulators of bilaterian anterior development in the sea anemone Nematostella vectensis. We show that orthologs of the bilaterian anterior developmental genes six3/6, foxQ2, and irx have dynamic expression patterns in the aboral region of Nematostella. Functional analyses reveal that NvSix3/6 acts upstream of NvFoxQ2a as a key regulator of the development of a broad aboral territory in Nematostella. NvSix3/6 initiates an autoregulatory feedback loop involving positive and negative regulators of FGF signalling, which subsequently results in the downregulation of NvSix3/6 and NvFoxQ2a in a small domain at the aboral pole, from which the apical organ develops. We show that signalling by NvFGFa1 is specifically required for the development of the apical organ, whereas NvSix3/6 has an earlier and broader function in the specification of the aboral territory. Our functional and gene expression data suggest that the head-forming region of bilaterians is derived from the aboral domain of the cnidarian-bilaterian ancestor.

The Bilaterian Head Patterning Gene six3/6 Controls Aboral Domain Development in a Cnidarian

PubMed Central

Sinigaglia, Chiara; Busengdal, Henriette; Leclère, Lucas; Technau, Ulrich; Rentzsch, Fabian

2013-01-01

The origin of the bilaterian head is a fundamental question for the evolution of animal body plans. The head of bilaterians develops at the anterior end of their primary body axis and is the site where the brain is located. Cnidarians, the sister group to bilaterians, lack brain-like structures and it is not clear whether the oral, the aboral, or none of the ends of the cnidarian primary body axis corresponds to the anterior domain of bilaterians. In order to understand the evolutionary origin of head development, we analysed the function of conserved genetic regulators of bilaterian anterior development in the sea anemone Nematostella vectensis. We show that orthologs of the bilaterian anterior developmental genes six3/6, foxQ2, and irx have dynamic expression patterns in the aboral region of Nematostella. Functional analyses reveal that NvSix3/6 acts upstream of NvFoxQ2a as a key regulator of the development of a broad aboral territory in Nematostella. NvSix3/6 initiates an autoregulatory feedback loop involving positive and negative regulators of FGF signalling, which subsequently results in the downregulation of NvSix3/6 and NvFoxQ2a in a small domain at the aboral pole, from which the apical organ develops. We show that signalling by NvFGFa1 is specifically required for the development of the apical organ, whereas NvSix3/6 has an earlier and broader function in the specification of the aboral territory. Our functional and gene expression data suggest that the head-forming region of bilaterians is derived from the aboral domain of the cnidarian-bilaterian ancestor. PMID:23483856

Relationships between Circulating Urea Concentrations and Endometrial Function in Postpartum Dairy Cows.

PubMed

Cheng, Zhangrui; Oguejiofor, Chike F; Swangchan-Uthai, Theerawat; Carr, Susan; Wathes, D Claire

2015-08-14

Both high and low circulating urea concentrations, a product of protein metabolism, are associated with decreased fertility in dairy cows through poorly defined mechanisms. The rate of involution and the endometrial ability to mount an adequate innate immune response after calving are both critical for subsequent fertility. Study 1 used microarray analysis to identify genes whose endometrial expression 2 weeks postpartum correlated significantly with the mean plasma urea per cow, ranging from 3.2 to 6.6 mmol/L. The biological functions of 781 mapped genes were analysed using Ingenuity Pathway Analysis. These were predominantly associated with tissue turnover (e.g., BRINP1, FOXG1), immune function (e.g., IL17RB, CRISPLD2), inflammation (e.g., C3, SERPINF1, SERPINF2) and lipid metabolism (e.g., SCAP, ACBD5, SLC10A). Study 2 investigated the relationship between urea concentration and expression of 6 candidate genes (S100A8, HSP5A, IGF1R, IL17RB, BRINP1, CRISPLD2) in bovine endometrial cell culture. These were treated with 0, 2.5, 5.0 or 7.5 mmol/L urea, equivalent to low, medium and high circulating values with or without challenge by bacterial lipopolysaccharide (LPS). LPS increased S100A8 expression as expected but urea treatment had no effect on expression of any tested gene. Examination of the genes/pathways involved suggests that plasma urea levels may reflect variations in lipid metabolism. Our results suggest that it is the effects of lipid metabolism rather than the urea concentration which probably alter the rate of involution and innate immune response, in turn influencing subsequent fertility.

Functional electrospun membranes

NASA Astrophysics Data System (ADS)

Ognibene, G.; Fragalà, M. E.; Cristaldi, D. A.; Blanco, I.; Cicala, G.

2016-05-01

In this study we combined electrospun PES nanofibers with ZnO nanostructures in order to obtain a hierarchical nanostructured hybrid material to be use for active water filtration membranes. It benefits of flexibility and high surface area of the polymeric nanofibers as well as of additional functionalities of ZnOnanostructures. First, randomly oriented nanofibers with diameters of 716nm ±365 nm were electrospun on a glass fibers substrate from a solution of PES and DMF-TOL(1:1). ZnO nanorods were grown onto the surface of electrospun PES fibers by a Chemical Bath Deposition (CBD) process. It was preceed by a seeding process necessary to form nucleation sites for the subsequent radially aligned growth of ZnO nanowires. The morfology of the fibers and the effect of the seeding time have been analysed by SEM. The amount of ZnO nanowires grown over electrospun nanofibers was determined as 45% by weight. The high purity and crystallinity of the asobtained products are confirmed by XRD since all reflection peaks can be indexed to hexagonal wurtzite ZnO.

microRNA Expression Profiling: Technologies, Insights, and Prospects.

PubMed

Roden, Christine; Mastriano, Stephen; Wang, Nayi; Lu, Jun

2015-01-01

Since the early days of microRNA (miRNA) research, miRNA expression profiling technologies have provided important tools toward both better understanding of the biological functions of miRNAs and using miRNA expression as potential diagnostics. Multiple technologies, such as microarrays, next-generation sequencing, bead-based detection system, single-molecule measurements, and quantitative RT-PCR, have enabled accurate quantification of miRNAs and the subsequent derivation of key insights into diverse biological processes. As a class of ~22 nt long small noncoding RNAs, miRNAs present unique challenges in expression profiling that require careful experimental design and data analyses. We will particularly discuss how normalization and the presence of miRNA isoforms can impact data interpretation. We will present one example in which the consideration in data normalization has provided insights that helped to establish the global miRNA expression as a tumor suppressor. Finally, we discuss two future prospects of using miRNA profiling technologies to understand single cell variability and derive new rules for the functions of miRNA isoforms.

Common extensor origin release in recalcitrant lateral epicondylitis - role justified?

PubMed Central

2010-01-01

The aim of our study was to analyse the efficacy of operative management in recalcitrant lateral epicondylitis of elbow. Forty patients included in this study were referred by general practitioners with a diagnosis of tennis elbow to the orthopaedic department at a district general hospital over a five year period. All had two or more steroid injections at the tender spot, without permanent relief of pain. All subsequently underwent simple fasciotomy of the extensor origin. Of forty patients thirty five had improvement in pain and function, two had persistent symptoms and three did not perceive any improvement. Twenty five had excellent, ten had well, two had fair and three had poor outcomes (recurrent problem; pain at rest and night). Two patients underwent revision surgery. Majority of the patients had improvement in pain and function following operative treatment. In this study, an extensor fasciotomy was demonstrated to be an effective treatment for refractory chronic lateral epicondylitis; however, further studies are warranted. PMID:20459701

Commentary: On the Importance of Early Life Cognitive Abilities in Shaping Later Life Outcomes.

PubMed

Hofer, Scott M; Clouston, Sean

2014-01-01

Early life cognitive ability is likely to be dynamically related to life course factors including educational attainment, occupational outcomes, health behaviors, activities, health, and subsequent cognitive health. Disentangling the selective and causal processes contributing to cognitive functioning across the lifespan is challenging and requires long-term investments in longitudinal data. We discuss results from several analyses using data from the Individual Development and Adaptation longitudinal research program (Bergman, 2000; Magnusson, 1988) that provide fresh insights into the relation of early life cognition, particularly high levels of cognitive capabilities, to educational achievement, emotional adjustment, and career success. These papers and the longitudinal data provide a remarkable window into the development and impacts of cognition, and high cognitive functioning, on a variety of important life outcomes that we hope will continue to inform us about additional outcomes in middle life, transition to retirement, and cognition and health in later years and to robustly examine how the early years matter across the whole lifespan.

The link between social cognition and self-referential thought in the medial prefrontal cortex.

PubMed

Mitchell, Jason P; Banaji, Mahzarin R; Macrae, C Neil

2005-08-01

The medial prefrontal cortex (mPFC) has been implicated in seemingly disparate cognitive functions, such as understanding the minds of other people and processing information about the self. This functional overlap would be expected if humans use their own experiences to infer the mental states of others, a basic postulate of simulation theory. Neural activity was measured while participants attended to either the mental or physical aspects of a series of other people. To permit a test of simulation theory's prediction that inferences based on self-reflection should only be made for similar others, targets were subsequently rated for their degree of similarity to self. Parametric analyses revealed a region of the ventral mPFC--previously implicated in self-referencing tasks--in which activity correlated with perceived self/other similarity, but only for mentalizing trials. These results suggest that self-reflection may be used to infer the mental states of others when they are sufficiently similar to self.

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

PubMed

Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

Design and characterization of biofunctional magnetic porous silicon flakes.

PubMed

Muñoz Noval, A; García, R; Ruiz Casas, D; Losada Bayo, D; Sánchez Vaquero, V; Torres Costa, V; Martín Palma, R J; García, M A; García Ruiz, J P; Serrano Olmedo, J J; Muñoz Negrete, J F; del Pozo Guerrero, F; Manso Silván, M

2013-04-01

Magnetic porous silicon flakes (MPSF) were obtained from mesoporous silicon layers formed by multi-step anodization and subsequent composite formation with Fe oxide nanoparticles by thermal annealing. The magnetic nanoparticles adhered to the surface and penetrated inside the pores. Their structure evolved as a result of the annealing treatments derived from X-ray diffraction and X-ray absorption analyses. Moreover, by tailoring the magnetic load, the dynamic and hydrodynamic properties of the particles were controlled, as observed by the pressure displayed against a sensor probe. Preliminary functionality experiments were performed using an eye model, seeking potential use of MPSF as reinforcement for restored detached retina. It was observed that optimal flake immobilization is obtained when the MPSF reach values of magnetic saturation >10(-4)Am(2)g(-1). Furthermore, the MPSF were demonstrated to be preliminarily biocompatible in vitro. Moreover, New Zealand rabbit in vivo models demonstrated their short-term histocompatibility and their magnetic functionality as retina pressure actuators. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Molecular Characterization of the NLRC4 Expression in Relation to Interleukin-18 Levels

PubMed Central

Zeller, Tanja; Haase, Tina; Müller, Christian; Riess, Helene; Lau, Denise; Zeller, Simon; Krause, Jasmin; Baumert, Jens; Pless, Ole; Dupuis, Josée; Wild, Philipp S.; Eleftheriadis, Medea; Waldenberger, Melanie; Zeilinger, Sonja; Ziegler, Andreas; Peters, Annette; Tiret, Laurence; Proust, Carole; Marzi, Carola; Munzel, Thomas; Strauch, Konstantin; Prokisch, Holger; Lackner, Karl J.; Herder, Christian; Thorand, Barbara; Benjamin, Emilia J.; Blankenberg, Stefan; Koenig, Wolfgang; Schnabel, Renate B.

2015-01-01

Background Interleukin-18 (IL-18) is a pleiotropic cytokine centrally involved in the cytokine cascade with complex immunomodulatory functions in innate and acquired immunity. Circulating IL-18 concentrations are associated with type 2 diabetes, cardiovascular events and diverse inflammatory and autoimmune disorders. Methods and Results To identify causal variants affecting circulating IL-18 concentrations, we applied various omics and molecular biology approaches. By GWAS, we confirmed association of IL-18 levels with a SNP in the untranslated exon 2 of the inflammasome component NLRC4 (NLR family, CARD domain containing 4) gene on chromosome 2 (rs385076, P=2.4×10−45). Subsequent molecular analyses by gene expression analysis and reporter gene assays indicated an effect of rs385076 on NLRC4 expression and differential isoform usage by modulating binding of the transcription factor PU.1. Conclusions Our study provides evidence for the functional causality of SNP rs385076 within the NLRC4 gene in relation to IL-18 activation. PMID:26362438

Post-disaster stressful life events and WTC-related posttraumatic stress, depressive symptoms, and overall functioning among responders to the World Trade Center disaster.

PubMed

Zvolensky, Michael J; Kotov, Roman; Schechter, Clyde B; Gonzalez, Adam; Vujanovic, Anka; Pietrzak, Robert H; Crane, Michael; Kaplan, Julia; Moline, Jacqueline; Southwick, Steven M; Feder, Adriana; Udasin, Iris; Reissman, Dori B; Luft, Benjamin J

2015-02-01

The current study examined contributions of post-disaster stressful life events in relation to the maintenance of WTC-related posttraumatic stress, depressive symptoms, and overall functioning among rescue, recovery, and clean-up workers who responded to the September 11, 2001 World Trade Center (WTC) terrorist attacks. Participants were 18,896 WTC responders, including 8466 police officers and 10,430 non-traditional responders (85.8% male; 86.4% Caucasian; M(age) = 39.5, SD = 8.8) participating in the WTC Health Program who completed an initial examination between July, 2002 and April, 2010 and who were reassessed, on average, 2.5 years later. Path analyses were conducted to evaluate contributions of life events to the maintenance of WTC-related posttraumatic stress, depressive symptoms, and overall functioning. These analyses were stratified by police and non-traditional responder groups and adjusted for age, sex, time from 9/11 to initial visit, WTC exposures (three WTC contextual exposures: co-worker, friend, or a relative died in the disaster; co-worker, friend, or a relative injured in the disaster; and responder was exposed to the dust cloud on 9/11), and interval from initial to first follow-up visit. In both groups, WTC-related posttraumatic stress, depressive symptoms, and overall functioning were stable over the follow-up period. WTC exposures were related to these three outcomes at the initial assessment. WTC-related posttraumatic stress, depressive symptoms, and overall functioning, at the initial assessment each predicted the occurrence of post-disaster stressful life events, as measured by Disaster Supplement of the Diagnostic Interview Schedule. Post-disaster stressful life events, in turn, were associated with subsequent mental health, indicating partial mediation of the stability of observed mental health. The present findings suggest a dynamic interplay between exposure, post-disaster stressful life events, and WTC-related posttraumatic stress, depressive symptoms, and overall functioning among WTC disaster responders. Published by Elsevier Ltd.

Age differences in the frontoparietal cognitive control network: Implications for distractibility

PubMed Central

Campbell, Karen L.; Grady, Cheryl L.; Ng, Charisa; Hasher, Lynn

2016-01-01

Current evidence suggests that older adults have reduced suppression of, and greater implicit memory for, distracting stimuli, due to age-related declines in frontal-based control mechanisms. In this study, we used fMRI to examine age differences in the neural underpinnings of attentional control and their relationship to differences in distractibility and subsequent memory for distraction. Older and younger adults were shown a rapid stream of words or nonwords superimposed on objects and performed a 1-back task on either the letters or the objects, while ignoring the other modality. Older adults were more distracted than younger adults by the overlapping words during the 1-back task, and they subsequently showed more priming for these words on an implicit memory task. A multivariate analysis of the imaging data revealed a set of regions, including the rostral PFC and inferior parietal cortex, that younger adults activated to a greater extent than older adults during the ignore-words condition, and activity in this set of regions was negatively correlated with priming for the distracting words. Functional connectivity analyses using right and left rostral PFC seeds revealed a network of putative control regions, including bilateral parietal cortex, connected to the frontal seeds at rest. Older adults showed reduced functional connectivity within this frontoparietal network, suggesting that their greater distractibility may be due to decreased activity and coherence within a cognitive control network that normally acts to reduce interference from distraction. PMID:22659108

Msx2 Prevents Stratified Squamous Epithelium Formation in the Enamel Organ.

PubMed

Nakatomi, M; Ida-Yonemochi, H; Nakatomi, C; Saito, K; Kenmotsu, S; Maas, R L; Ohshima, H

2018-06-01

Tooth enamel is manufactured by the inner enamel epithelium of the multilayered enamel organ. Msx2 loss-of-function mutation in a mouse model causes an abnormal accumulation of epithelial cells in the enamel organ, but the underlying mechanism by which Msx2 regulates amelogenesis is poorly understood. We therefore performed detailed histological and molecular analyses of Msx2 null mice. Msx2 null ameloblasts and stratum intermedium (SI) cells differentiated normally in the early stages of amelogenesis. However, during subsequent developmental stages, the outer enamel epithelium (OEE) became highly proliferative and transformed into a keratinized stratified squamous epithelium that ectopically expressed stratified squamous epithelium markers, including Heat shock protein 25, Loricrin, and Keratin 10. Moreover, expression of hair follicle-specific keratin genes such as Keratin 26 and Keratin 73 was upregulated in the enamel organ of Msx2 mutants. With the accumulation of keratin in the stellate reticulum (SR) region and subsequent odontogenic cyst formation, SI cells gradually lost the ability to differentiate, and the expression of Sox2 and Notch1 was downregulated, leading to ameloblast depolarization. As a consequence, the organization of the Msx2 mutant enamel organ became disturbed and enamel failed to form in the normal location. Instead, there was ectopic mineralization that likely occurred within the SR. In summary, we show that during amelogenesis, Msx2 executes a bipartite function, repressing the transformation of OEE into a keratinized stratified squamous epithelium while simultaneously promoting the development of a properly differentiated enamel organ competent for enamel formation.

Microdissection of black widow spider silk-producing glands.

PubMed

Jeffery, Felicia; La Mattina, Coby; Tuton-Blasingame, Tiffany; Hsia, Yang; Gnesa, Eric; Zhao, Liang; Franz, Andreas; Vierra, Craig

2011-01-11

Modern spiders spin high-performance silk fibers with a broad range of biological functions, including locomotion, prey capture and protection of developing offspring. Spiders accomplish these tasks by spinning several distinct fiber types that have diverse mechanical properties. Such specialization of fiber types has occurred through the evolution of different silk-producing glands, which function as small biofactories. These biofactories manufacture and store large quantities of silk proteins for fiber production. Through a complex series of biochemical events, these silk proteins are converted from a liquid into a solid material upon extrusion. Mechanical studies have demonstrated that spider silks are stronger than high-tensile steel. Analyses to understand the relationship between the structure and function of spider silk threads have revealed that spider silk consists largely of proteins, or fibroins, that have block repeats within their protein sequences. Common molecular signatures that contribute to the incredible tensile strength and extensibility of spider silks are being unraveled through the analyses of translated silk cDNAs. Given the extraordinary material properties of spider silks, research labs across the globe are racing to understand and mimic the spinning process to produce synthetic silk fibers for commercial, military and industrial applications. One of the main challenges to spinning artificial spider silk in the research lab involves a complete understanding of the biochemical processes that occur during extrusion of the fibers from the silk-producing glands. Here we present a method for the isolation of the seven different silk-producing glands from the cobweaving black widow spider, which includes the major and minor ampullate glands [manufactures dragline and scaffolding silk], tubuliform [synthesizes egg case silk], flagelliform [unknown function in cob-weavers], aggregate [makes glue silk], aciniform [synthesizes prey wrapping and egg case threads] and pyriform [produces attachment disc silk]. This approach is based upon anesthetizing the spider with carbon dioxide gas, subsequent separation of the cephalothorax from the abdomen, and microdissection of the abdomen to obtain the silk-producing glands. Following the separation of the different silk-producing glands, these tissues can be used to retrieve different macromolecules for distinct biochemical analyses, including quantitative real-time PCR, northern- and western blotting, mass spectrometry (MS or MS/MS) analyses to identify new silk protein sequences, search for proteins that participate in the silk assembly pathway, or use the intact tissue for cell culture or histological experiments.

Interplay of Filaggrin Loss-of-Function Variants, Allergic Sensitization, and Eczema in a Longitudinal Study Covering Infancy to 18 Years of Age

PubMed Central

Ziyab, Ali H.; Karmaus, Wilfried; Yousefi, Mitra; Ewart, Susan; Schauberger, Eric; Holloway, John W.; Zhang, Hongmei; Arshad, Syed Hasan

2012-01-01

Background Immune specific genes as well as genes regulating the formation of skin barrier are major determinants for eczema manifestation. There is a debate as to whether allergic sensitization and filaggrin gene (FLG) variants lead to eczema or FLG variants and eczema increase the risk of allergic sensitization. To investigate the time-order between eczema and allergic sensitization with respect to FLG variants, data from a large prospective study covering infancy to late adolescence were analyzed. Methodology/Principal Findings Repeated measurements of eczema and allergic sensitization (documented by skin prick tests) at ages 1, 2, 4, 10, and 18 years were ascertained in the Isle of Wight birth cohort (n = 1,456). Three transition periods were analyzed: age 1-or-2 to 4, 4 to 10, and 10 to 18 years. FLG variants were genotyped in 1,150 participants. Over the three transition periods, in temporal sequence analyses of initially eczema-free participants, the combined effect of FLG variants and allergic sensitization showed a 2.92-fold (95% CI: 1.47–5.77) increased risk ratio (RR) of eczema in subsequent examinations. This overall risk was more pronounced at a younger age (transition period 1-or-2 to 4, RR = 6.47, 95% CI: 1.96–21.33). In contrast, FLG variants in combination with eczema showed a weaker, but significant, risk ratio for subsequent allergic sensitization only up to 10 years of age. Conclusions/Significance Taking the time order into account, this prospective study demonstrates for the first time, that a combination of FLG variants and allergic sensitization increased the risk of eczema in subsequent years. Also FLG variants interacted with eczema and increased the risk of subsequent allergic sensitization, which, was limited to the younger age. Hence, early restoration of defective skin barrier could prevent allergic sensitization and subsequently reduce the risk of eczema development. PMID:22403702

Substrate-Mediated Laser Ablation under Ambient Conditions for Spatially-Resolved Tissue Proteomics

PubMed Central

Fatou, Benoit; Wisztorski, Maxence; Focsa, Cristian; Salzet, Michel; Ziskind, Michael; Fournier, Isabelle

2015-01-01

Numerous applications of ambient Mass Spectrometry (MS) have been demonstrated over the past decade. They promoted the emergence of various micro-sampling techniques such as Laser Ablation/Droplet Capture (LADC). LADC consists in the ablation of analytes from a surface and their subsequent capture in a solvent droplet which can then be analyzed by MS. LADC is thus generally performed in the UV or IR range, using a wavelength at which analytes or the matrix absorb. In this work, we explore the potential of visible range LADC (532 nm) as a micro-sampling technology for large-scale proteomics analyses. We demonstrate that biomolecule analyses using 532 nm LADC are possible, despite the low absorbance of biomolecules at this wavelength. This is due to the preponderance of an indirect substrate-mediated ablation mechanism at low laser energy which contrasts with the conventional direct ablation driven by sample absorption. Using our custom LADC system and taking advantage of this substrate-mediated ablation mechanism, we were able to perform large-scale proteomic analyses of micro-sampled tissue sections and demonstrated the possible identification of proteins with relevant biological functions. Consequently, the 532 nm LADC technique offers a new tool for biological and clinical applications. PMID:26674367

The utility of estimating population-level trajectories of terminal wellbeing decline within a growth mixture modelling framework.

PubMed

Burns, R A; Byles, J; Magliano, D J; Mitchell, P; Anstey, K J

2015-03-01

Mortality-related decline has been identified across multiple domains of human functioning, including mental health and wellbeing. The current study utilised a growth mixture modelling framework to establish whether a single population-level trajectory best describes mortality-related changes in both wellbeing and mental health, or whether subpopulations report quite different mortality-related changes. Participants were older-aged (M = 69.59 years; SD = 8.08 years) deceased females (N = 1,862) from the dynamic analyses to optimise ageing (DYNOPTA) project. Growth mixture models analysed participants' responses on measures of mental health and wellbeing for up to 16 years from death. Multi-level models confirmed overall terminal decline and terminal drop in both mental health and wellbeing. However, modelling data from the same participants within a latent class growth mixture framework indicated that most participants reported stability in mental health (90.3 %) and wellbeing (89.0 %) in the years preceding death. Whilst confirming other population-level analyses which support terminal decline and drop hypotheses in both mental health and wellbeing, we subsequently identified that most of this effect is driven by a small, but significant minority of the population. Instead, most individuals report stable levels of mental health and wellbeing in the years preceding death.

Baseline Functioning and Stress Reactivity in Maltreating Parents and At-Risk Adults

PubMed Central

Reijman, Sophie; Bakermans-Kranenburg, Marian J.; Hiraoka, Regina; Crouch, Julie L.; Milner, Joel S.; van IJzendoorn, Marinus H.

2016-01-01

We reviewed and meta-analyzed 10 studies (N = 492) that examined the association between (risk for) child maltreatment perpetration and basal autonomic activity, and 10 studies (N = 471) that examined the association between (risk for) child maltreatment and autonomic stress reactivity. We hypothesized that maltreating parents/at-risk adults would show higher basal levels of heart rate (HR) and skin conductance (SC) and lower levels of HR variability (HRV) and would show greater HR and SC stress reactivity, but blunted HRV reactivity. A narrative review showed that evidence from significance testing within and across studies was mixed. The first set of meta-analyses revealed that (risk for) child maltreatment was associated with higher HR baseline activity (g = 0.24), a possible indication of allostatic load. The second set of meta-analyses yielded no differences in autonomic stress reactivity between maltreating/at-risk participants and nonmaltreating/low-risk comparison groups. Cumulative meta-analyses showed that positive effects for sympathetic stress reactivity as a risk factor for child maltreatment were found in a few early studies, whereas each subsequently aggregated study reduced the combined effect size to a null effect, an indication of the winner’s curse. Most studies were underpowered. Future directions for research are suggested. PMID:27462035

Muscle precursor cells in the developing limbs of two isopods (Crustacea, Peracarida): an immunohistochemical study using a novel monoclonal antibody against myosin heavy chain

PubMed Central

Kreissl, S.; Uber, A.

2008-01-01

In the hot debate on arthropod relationships, Crustaceans and the morphology of their appendages play a pivotal role. To gain new insights into how arthropod appendages evolved, developmental biologists recently have begun to examine the expression and function of Drosophila appendage genes in Crustaceans. However, cellular aspects of Crustacean limb development such as myogenesis are poorly understood in Crustaceans so that the interpretative context in which to analyse gene functions is still fragmentary. The goal of the present project was to analyse muscle development in Crustacean appendages, and to that end, monoclonal antibodies against arthropod muscle proteins were generated. One of these antibodies recognises certain isoforms of myosin heavy chain and strongly binds to muscle precursor cells in malacostracan Crustacea. We used this antibody to study myogenesis in two isopods, Porcellio scaber and Idotea balthica (Crustacea, Malacostraca, Peracarida), by immunohistochemistry. In these animals, muscles in the limbs originate from single muscle precursor cells, which subsequently grow to form multinucleated muscle precursors. The pattern of primordial muscles in the thoracic limbs was mapped, and results compared to muscle development in other Crustaceans and in insects. Electronic supplementary material The online version of this article (doi:10.1007/s00427-008-0216-1) contains supplementary material, which is available to authorized users. PMID:18443823

Discovering genetic variants in Crohn's disease by exploring genomic regions enriched of weak association signals.

PubMed

D'Addabbo, Annarita; Palmieri, Orazio; Maglietta, Rosalia; Latiano, Anna; Mukherjee, Sayan; Annese, Vito; Ancona, Nicola

2011-08-01

A meta-analysis has re-analysed previous genome-wide association scanning definitively confirming eleven genes and further identifying 21 new loci. However, the identified genes/loci still explain only the minority of genetic predisposition of Crohn's disease. To identify genes weakly involved in disease predisposition by analysing chromosomal regions enriched of single nucleotide polymorphisms with modest statistical association. We utilized the WTCCC data set evaluating 1748 CD and 2938 controls. The identification of candidate genes/loci was performed by a two-step procedure: first of all chromosomal regions enriched of weak association signals were localized; subsequently, weak signals clustered in gene regions were identified. The statistical significance was assessed by non parametric permutation tests. The cytoband enrichment analysis highlighted 44 regions (P≤0.05) enriched with single nucleotide polymorphisms significantly associated with the trait including 23 out of 31 previously confirmed and replicated genes. Importantly, we highlight further 20 novel chromosomal regions carrying approximately one hundred genes/loci with modest association. Amongst these we find compelling functional candidate genes such as MAPT, GRB2 and CREM, LCT, and IL12RB2. Our study suggests a different statistical perspective to discover genes weakly associated with a given trait, although further confirmatory functional studies are needed. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. All rights reserved.

Method for reducing measurement errors of a Langmuir probe with a protective RF shield

NASA Astrophysics Data System (ADS)

Riaby, V.; Masherov, P.; Savinov, V.; Yakunin, V.

2018-04-01

Probe measurements were conducted in the middle cross-section of an inductive, low-pressure xenon plasma using a straight cylindrical Langmuir probe with a bare metal shield that protected the probe from radio frequency interference. As a result, reliable radial distributions of the plasma parameters were obtained. Subsequent analyses of these measurements revealed that the electron energy distribution function (EEDF) deviated substantially from the Maxwellian functions and that this deviation depended on the length of the probe shield. To evaluate the shield's influence on the measurement results, in addition to the probe (which was moved radially as its shield length varied in the range of lsh1 = lmax-0), an additional L-shaped probe was inserted at a different location. This probe was moved differently from the first probe and provided confirmational measurements in the common special position where lsh1 = 0 and lsh2 ≠ 0. In this position, the second shield decreased all the plasma parameters. A comparison of the probe datasets identified the principles of the relationships between measurement errors and EEDF distortions caused by the bare probe shields. This dependence was used to correct the measurements performed using the first probe by eliminating the influence of its shield. Physical analyses based on earlier studies showed that these peculiarities are caused by a short-circuited double-probe effect that occurs in bare metal probe protective shields.

The cingulo-opercular network provides word-recognition benefit.

PubMed

Vaden, Kenneth I; Kuchinsky, Stefanie E; Cute, Stephanie L; Ahlstrom, Jayne B; Dubno, Judy R; Eckert, Mark A

2013-11-27

Recognizing speech in difficult listening conditions requires considerable focus of attention that is often demonstrated by elevated activity in putative attention systems, including the cingulo-opercular network. We tested the prediction that elevated cingulo-opercular activity provides word-recognition benefit on a subsequent trial. Eighteen healthy, normal-hearing adults (10 females; aged 20-38 years) performed word recognition (120 trials) in multi-talker babble at +3 and +10 dB signal-to-noise ratios during a sparse sampling functional magnetic resonance imaging (fMRI) experiment. Blood oxygen level-dependent (BOLD) contrast was elevated in the anterior cingulate cortex, anterior insula, and frontal operculum in response to poorer speech intelligibility and response errors. These brain regions exhibited significantly greater correlated activity during word recognition compared with rest, supporting the premise that word-recognition demands increased the coherence of cingulo-opercular network activity. Consistent with an adaptive control network explanation, general linear mixed model analyses demonstrated that increased magnitude and extent of cingulo-opercular network activity was significantly associated with correct word recognition on subsequent trials. These results indicate that elevated cingulo-opercular network activity is not simply a reflection of poor performance or error but also supports word recognition in difficult listening conditions.

Dynamic behaviour of a rotating cracked beam

NASA Astrophysics Data System (ADS)

Yashar, Ahmed; Ghandchi-Tehrani, Maryam; Ferguson, Neil

2016-09-01

This paper presents a new approach to investigate and analyse the vibrational behaviour of cracked rotating cantilever beams, which can for example represent helicopter or wind turbine blades. The analytical Hamiltonian method is used in modelling the rotating beam and two numerical methods, the Rayleigh-Ritz and FEM, are used to study the natural frequencies and the mode shapes of the intact rotating beams. Subsequently, a crack is introduced into the FE model and simulations are performed to identify the modal characteristics for an open cracked rotating beam. The effect of various parameters such as non-dimensional rotating speed, hub ratio and slenderness ratio are investigated for both the intact and the cracked rotating beam, and in both directions of chordwise and flapwise motion. The veering phenomena in the natural frequencies as a function of the rotational speed and the buckling speed are considered with respect to the slenderness ratio. In addition, the mode shapes obtained for the flapwise vibration are compared using the modal assurance criterion (MAC). Finally, a new three dimensional design chart is produced, showing the effect of crack location and depth on the natural frequencies of the rotating beam. This chart will be subsequently important in identifying crack defects in rotating blades.

Preparation of silica-coated poly(styrene-co-4-vinylpyridine) particles and hollow particles.

PubMed

Zou, Hua; Wu, Shishan; Shen, Jian

2008-09-16

This paper presents a novel method for preparation of polymer-silica colloidal nanocomposites based on emulsion polymerization and subsequent sol-gel nanocoating process. The polystyrene latex particles bearing basic groups on their surfaces were successfully synthesized through emulsion polymerization using 4-vinylpyridine (4VP) as a functional comonomer and polyvinylpyrrolidone (PVP) as a surfactant. A series of poly(styrene-co-4-vinylpyridine)/SiO2 nanocomposite particles with smooth or rough core-shell morphology were obtained through the coating process. The poly(styrene-co-4-vinylpyridine) particles could be dissolved subsequently or simultaneously during the sol-gel coating process to form hollow particles. The effects of the amount of 4VP, PVP, NH(4)OH, and tetraethoxysilane (TEOS) on both the nanocomposite particles and hollow particles were investigated. Transmission electron microscopy showed that the morphology of the nanocomposite particles and hollow particles was strongly influenced by the initial feed of the comonomer 4VP and the coupling agent PVP. The conditions to obtain all hollow particles were also studied. Thermogravimetric analysis and energy dispersive X-ray spectroscopy analyses indicated that the interiors of hollow particles were not really "hollow".

The timing of sequences of saccades in visual search.

PubMed Central

Van Loon, E M; Hooge, I Th C; Van den Berg, A V

2002-01-01

According to the LATER model (linear approach to thresholds with ergodic rate), the latency of a single saccade in response to target appearance can be understood as a decision process, which is subject to (i) variations in the rate of (visual) information processing; and (ii) the threshold for the decision. We tested whether the LATER model can also be applied to the sequences of saccades in a multiple fixation search, during which latencies of second and subsequent saccades are typically shorter than that of the initial saccade. We found that the distributions of the reciprocal latencies for later saccades, unlike those of the first saccade, are highly asymmetrical, much like a gamma distribution. This suggests that the normal distribution of the rate r, which the LATER model assumes, is not appropriate to describe the rate distributions of subsequent saccades in a scanning sequence. By contrast, the gamma distribution is also appropriate to describe the distribution of reciprocal latencies for the first saccade. The change of the gamma distribution parameters as a function of the ordinal number of the saccade suggests a lowering of the threshold for second and later saccades, as well as a reduction in the number of target elements analysed. PMID:12184827

Shifting Visual Perspective During Retrieval Shapes Autobiographical Memories

PubMed Central

St Jacques, Peggy L.; Szpunar, Karl K.; Schacter, Daniel L.

2016-01-01

The dynamic and flexible nature of memories is evident in our ability to adopt multiple visual perspectives. Although autobiographical memories are typically encoded from the visual perspective of our own eyes they can be retrieved from the perspective of an observer looking at our self. Here, we examined the neural mechanisms of shifting visual perspective during long-term memory retrieval and its influence on online and subsequent memories using functional magnetic resonance imaging (fMRI). Participants generated specific autobiographical memories from the last five years and rated their visual perspective. In a separate fMRI session, they were asked to retrieve the memories across three repetitions while maintaining the same visual perspective as their initial rating or by shifting to an alternative perspective. Visual perspective shifting during autobiographical memory retrieval was supported by a linear decrease in neural recruitment across repetitions in the posterior parietal cortices. Additional analyses revealed that the precuneus, in particular, contributed to both online and subsequent changes in the phenomenology of memories. Our findings show that flexibly shifting egocentric perspective during autobiographical memory retrieval is supported by the precuneus, and suggest that this manipulation of mental imagery during retrieval has consequences for how memories are retrieved and later remembered. PMID:27989780

Novel GABRG2 mutations cause familial febrile seizures

PubMed Central

Boillot, Morgane; Morin-Brureau, Mélanie; Picard, Fabienne; Weckhuysen, Sarah; Lambrecq, Virginie; Minetti, Carlo; Striano, Pasquale; Zara, Federico; Iacomino, Michele; Ishida, Saeko; An-Gourfinkel, Isabelle; Daniau, Mailys; Hardies, Katia; Baulac, Michel; Dulac, Olivier; Leguern, Eric; Nabbout, Rima

2015-01-01

Objective: To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. Methods: The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Results: Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort. Conclusions: We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism. PMID:27066572

A plasma modified cellulose-chitosan porous membrane allows efficient DNA binding and provides antibacterial properties: A step towards developing a new DNA collecting card.

PubMed

Chumwangwapee, Sasiwimon; Chingsungnoen, Artit; Siri, Sineenat

2016-11-01

In forensic DNA analyses, biological specimens are collected and stored for subsequent recovery and analysis of DNA. A cost-effective and efficient DNA recovery approach is therefore a need. This study aims to produce a plasma modified cellulose-chitosan membrane (pCE-CS) that efficiently binds and retains DNA as a potential DNA collecting card. The pCE-CS membrane was produced by a phase separation of ionic liquid dissolving CE and CS in water with subsequent surface-modification by a two-step exposure of argon plasma and nitrogen gas. Through plasma modification, the pCE-CS membrane demonstrated better DNA retention after a washing process and higher rate of DNA recovery as compared with the original CE-CS membrane and the commercial FTA card. In addition, the pCE-CS membrane exhibited anti-bacterial properties against both Escherichia coli and Staphylococcus aureus. The results of this work suggest a potential function of the pCE-CS membrane as a DNA collecting card with a high recovery rate of captured DNA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Intrusive Memories of Distressing Information: An fMRI Study

PubMed Central

Battaglini, Eva; Liddell, Belinda; Das, Pritha; Malhi, Gin; Felmingham, Kim

2016-01-01

Although intrusive memories are characteristic of many psychological disorders, the neurobiological underpinning of these involuntary recollections are largely unknown. In this study we used functional magentic resonance imaging (fMRI) to identify the neural networks associated with encoding of negative stimuli that are subsequently experienced as intrusive memories. Healthy partipants (N = 42) viewed negative and neutral images during a visual/verbal processing task in an fMRI context. Two days later they were assessed on the Impact of Event Scale for occurrence of intrusive memories of the encoded images. A sub-group of participants who reported significant intrusions (n = 13) demonstrated stronger activation in the amygdala, bilateral ACC and parahippocampal gyrus during verbal encoding relative to a group who reported no intrusions (n = 13). Within-group analyses also revealed that the high intrusion group showed greater activity in the dorsomedial (dmPFC) and dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus and occipital regions during negative verbal processing compared to neutral verbal processing. These results do not accord with models of intrusions that emphasise visual processing of information at encoding but are consistent with models that highlight the role of inhibitory and suppression processes in the formation of subsequent intrusive memories. PMID:27685784

Novel GABRG2 mutations cause familial febrile seizures.

PubMed

Boillot, Morgane; Morin-Brureau, Mélanie; Picard, Fabienne; Weckhuysen, Sarah; Lambrecq, Virginie; Minetti, Carlo; Striano, Pasquale; Zara, Federico; Iacomino, Michele; Ishida, Saeko; An-Gourfinkel, Isabelle; Daniau, Mailys; Hardies, Katia; Baulac, Michel; Dulac, Olivier; Leguern, Eric; Nabbout, Rima; Baulac, Stéphanie

2015-12-01

To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy. The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening. Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort. We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism.

The relation between patient discomfort and uncompensated forces of a patient support device for breast and regional lymph node radiotherapy.

PubMed

Boute, Bert; Veldeman, Liv; Speleers, Bruno; Van Greveling, Annick; Van Hoof, Tom; Van de Velde, Joris; Vercauteren, Tom; De Neve, Wilfried; Detand, Jan

2018-10-01

Although many authors stated that a user-centred design approach in medical device development has added values, the most common research approach within healthcare is evidence-based medicine, which tend to focus on functional data rather than patient wellbeing and comfort. End user comfort is well addressed in literature for commercial products such as seats and hand tools but no data was found for medical devices. A commercial patient support device for breast radiotherapy was analysed and a relation was found between discomfort and uncompensated internal body forces. Derived from CT-images, simplified patient free-body diagrams were analysed and pain and comfort evaluated. Subsequently, a new patient position was established and prototypes were developed. Patient comfort- and prototype optimization was done through iterative prototyping. With this approach, we were able to compensate all internal body forces and establish a force neutral patient free-body diagram. This resulted in comfortable patient positioning and favourable medical results. Copyright © 2018 Elsevier Ltd. All rights reserved.

Perceived social isolation makes me sad: 5-year cross-lagged analyses of loneliness and depressive symptomatology in the Chicago Health, Aging, and Social Relations Study.

PubMed

Cacioppo, John T; Hawkley, Louise C; Thisted, Ronald A

2010-06-01

We present evidence from a 5-year longitudinal study for the prospective associations between loneliness and depressive symptoms in a population-based, ethnically diverse sample of 229 men and women who were 50-68 years old at study onset. Cross-lagged panel models were used in which the criterion variables were loneliness and depressive symptoms, considered simultaneously. We used variations on this model to evaluate the possible effects of gender, ethnicity, education, physical functioning, medications, social network size, neuroticism, stressful life events, perceived stress, and social support on the observed associations between loneliness and depressive symptoms. Cross-lagged analyses indicated that loneliness predicted subsequent changes in depressive symptomatology, but not vice versa, and that this temporal association was not attributable to demographic variables, objective social isolation, dispositional negativity, stress, or social support. The importance of distinguishing between loneliness and depressive symptoms and the implications for loneliness and depressive symptomatology in older adults are discussed. (c) 2010 APA, all rights reserved

Conditioned taste aversion dependent regulation of amygdala gene expression.

PubMed

Panguluri, Siva K; Kuwabara, Nobuyuki; Kang, Yi; Cooper, Nigel; Lundy, Robert F

2012-02-28

The present experiments investigated gene expression in the amygdala following contingent taste/LiCl treatment that supports development of conditioned taste aversion (CTA). The use of whole genome chips and stringent data set filtering led to the identification of 168 genes regulated by CTA compared to non-contingent LiCl treatment that does not support CTA learning. Seventy-six of these genes were eligible for network analysis. Such analysis identified "behavior" as the top biological function, which was represented by 15 of the 76 genes. These genes included several neuropeptides, G protein-coupled receptors, ion channels, kinases, and phosphatases. Subsequent qRT-PCR analyses confirmed changes in mRNA expression for 5 of 7 selected genes. We were able to demonstrate directionally consistent changes in protein level for 3 of these genes; insulin 1, oxytocin, and major histocompatibility complex class I-C. Behavioral analyses demonstrated that blockade of central insulin receptors produced a weaker CTA that was less resistant to extinction. Together, these results support the notion that we have identified downstream genes in the amygdala that contribute to CTA learning. Copyright © 2011 Elsevier Inc. All rights reserved.

Physiological and Proteomics Analyses Reveal the Mechanism of Eichhornia crassipes Tolerance to High-Concentration Cadmium Stress Compared with Pistia stratiotes

PubMed Central

Yang, Yunqiang; Yang, Shihai; Sun, Xudong; Yang, Yongping

2015-01-01

Cadmium (Cd) pollution is an environmental problem worldwide. Phytoremediation is a convenient method of removing Cd from both soil and water, but its efficiency is still low, especially in aquatic environments. Scientists have been trying to improve the ability of plants to absorb and accumulate Cd based on interactions between plants and Cd, especially the mechanism by which plants resist Cd. Eichhornia crassipes and Pistia stratiotes are aquatic plants commonly used in the phytoremediation of heavy metals. In the present study, we conducted physiological and biochemical analyses to compare the resistance of these two species to Cd stress at 100 mg/L. E. crassipes showed stronger resistance and was therefore used for subsequent comparative proteomics to explore the potential mechanism of E. crassipes tolerance to Cd stress at the protein level. The expression patterns of proteins in different functional categories revealed that the physiological activities and metabolic processes of E. crassipes were affected by exposure to Cd stress. However, when some proteins related to these processes were negatively inhibited, some analogous proteins were induced to compensate for the corresponding functions. As a result, E. crassipes could maintain more stable physiological parameters than P. stratiotes. Many stress-resistance substances and proteins, such as proline and heat shock proteins (HSPs) and post translational modifications, were found to be involved in the protection and repair of functional proteins. In addition, antioxidant enzymes played important roles in ROS detoxification. These findings will facilitate further understanding of the potential mechanism of plant response to Cd stress at the protein level. PMID:25886466

Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer: An individual patient data meta‐analysis of 22 RCTs

PubMed Central

Kalter, J.; Verdonck‐de Leeuw, I.M.; Sweegers, M.G.; Aaronson, N.K.; Jacobsen, P.B.; Newton, R.U.; Courneya, K.S.; Aitken, J.F.; Armes, J.; Arving, C.; Boersma, L.J.; Braamse, A.M.J.; Brandberg, Y.; Chambers, S.K.; Dekker, J.; Ell, K.; Ferguson, R.J.; Gielissen, M.F.M.; Glimelius, B.; Goedendorp, M.M.; Graves, K.D.; Heiney, S.P.; Horne, R.; Hunter, M.S.; Johansson, B.; Kimman, M.L.; Knoop, H.; Meneses, K.; Northouse, L.L.; Oldenburg, H.S.; Prins, J.B.; Savard, J.; van Beurden, M.; van den Berg, S.W.; Brug, J.

2018-01-01

Abstract Objective This individual patient data (IPD) meta‐analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention‐related characteristics. Methods Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed‐effect model analyses were used to study intervention effects on the post‐intervention values of QoL, EF, and SF (z‐scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention‐related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (β = 0.14,95%CI = 0.06;0.21), EF (β = 0.13,95%CI = 0.05;0.20), and SF (β = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention‐related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients. PMID:29361206

Suppressing Emotions Impairs Subsequent Stroop Performance and Reduces Prefrontal Brain Activation

PubMed Central

Luechinger, Roger; Boesiger, Peter; Rasch, Björn

2013-01-01

Abundant behavioral evidence suggests that the ability to self-control is limited, and that any exertion of self-control will increase the likelihood of subsequent self-control failures. Here we investigated the neural correlates underlying the aftereffects of self-control on future control processes using functional magnetic resonance imaging (fMRI). An initial act of self-control (suppressing emotions) impaired subsequent performance in a second task requiring control (Stroop task). On the neural level, increased activity during emotion suppression was followed by a relative decrease in activity during the Stroop task in a cluster in the right lateral prefrontal cortex (PFC) including the dorsolateral prefrontal cortex (DLPFC), an area engaged in the effortful implementation of control. There was no reliable evidence for reduced activity in the medial frontal cortex (MFC) including the anterior cingulate cortex (ACC), which is involved in conflict detection processes and has previously also been implicated in self-control. Follow-up analyses showed that the detected cluster in the right lateral PFC and an area in the MFC were involved in both the emotion suppression task and the Stroop task, but only the cluster in the right lateral PFC showed reduced activation after emotion suppression during the Stroop task. Reduced activity in lateral prefrontal areas relevant for the implementation of control may be a critical consequence of prior self-control exertion if the respective areas are involved in both self-control tasks. PMID:23565239

Poor replication validity of biomedical association studies reported by newspapers

PubMed Central

Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

Objective To investigate the replication validity of biomedical association studies covered by newspapers. Methods We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Results Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Conclusion Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed. PMID:28222122

Poor replication validity of biomedical association studies reported by newspapers.

PubMed

Dumas-Mallet, Estelle; Smith, Andy; Boraud, Thomas; Gonon, François

2017-01-01

To investigate the replication validity of biomedical association studies covered by newspapers. We used a database of 4723 primary studies included in 306 meta-analysis articles. These studies associated a risk factor with a disease in three biomedical domains, psychiatry, neurology and four somatic diseases. They were classified into a lifestyle category (e.g. smoking) and a non-lifestyle category (e.g. genetic risk). Using the database Dow Jones Factiva, we investigated the newspaper coverage of each study. Their replication validity was assessed using a comparison with their corresponding meta-analyses. Among the 5029 articles of our database, 156 primary studies (of which 63 were lifestyle studies) and 5 meta-analysis articles were reported in 1561 newspaper articles. The percentage of covered studies and the number of newspaper articles per study strongly increased with the impact factor of the journal that published each scientific study. Newspapers almost equally covered initial (5/39 12.8%) and subsequent (58/600 9.7%) lifestyle studies. In contrast, initial non-lifestyle studies were covered more often (48/366 13.1%) than subsequent ones (45/3718 1.2%). Newspapers never covered initial studies reporting null findings and rarely reported subsequent null observations. Only 48.7% of the 156 studies reported by newspapers were confirmed by the corresponding meta-analyses. Initial non-lifestyle studies were less often confirmed (16/48) than subsequent ones (29/45) and than lifestyle studies (31/63). Psychiatric studies covered by newspapers were less often confirmed (10/38) than the neurological (26/41) or somatic (40/77) ones. This is correlated to an even larger coverage of initial studies in psychiatry. Whereas 234 newspaper articles covered the 35 initial studies that were later disconfirmed, only four press articles covered a subsequent null finding and mentioned the refutation of an initial claim. Journalists preferentially cover initial findings although they are often contradicted by meta-analyses and rarely inform the public when they are disconfirmed.

Attachment to Life: Psychometric Analyses of the Valuation of Life Scale and Differences Among Older Adults

PubMed Central

Gitlin, Laura N.; Parisi, Jeanine; Huang, Jin; Winter, Laraine; Roth, David L.

2016-01-01

Purpose of study: Examine psychometric properties of Lawton’s Valuation of Life (VOL) scale, a measure of an older adults’ assessment of the perceived value of their lives; and whether ratings differ by race (White, Black/African American) and sex. Design and Methods: The 13-item VOL scale was administered at baseline in 2 separate randomized trials (Advancing Better Living for Elders, ABLE; Get Busy Get Better, GBGB) for a total of 527 older adults. Principal component analyses were applied to a subset of ABLE data (subsample 1) and confirmatory factor analyses were conducted on remaining data (subsample 2 and GBGB). Once the factor structure was identified and confirmed, 2 subscales were created, corresponding to optimism and engagement. Convergent validity of total and subscale scores were examined using measures of depressive symptoms, social support, control-oriented strategies, mastery, and behavioral activation. For discriminant validity, indices of health status, physical function, financial strain, cognitive status, and number of falls were examined. Results: Trial samples (ABLE vs. GBGB) differed by age, race, marital status, education, and employment. Principal component analysis on ABLE subsample 1 (n = 156) yielded two factors subsequently confirmed in confirmatory factor analyses on ABLE subsample 2 (n = 163) and GBGB sample (N = 208) separately. Adequate fit was found for the 2-factor model. Correlational analyses supported strong convergent and discriminant validity. Some statistically significant race and sex differences in subscale scores were found. Implications: VOL measures subjective appraisals of perceived value of life. Consisting of two interrelated subscales, it offers an efficient approach to ascertain personal attributions. PMID:26874189

A Survival Analysis of Adolescent Friendships: The Downside of Dissimilarity

PubMed Central

Hartl, Amy C.; Laursen, Brett; Cillessen, Antonius H. N.

2015-01-01

The present study examined whether adolescent friendships dissolve because of characteristics of friends, differences between friends, or both. Participants included 410 adolescents (201 boys, 209 girls) who reported a total of 573 reciprocated friendships that originated in the 7th grade (M age = 13.20 years). Discrete-time survival analyses were conducted in which peer nominations and teacher ratings collected in Grade 7 predicted the occurrence and timing of friendship dissolution across grades 8 to 12. Grade 7 individual characteristics were unrelated to friendship stability, but Grade 7 differences in sex, peer acceptance, physical aggression, and school competence predicted subsequent friendship dissolution. The findings suggest that compatibility is a function of similarity between friends rather than the presence or absence of a particular trait. PMID:26187246

Pirfenidone safety and adverse event management in idiopathic pulmonary fibrosis.

PubMed

Lancaster, Lisa H; de Andrade, Joao A; Zibrak, Joseph D; Padilla, Maria L; Albera, Carlo; Nathan, Steven D; Wijsenbeek, Marlies S; Stauffer, John L; Kirchgaessler, Klaus-Uwe; Costabel, Ulrich

2017-12-31

Pirfenidone is one of two approved therapies for the treatment of idiopathic pulmonary fibrosis (IPF). Randomised controlled clinical trials and subsequent post hoc analyses have demonstrated that pirfenidone reduces lung function decline, decreases mortality and improves progression-free survival. Long-term extension trials, registries and real-world studies have also shown similar treatment effects with pirfenidone. However, for patients with IPF to obtain the maximum benefits of pirfenidone treatment, the potential adverse events (AEs) associated with pirfenidone need to be managed. This review highlights the well-known and established safety profile of pirfenidone based on randomised controlled clinical trials and real-world data. Key strategies for preventing and managing the most common pirfenidone-related AEs are described, with the goal of maximising adherence to pirfenidone with minimal AEs. Copyright ©ERS 2017.

Finding Semirigid Domains in Biomolecules by Clustering Pair-Distance Variations

PubMed Central

Schreiner, Wolfgang

2014-01-01

Dynamic variations in the distances between pairs of atoms are used for clustering subdomains of biomolecules. We draw on a well-known target function for clustering and first show mathematically that the assignment of atoms to clusters has to be crisp, not fuzzy, as hitherto assumed. This reduces the computational load of clustering drastically, and we demonstrate results for several biomolecules relevant in immunoinformatics. Results are evaluated regarding the number of clusters, cluster size, cluster stability, and the evolution of clusters over time. Crisp clustering lends itself as an efficient tool to locate semirigid domains in the simulation of biomolecules. Such domains seem crucial for an optimum performance of subsequent statistical analyses, aiming at detecting minute motional patterns related to antigen recognition and signal transduction. PMID:24959586

The Effects of a School-Based Functional Analysis on Subsequent Classroom Behavior

ERIC Educational Resources Information Center

Davis, Tonya N.; Durand, Shannon; Fuentes, Lisa; Dacus, Sharon; Blenden, Kara

2014-01-01

In this study we analyzed the effects of conducting a school-based functional analysis on subsequent classroom behavior. Each participant was observed in the classroom during activities that were reported by teachers to result in high levels of challenging behavior. Participants were observed during (a) baseline, prior to the administration of a…

The forest health monitoring national technical reports: examples of analyses and results from 2001-2004

Treesearch

Mark J. Ambrose; Barbara L. Conkling; Kurt H. Riitters; John W. Coulston

2008-01-01

This brochure presents examples of analyses included in the first four Forest Health Monitoring (FHM) national technical reports. Its purpose is to introduce the reader to the kinds of information available in these and subsequent FHM national technical reports. Indicators presented here include drought, air pollution, forest fragmentation, and tree mortality. These...

Interior Volatile Reservoirs in Mercury

NASA Astrophysics Data System (ADS)

Anzures, B. A.; Parman, S. W.; Milliken, R. E.; Head, J. W.

2018-05-01

More measurements of 1) surface volatiles, and 2) pyroclastic deposits paired with experimental volatile analyses in silicate minerals can constrain conditions of melting and subsequent eruption on Mercury.

Unhealthy lifestyle may increase later depression via inflammation in older women but not men.

PubMed

Hiles, Sarah A; Baker, Amanda L; de Malmanche, Theo; McEvoy, Mark; Boyle, Michael; Attia, John

2015-04-01

Depression and inflammatory markers have a reliable cross-sectional association although less is known about the prospective relationship. The current study investigated whether pro-inflammatory markers are prospectively associated with depression, and whether indicators of unhealthy lifestyle, physical health and psychosocial functioning may drive this association. Participants were drawn from the Hunter Community Study, a community-dwelling cohort of individuals aged 55-85 years (N = 1410). Participants completed baseline physiological assessment, health-related questionnaires, and blood sampling for the analysis of inflammatory markers, C-reactive protein (CRP) and interleukin (IL)-6. Participants completed the same depressive symptom questionnaire again after 3.5-5.5 years. Depression outcomes at follow-up were analysed dichotomously using established scale cut-off scores and continuously as a "residual score", representing the variation in follow-up depressive symptoms not explained by baseline symptoms and age. Analyses were conducted on males and females separately. At baseline, indicators of unhealthy lifestyle, physical health and psychosocial functioning were associated with depressive symptoms and inflammatory markers. For males, there were no relationships between inflammatory markers and follow-up depression outcomes. In females, IL-6 was significantly associated with depression outcomes in univariate, but not multivariate analyses. However, IL-6 significantly mediated the association between the predictors of waist-to-hip ratio, smoking and psychological coping at baseline, and follow-up depression outcomes. The results support the inflammatory hypothesis of depression, although females may be more vulnerable to effects. The findings raise the possibility that unhealthy lifestyle and psychosocial stress may drive inflammation and subsequent depressive symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Retrotransposed genes such as Frat3 in the mouse Chromosome 7C Prader-Willi syndrome region acquire the imprinted status of their insertion site.

PubMed

Chai, J H; Locke, D P; Ohta, T; Greally, J M; Nicholls, R D

2001-11-01

Prader-Willi syndrome (PWS) results from loss of function of a 1.0- to 1.5-Mb domain of imprinted, paternally expressed genes in human Chromosome (Chr) 15q11-q13. The loss of imprinted gene expression in the homologous region in mouse Chr 7C leads to a similar neonatal PWS phenotype. Several protein-coding genes in the human PWS region are intronless, possibly arising by retrotransposition. Here we present evidence for continued acquisition of genes by the mouse PWS region during evolution. Bioinformatic analyses identified a BAC containing four genes, Mkrn3, Magel2, Ndn, Frat3, and the Atp5l-ps1 pseudogene, the latter two genes derived from recent L1-mediated retrotransposition. Analyses of eight overlapping BACs indicate that these genes are clustered within 120 kb in two inbred strains, in the order tel-Atp5l-ps1-Frat3-Mkrn3-Magel2-Ndn-cen. Imprinting analyses show that Frat3 is differentially methylated and expressed solely from the paternal allele in a transgenic mouse model of Angelman syndrome, with no expression from the maternal allele in a mouse model of PWS. Loss of Frat3 expression may, therefore, contribute to the phenotype of mouse models of PWS. The identification of five intronless genes in a small genomic interval suggests that this region is prone to retroposition in germ cells or their zygotic and embryonic cell precursors, and that it allows the subsequent functional expression of these foreign sequences. The recent evolutionary acquisition of genes that adopt the same imprint as older, flanking genes indicates that the newly acquired genes become 'innocent bystanders' of a primary epigenetic signal causing imprinting in the PWS domain.

An infectious way to teach students about outbreaks.

PubMed

Cremin, Íde; Watson, Oliver; Heffernan, Alastair; Imai, Natsuko; Ahmed, Norin; Bivegete, Sandra; Kimani, Teresia; Kyriacou, Demetris; Mahadevan, Preveina; Mustafa, Rima; Pagoni, Panagiota; Sophiea, Marisa; Whittaker, Charlie; Beacroft, Leo; Riley, Steven; Fisher, Matthew C

2018-06-01

The study of infectious disease outbreaks is required to train today's epidemiologists. A typical way to introduce and explain key epidemiological concepts is through the analysis of a historical outbreak. There are, however, few training options that explicitly utilise real-time simulated stochastic outbreaks where the participants themselves comprise the dataset they subsequently analyse. In this paper, we present a teaching exercise in which an infectious disease outbreak is simulated over a five-day period and subsequently analysed. We iteratively developed the teaching exercise to offer additional insight into analysing an outbreak. An R package for visualisation, analysis and simulation of the outbreak data was developed to accompany the practical to reinforce learning outcomes. Computer simulations of the outbreak revealed deviations from observed dynamics, highlighting how simplifying assumptions conventionally made in mathematical models often differ from reality. Here we provide a pedagogical tool for others to use and adapt in their own settings. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity.

PubMed

Fiore, Vincenzo G; Dolan, Raymond J; Strausfeld, Nicholas J; Hirth, Frank

2015-12-19

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. © 2015 The Authors.

Evolutionarily conserved mechanisms for the selection and maintenance of behavioural activity

PubMed Central

Fiore, Vincenzo G.; Dolan, Raymond J.; Strausfeld, Nicholas J.; Hirth, Frank

2015-01-01

Survival and reproduction entail the selection of adaptive behavioural repertoires. This selection manifests as phylogenetically acquired activities that depend on evolved nervous system circuitries. Lorenz and Tinbergen already postulated that heritable behaviours and their reliable performance are specified by genetically determined programs. Here we compare the functional anatomy of the insect central complex and vertebrate basal ganglia to illustrate their role in mediating selection and maintenance of adaptive behaviours. Comparative analyses reveal that central complex and basal ganglia circuitries share comparable lineage relationships within clusters of functionally integrated neurons. These clusters are specified by genetic mechanisms that link birth time and order to their neuronal identities and functions. Their subsequent connections and associated functions are characterized by similar mechanisms that implement dimensionality reduction and transition through attractor states, whereby spatially organized parallel-projecting loops integrate and convey sensorimotor representations that select and maintain behavioural activity. In both taxa, these neural systems are modulated by dopamine signalling that also mediates memory-like processes. The multiplicity of similarities between central complex and basal ganglia suggests evolutionarily conserved computational mechanisms for action selection. We speculate that these may have originated from ancestral ground pattern circuitries present in the brain of the last common ancestor of insects and vertebrates. PMID:26554043

Executive function processes predict mobility outcomes in older adults.

PubMed

Gothe, Neha P; Fanning, Jason; Awick, Elizabeth; Chung, David; Wójcicki, Thomas R; Olson, Erin A; Mullen, Sean P; Voss, Michelle; Erickson, Kirk I; Kramer, Arthur F; McAuley, Edward

2014-02-01

To examine the relationship between performance on executive function measures and subsequent mobility outcomes in community-dwelling older adults. Randomized controlled clinical trial. Champaign-Urbana, Illinois. Community-dwelling older adults (N = 179; mean age 66.4). A 12-month exercise trial with two arms: an aerobic exercise group and a stretching and strengthening group. Established cognitive tests of executive function (flanker task, task switching, and a dual-task paradigm) and the Wisconsin card sort test. Mobility was assessed using the timed 8-foot up and go test and times to climb up and down a flight of stairs. Participants completed the cognitive tests at baseline and the mobility measures at baseline and after 12 months of the intervention. Multiple regression analyses were conducted to determine whether baseline executive function predicted postintervention functional performance after controlling for age, sex, education, cardiorespiratory fitness, and baseline mobility levels. Selective baseline executive function measurements, particularly performance on the flanker task (β = 0.15-0.17) and the Wisconsin card sort test (β = 0.11-0.16) consistently predicted mobility outcomes at 12 months. The estimates were in the expected direction, such that better baseline performance on the executive function measures predicted better performance on the timed mobility tests independent of intervention. Executive functions of inhibitory control, mental set shifting, and attentional flexibility were predictive of functional mobility. Given the literature associating mobility limitations with disability, morbidity, and mortality, these results are important for understanding the antecedents to poor mobility function that well-designed interventions to improve cognitive performance can attenuate. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

40 CFR 439.1 - General definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... bacteria) and subsequently to nitrates (via Nitrobacter bacteria). Criteria for determining the... bacteria; and analyses of the nitrogen balance demonstrating a reduction in the concentration of ammonia or...

40 CFR 439.1 - General definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... bacteria) and subsequently to nitrates (via Nitrobacter bacteria). Criteria for determining the... bacteria; and analyses of the nitrogen balance demonstrating a reduction in the concentration of ammonia or...

Impact of primary care depression intervention on employment and workplace conflict outcomes: is value added?

PubMed

Smith, Jeffrey L; Rost, Kathryn M; Nutting, Paul A; Libby, Anne M; Elliott, Carl E; Pyne, Jeffrey M

2002-03-01

Depression causes significant functional impairment in sufferers and often leads to adverse employment outcomes for working individuals. Recovery from depression has been associated with better employment outcomes at one year. The study s goals were to assess a primary care depression intervention s impact on subsequent employment and workplace conflict outcomes in employed patients with depression. In 1996-1997, the study enrolled 262 employed patients with depression from twelve primary care practices located across ten U.S. states; 219 (84%) of the patients were followed at one year. Intent-to-treat analyses assessing intervention effects on subsequent employment and workplace conflict were conducted using logistic regression models controlling for individual clinical and sociodemographic characteristics, job classification and local employment conditions. To meet criteria for subsequent employment, persons working full-time at baseline had to report they were working full-time at follow-up and persons working part-time at baseline had to report working part-/full-time at follow-up. Workplace conflict was measured by asking patients employed at follow-up whether, in the past year, they had arguments or other difficulties with people at work . Findings showed that 92.1% of intervention patients met criteria for subsequent employment at one year, versus 82.0% of usual care patients (c2=4.42, p=.04). Intervention patients were less likely than usual care patients to report workplace conflict in the year following baseline (8.1% vs. 18.9%, respectively; c2=4.11; p=.04). The intervention s effect on subsequent employment was not mediated by its effect on workplace conflict. The intervention significantly improved employment outcomes and reduced workplace conflict in depressed, employed persons at one year. Economic implications for employers related to reduced turnover costs, for workers related to retained earnings, and for governments related to reduced unemployment expenditures and increased tax receipts may be considerable. Although similar primary care depression interventions have been shown to produce comparable effects on subsequent employment at one year, replications in larger samples of depressed, employed patients in different economic climates may be necessary to increase the generalizability and precision of estimates. Primary care interventions that enhance depression treatment and improve clinical outcomes can contribute meaningful added value to society by improving employment and workplace outcomes. Federal/state governments may realize economic benefits from reduced unemployment expenditures and increased tax receipts should primary care depression interventions that improve employment outcomes be broadly disseminated. Policy initiatives to increase the dissemination of such interventions may be an innovative approach for improving labor force participation by depressed individuals. Formal cost-benefit analyses are needed to explore whether economic benefits to societal stakeholders from these and other labor outcomes equal or exceed the incremental costs of disseminating similar primary care interventions nationally. Researchers in other nations may wish to consider investigating the impact primary care depression interventions might have on employment and workplace outcomes in their countries.

Metagenomic Exploration of Viruses throughout the Indian Ocean

PubMed Central

Lorenzi, Hernan A.; Fadrosh, Douglas W.; Brami, Daniel; Thiagarajan, Mathangi; McCrow, John P.; Tovchigrechko, Andrey; Yooseph, Shibu; Venter, J. Craig

2012-01-01

The characterization of global marine microbial taxonomic and functional diversity is a primary goal of the Global Ocean Sampling Expedition. As part of this study, 19 water samples were collected aboard the Sorcerer II sailing vessel from the southern Indian Ocean in an effort to more thoroughly understand the lifestyle strategies of the microbial inhabitants of this ultra-oligotrophic region. No investigations of whole virioplankton assemblages have been conducted on waters collected from the Indian Ocean or across multiple size fractions thus far. Therefore, the goals of this study were to examine the effect of size fractionation on viral consortia structure and function and understand the diversity and functional potential of the Indian Ocean virome. Five samples were selected for comprehensive metagenomic exploration; and sequencing was performed on the microbes captured on 3.0-, 0.8- and 0.1 µm membrane filters as well as the viral fraction (<0.1 µm). Phylogenetic approaches were also used to identify predicted proteins of viral origin in the larger fractions of data from all Indian Ocean samples, which were included in subsequent metagenomic analyses. Taxonomic profiling of viral sequences suggested that size fractionation of marine microbial communities enriches for specific groups of viruses within the different size classes and functional characterization further substantiated this observation. Functional analyses also revealed a relative enrichment for metabolic proteins of viral origin that potentially reflect the physiological condition of host cells in the Indian Ocean including those involved in nitrogen metabolism and oxidative phosphorylation. A novel classification method, MGTAXA, was used to assess virus-host relationships in the Indian Ocean by predicting the taxonomy of putative host genera, with Prochlorococcus, Acanthochlois and members of the SAR86 cluster comprising the most abundant predictions. This is the first study to holistically explore virioplankton dynamics across multiple size classes and provides unprecedented insight into virus diversity, metabolic potential and virus-host interactions. PMID:23082107

Exchange of Stuttering From Function Words to Content Words With Age

PubMed Central

Howell, Peter; Au-Yeung, James; Sackin, Stevie

2007-01-01

Dysfluencies on function words in the speech of people who stutter mainly occur when function words precede, rather than follow, content words (Au-Yeung, Howell, & Pilgrim, 1998). It is hypothesized that such function word dysfluencies occur when the plan for the subsequent content word is not ready for execution. Repetition and hesitation on the function words buys time to complete the plan for the content word. Stuttering arises when speakers abandon the use of this delaying strategy and carry on, attempting production of the subsequent, partly prepared content word. To test these hypotheses, the relationship between dysfluency on function and content words was investigated in the spontaneous speech of 51 people who stutter and 68 people who do not stutter. These participants were subdivided into the following age groups: 2–6-year-olds, 7–9-year-olds, 10–12-year-olds, teenagers (13–18 years), and adults (20–40 years). Very few dysfluencies occurred for either fluency group on function words that occupied a position after a content word. For both fluency groups, dysfluency within each phonological word occurred predominantly on either the function word preceding the content word or on the content word itself, but not both. Fluent speakers had a higher percentage of dysfluency on initial function words than content words. Whether dysfluency occurred on initial function words or content words changed over age groups for speakers who stutter. For the 2–6-year-old speakers that stutter, there was a higher percentage of dysfluencies on initial function words than content words. In subsequent age groups, dysfluency decreased on function words and increased on content words. These data are interpreted as suggesting that fluent speakers use repetition of function words to delay production of the subsequent content words, whereas people who stutter carry on and attempt a content word on the basis of an incomplete plan. PMID:10229451

Root diversity in alpine plants: root length, tensile strength and plant age

NASA Astrophysics Data System (ADS)

Pohl, M.; Stroude, R.; Körner, C.; Buttler, A.; Rixen, C.

2009-04-01

A high diversity of plant species and functional groups is hypothesised to increase the diversity of root types and their subsequent effects for soil stability. However, even basic data on root characteristics of alpine plants are very scarce. Therefore, we determined important root characteristics of 13 plant species from different functional groups, i.e. grasses, herbs and shrubs. We excavated the whole root systems of 62 plants from a machine-graded ski slope at 2625 m a.s.l. and analysed the rooting depth, the horizontal root extension, root length and diameter. Single roots of plant species were tested for tensile strength. The age of herbs and shrubs was determined by growth-ring analysis. Root characteristics varied considerably between both plant species and functional groups. The rooting depth of different species ranged from 7.2 ± 0.97 cm to 20.5 ± 2.33 cm, but was significantly larger in the herb Geum reptans (70.8 ± 10.75 cm). The woody species Salix breviserrata reached the highest horizontal root extensions (96.8 ± 25.5 cm). Most plants had their longest roots in fine diameter classes (0.5

Control of nucleus accumbens activity with neurofeedback

PubMed Central

Greer, Stephanie M.; Trujillo, Andrew J.; Glover, Gary H.; Knutson, Brian

2014-01-01

The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as “neurofeedback.” In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive arousal affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function. PMID:24705203

Examining the concurrent and longitudinal relationship between diurnal cortisol rhythms and conduct problems during childhood.

PubMed

Salis, Katie Lee; Bernard, Kristin; Black, Sarah R; Dougherty, Lea R; Klein, Daniel

2016-09-01

Previous literature indicates that both hypoactivity and hyperactivity of the HPA axis may be related to conduct disorder and externalizing behaviors in young children. Using a longitudinal sample of 283 typically-developing children, the current study examined both the concurrent and the longitudinal association between HPA functioning and externalizing behavior problems, such as conduct problems. Diurnal cortisol rhythms and externalizing problems were assessed at ages 6 and 9. Results suggest that concurrent HPA functioning is not significantly related to externalizing behavior at ages 6 or 9. However, more blunted cortisol rhythms at age 6 (less change across the day from morning to evening) predicted a greater increase in externalizing behavior between age 6 and age 9 than did steeper cortisol rhythms. Further analyses revealed that this association was driven by conduct problems and aggressive behavior, rather than attention problems. The relationship between HPA functioning and subsequent externalizing behavior in children adds to the limited longitudinal work on this topic, suggesting that the association changes over time. These results may serve to clarify the inconsistencies in the cross-sectional literature, particularly with respect to young school-age children. Copyright © 2016 Elsevier Ltd. All rights reserved.

Examining the Concurrent and Longitudinal Relationship between Diurnal Cortisol Rhythms and Conduct Problems during Childhood

PubMed Central

Salis, Katie Lee; Bernard, Kristin; Black, Sarah R.; Dougherty, Lea R.; Klein, Daniel

2017-01-01

Previous literature indicates that both hypoactivity and hyperactivity of the HPA axis may be related to conduct disorder and externalizing behaviors in young children. Using a longitudinal sample of 283 typically-developing children, the current study examined both the concurrent and the longitudinal association between HPA functioning and externalizing behavior problems, such as conduct problems. Diurnal cortisol rhythms and externalizing problems were assessed at ages 6 and 9. Results suggest that concurrent HPA functioning is not significantly related to externalizing behavior at ages 6 or 9. However, more blunted cortisol rhythms at age 6 (less change across the day from morning to evening) predicted a greater increase in externalizing behavior between age 6 and age 9 than did steeper cortisol rhythms. Further analyses revealed that this association was driven by conduct problems and aggressive behavior, rather than attention problems. The relationship between HPA functioning and subsequent externalizing behavior in children adds to the limited longitudinal work on this topic, suggesting that the association changes over time. These results may serve to clarify the inconsistencies in the cross-sectional literature, particularly with respect to young school-age children. PMID:27266968

Vitamin supplementation by gut symbionts ensures metabolic homeostasis in an insect host

PubMed Central

Salem, Hassan; Bauer, Eugen; Strauss, Anja S.; Vogel, Heiko; Marz, Manja; Kaltenpoth, Martin

2014-01-01

Despite the demonstrated functional importance of gut microbes, our understanding of how animals regulate their metabolism in response to nutritionally beneficial symbionts remains limited. Here, we elucidate the functional importance of the African cotton stainer's (Dysdercus fasciatus) association with two actinobacterial gut symbionts and subsequently examine the insect's transcriptional response following symbiont elimination. In line with bioassays demonstrating the symbionts' contribution towards host fitness through the supplementation of B vitamins, comparative transcriptomic analyses of genes involved in import and processing of B vitamins revealed an upregulation of gene expression in aposymbiotic (symbiont-free) compared with symbiotic individuals; an expression pattern that is indicative of B vitamin deficiency in animals. Normal expression levels of these genes, however, can be restored by either artificial supplementation of B vitamins into the insect's diet or reinfection with the actinobacterial symbionts. Furthermore, the functional characterization of the differentially expressed thiamine transporter 2 through heterologous expression in Xenopus laevis oocytes confirms its role in cellular uptake of vitamin B1. These findings demonstrate that despite an extracellular localization, beneficial gut microbes can be integral to the host's metabolic homeostasis, reminiscent of bacteriome-localized intracellular mutualists. PMID:25339726

Leisure time physical activity and subsequent physical and mental health functioning among midlife Finnish, British and Japanese employees: a follow-up study in three occupational cohorts.

PubMed

Lahti, Jouni; Sabia, Séverine; Singh-Manoux, Archana; Kivimäki, Mika; Tatsuse, Takashi; Yamada, Masaaki; Sekine, Michikazu; Lallukka, Tea

2016-01-06

The aim of this study was to examine whether leisure time physical activity contributes to subsequent physical and mental health functioning among midlife employees. The associations were tested in three occupational cohorts from Finland, Britain and Japan. Cohort study. Finland, Britain and Japan. Prospective employee cohorts from the Finnish Helsinki Health Study (2000-2002 and 2007, n=5958), British Whitehall II study (1997-1999 and 2003-2004, n=4142) and Japanese Civil Servants Study (1998-1999 and 2003, n=1768) were used. Leisure time physical activity was classified into three groups: inactive, moderately active and vigorously active. Mean scores of physical and mental health functioning (SF-36) at follow-up were examined. Physical activity was associated with better subsequent physical health functioning in all three cohorts, however, with varying magnitude and some gender differences. Differences were the clearest among Finnish women (inactive: 46.0, vigorously active: 49.5) and men (inactive: 47.8, active vigorous: 51.1) and British women (inactive: 47.3, active vigorous: 50.4). In mental health functioning, the differences were generally smaller and not that clearly related to the intensity of physical activity. Emerging differences in health functioning were relatively small. Vigorous physical activity was associated with better subsequent physical health functioning in all three cohorts with varying magnitude. For mental health functioning, the intensity of physical activity was less important. Promoting leisure time physical activity may prove useful for the maintenance of health functioning among midlife employees. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Origin and functional diversification of an amphibian defense peptide arsenal.

PubMed

Roelants, Kim; Fry, Bryan G; Ye, Lumeng; Stijlemans, Benoit; Brys, Lea; Kok, Philippe; Clynen, Elke; Schoofs, Liliane; Cornelis, Pierre; Bossuyt, Franky

2013-01-01

The skin secretion of many amphibians contains an arsenal of bioactive molecules, including hormone-like peptides (HLPs) acting as defense toxins against predators, and antimicrobial peptides (AMPs) providing protection against infectious microorganisms. Several amphibian taxa seem to have independently acquired the genes to produce skin-secreted peptide arsenals, but it remains unknown how these originated from a non-defensive ancestral gene and evolved diverse defense functions against predators and pathogens. We conducted transcriptome, genome, peptidome and phylogenetic analyses to chart the full gene repertoire underlying the defense peptide arsenal of the frog Silurana tropicalis and reconstruct its evolutionary history. Our study uncovers a cluster of 13 transcriptionally active genes, together encoding up to 19 peptides, including diverse HLP homologues and AMPs. This gene cluster arose from a duplicated gastrointestinal hormone gene that attained a HLP-like defense function after major remodeling of its promoter region. Instead, new defense functions, including antimicrobial activity, arose by mutation of the precursor proteins, resulting in the proteolytic processing of secondary peptides alongside the original ones. Although gene duplication did not trigger functional innovation, it may have subsequently facilitated the convergent loss of the original function in multiple gene lineages (subfunctionalization), completing their transformation from HLP gene to AMP gene. The processing of multiple peptides from a single precursor entails a mechanism through which peptide-encoding genes may establish new functions without the need for gene duplication to avoid adaptive conflicts with older ones.

Disruption to functional networks in neonates with perinatal brain injury predicts motor skills at 8 months.

PubMed

Linke, Annika C; Wild, Conor; Zubiaurre-Elorza, Leire; Herzmann, Charlotte; Duffy, Hester; Han, Victor K; Lee, David S C; Cusack, Rhodri

2018-01-01

Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries. Infants ( n  = 65, included in final analyses: n  = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (premature vs. term), and on whether neuropathology was diagnosed from structural MRI. Functional brain networks and a measure of disruption to functional connectivity were obtained from 14 min of fcMRI acquired during natural sleep at term-equivalent age. Disruption to connectivity of the somatomotor and frontoparietal executive networks predicted motor impairment at 4 and 8 months. This disruption in functional connectivity was not found to be driven by differences between clinical groups, or by any of the specific measures we captured to describe the clinical course. fcMRI was predictive over and above other clinical measures available at discharge from the NICU, including structural MRI. Motor learning was affected by disruption to somatomotor networks, but also frontoparietal executive networks, which supports the functional importance of these networks in early development. Disruption to these two networks might be best addressed by distinct intervention strategies.

Origin and Functional Diversification of an Amphibian Defense Peptide Arsenal

PubMed Central

Roelants, Kim; Fry, Bryan G.; Ye, Lumeng; Stijlemans, Benoit; Brys, Lea; Kok, Philippe; Clynen, Elke; Schoofs, Liliane; Cornelis, Pierre; Bossuyt, Franky

2013-01-01

The skin secretion of many amphibians contains an arsenal of bioactive molecules, including hormone-like peptides (HLPs) acting as defense toxins against predators, and antimicrobial peptides (AMPs) providing protection against infectious microorganisms. Several amphibian taxa seem to have independently acquired the genes to produce skin-secreted peptide arsenals, but it remains unknown how these originated from a non-defensive ancestral gene and evolved diverse defense functions against predators and pathogens. We conducted transcriptome, genome, peptidome and phylogenetic analyses to chart the full gene repertoire underlying the defense peptide arsenal of the frog Silurana tropicalis and reconstruct its evolutionary history. Our study uncovers a cluster of 13 transcriptionally active genes, together encoding up to 19 peptides, including diverse HLP homologues and AMPs. This gene cluster arose from a duplicated gastrointestinal hormone gene that attained a HLP-like defense function after major remodeling of its promoter region. Instead, new defense functions, including antimicrobial activity, arose by mutation of the precursor proteins, resulting in the proteolytic processing of secondary peptides alongside the original ones. Although gene duplication did not trigger functional innovation, it may have subsequently facilitated the convergent loss of the original function in multiple gene lineages (subfunctionalization), completing their transformation from HLP gene to AMP gene. The processing of multiple peptides from a single precursor entails a mechanism through which peptide-encoding genes may establish new functions without the need for gene duplication to avoid adaptive conflicts with older ones. PMID:23935531

Routine postoperative CT-scans after burr hole trepanation for chronic subdural hematoma - better before or after drainage removal?

PubMed

Brokinkel, Benjamin; Ewelt, Christian; Holling, Markus; Hesselmann, Volker; Heindel, Walter Leonard; Stummer, Walter; Fischer, Bernhard Robert

2013-01-01

To evaluate timing of scheduled CT-scans after burr hole trepanation for chronic subdural hematoma (cSDH). 131 patients with primary cSDH were included. Scheduled CT-scans were performed after burr hole trepanation and placement of a subdural drain. The influence of CT-scanning with or without indwelling drain was analysed regarding subsequent surgery and CT-scans, duration of hospitalization, short- and middle-term follow up by single factor analyses. Subgroup analyses were performed for patients receiving anticoagulant drugs. Median age was 74 years. Routine CT-scans with indwelling drainage were not shown to be beneficial regarding subsequent burr hole trepanations (p=0.243), craniotomies (p=1.000) and outcome at discharge (p=0.297). Mean duration of hospitalization (11 vs. 8 days, p=0.013) was significantly longer and number of subsequent CT-scans was higher when CT scan was performed with indwelling drain (2.3 vs. 1.4, p=0.001). In middle-term follow-up, beneficial effects of CT-scanning with inlaying drainage could neither be shown. Moreover, advantageous effects of CT-scans with indwelling drains could neither be shown for patients receiving anticoagulant drugs. Scheduled postoperative cranial imaging with indwelling drains was not shown to be beneficial and misses information of intracranial damage inflicted by removal of drains. We thus recommend CT-scanning after drainage removal.

Processing communications events in parallel active messaging interface by awakening thread from wait state

DOEpatents

Archer, Charles J; Blocksome, Michael A; Ratterman, Joseph D; Smith, Brian E

2013-10-22

Processing data communications events in a parallel active messaging interface (`PAMI`) of a parallel computer that includes compute nodes that execute a parallel application, with the PAMI including data communications endpoints, and the endpoints are coupled for data communications through the PAMI and through other data communications resources, including determining by an advance function that there are no actionable data communications events pending for its context, placing by the advance function its thread of execution into a wait state, waiting for a subsequent data communications event for the context; responsive to occurrence of a subsequent data communications event for the context, awakening by the thread from the wait state; and processing by the advance function the subsequent data communications event now pending for the context.

Efficient production and purification of functional bacteriorhodopsin with a wheat-germ cell-free system and a combination of Fos-choline and CHAPS detergents.

PubMed

Genji, Takahisa; Nozawa, Akira; Tozawa, Yuzuru

2010-10-01

Cell-free translation is one potential approach to the production of functional transmembrane proteins. We have now examined various detergents as supplements to a wheat-germ cell-free system in order to optimize the production and subsequent purification of a functional model transmembrane protein, bacteriorhodopsin. We found that Fos-choline and CHAPS detergents counteracted each other's inhibitory effects on cell-free translation activity and thereby allowed the efficient production and subsequent purification of functional bacteriorhodopsin in high yield. Copyright © 2010 Elsevier Inc. All rights reserved.

Genetic and functional characterization of a novel meta-pathway for degradation of naringenin in Herbaspirillum seropedicae SmR1.

PubMed

Maria Marin, Anelis; de la Torre, Jésus; Ricardo Marques Oliveira, Alfredo; Barison, Andersson; Satie Chubatsu, Leda; Adele Monteiro, Rose; de Oliveira Pedrosa, Fabio; Maltempi de Souza, Emanuel; Wassem, Roseli; Duque, Estrella; Ramos, Juan-Luis

2016-12-01

In this study, a random mutant library of Herbaspirillum seropedicae SmR1 was constructed by Tn5 insertion and a mutant incapable of utilizing naringenin as a carbon source was isolated. The Tn5 transposon was found to be inserted in the fdeE gene (Hsero_1007), which encodes a monooxygenase. Two other mutant strains in fdeC (Hsero_1005) and fdeG (Hsero_1009) genes coding for a dioxygenase and a putative cyclase, respectively, were obtained by site-directed mutagenesis and then characterized. Liquid Chromatography coupled to mass spectrometry (LC-MS)/MS analyses of culture supernatant from the fdeE mutant strain revealed that naringenin remained unaltered, suggesting that the FdeE protein is involved in the initial step of naringenin degradation. LC-MS/MS analyses of culture supernatants from the wild-type (SmR1) and FdeC deficient mutant suggested that in H. seropedicae SmR1 naringenin is first mono-oxygenated by the FdeE protein, to produce 5,7,8-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydro-4H-chromen-4-one, that is subsequently dioxygenated and cleaved at the A-ring by the FdeC dioxygenase, since the latter compound accumulated in the fdeC strain. After meta-cleavage of the A-ring, the subsequent metabolic steps generate oxaloacetic acid that is metabolized via the tricarboxylic acid cycle. This bacterium can also modify naringenin by attaching a glycosyl group to the B-ring or a methoxy group to the A-ring, leading to the generation of dead-end products. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

CALCMIN - an EXCEL™ Visual Basic application for calculating mineral structural formulae from electron microprobe analyses

NASA Astrophysics Data System (ADS)

Brandelik, Andreas

2009-07-01

CALCMIN, an open source Visual Basic program, was implemented in EXCEL™. The program was primarily developed to support geoscientists in their routine task of calculating structural formulae of minerals on the basis of chemical analysis mainly obtained by electron microprobe (EMP) techniques. Calculation programs for various minerals are already included in the form of sub-routines. These routines are arranged in separate modules containing a minimum of code. The architecture of CALCMIN allows the user to easily develop new calculation routines or modify existing routines with little knowledge of programming techniques. By means of a simple mouse-click, the program automatically generates a rudimentary framework of code using the object model of the Visual Basic Editor (VBE). Within this framework simple commands and functions, which are provided by the program, can be used, for example, to perform various normalization procedures or to output the results of the computations. For the clarity of the code, element symbols are used as variables initialized by the program automatically. CALCMIN does not set any boundaries in complexity of the code used, resulting in a wide range of possible applications. Thus, matrix and optimization methods can be included, for instance, to determine end member contents for subsequent thermodynamic calculations. Diverse input procedures are provided, such as the automated read-in of output files created by the EMP. Furthermore, a subsequent filter routine enables the user to extract specific analyses in order to use them for a corresponding calculation routine. An event-driven, interactive operating mode was selected for easy application of the program. CALCMIN leads the user from the beginning to the end of the calculation process.

Early Childhood Activism, Minor Politics and Resuscitating Vision: A Tentative Foray into the Use of "Intersections" to Influence Early Childhood Policy

ERIC Educational Resources Information Center

Press, Frances; Skattebol, Jen

2007-01-01

Many postmodern and post-structural analyses of government policies affecting early childhood education stress the hegemonic nature of neo-liberalism and subsequently primarily focus upon identifying the manifestation of neo-liberal values in such interventions. An unintended and stultifying consequence of such analyses is, at times, to close off…

Differences in Brain Activity during a Verbal Associative Memory Encoding Task in High- and Low-fit Adolescents

PubMed Central

Herting, Megan M.; Nagel, Bonnie J.

2013-01-01

Aerobic fitness is associated with better memory performance as well as larger volumes in memory-related brain regions in children, adolescents, and elderly. It is unclear if aerobic exercise also influences learning and memory functional neural circuitry. Here, we examine brain activity in 17 high-fit (HF) and 17 low-fit (LF) adolescents during a subsequent memory encoding paradigm using fMRI. Despite similar memory performance, HF and LF youth displayed a number of differences in memory-related and default mode (DMN) brain regions during encoding later remembered versus forgotten word pairs. Specifically, HF youth displayed robust deactivation in DMN areas, including the ventral medial PFC and posterior cingulate cortex, whereas LF youth did not show this pattern. Furthermore, LF youth showed greater bilateral hippocampal and right superior frontal gyrus activation during encoding of later remembered versus forgotten word pairs. Follow-up task-dependent functional correlational analyses showed differences in hippocampus and DMN activity coupling during successful encoding between the groups, suggesting aerobic fitness during adolescents may impact functional connectivity of the hippocampus and DMN during memory encoding. To our knowledge, this study is the first to examine the influence of aerobic fitness on hippocampal function and memory-related neural circuitry using fMRI. Taken together with previous research, these findings suggest aerobic fitness can influence not only memory-related brain structure, but also brain function. PMID:23249350

Technical advance: live-imaging analysis of human dendritic cell migrating behavior under the influence of immune-stimulating reagents in an organotypic model of lung.

PubMed

Nguyen Hoang, Anh Thu; Chen, Puran; Björnfot, Sofia; Högstrand, Kari; Lock, John G; Grandien, Alf; Coles, Mark; Svensson, Mattias

2014-09-01

This manuscript describes technical advances allowing manipulation and quantitative analyses of human DC migratory behavior in lung epithelial tissue. DCs are hematopoietic cells essential for the maintenance of tissue homeostasis and the induction of tissue-specific immune responses. Important functions include cytokine production and migration in response to infection for the induction of proper immune responses. To design appropriate strategies to exploit human DC functional properties in lung tissue for the purpose of clinical evaluation, e.g., candidate vaccination and immunotherapy strategies, we have developed a live-imaging assay based on our previously described organotypic model of the human lung. This assay allows provocations and subsequent quantitative investigations of DC functional properties under conditions mimicking morphological and functional features of the in vivo parental tissue. We present protocols to set up and prepare tissue models for 4D (x, y, z, time) fluorescence-imaging analysis that allow spatial and temporal studies of human DCs in live epithelial tissue, followed by flow cytometry analysis of DCs retrieved from digested tissue models. This model system can be useful for elucidating incompletely defined pathways controlling DC functional responses to infection and inflammation in lung epithelial tissue, as well as the efficacy of locally administered candidate interventions. © 2014 Society for Leukocyte Biology.

The Influence of Treatment Attendance on Subsequent Aggression among Severely Mentally Ill Substance Abusers

PubMed Central

Zhuo, Yue; Bradizza, Clara M.; Maisto, Stephen A.

2014-01-01

The interrelationships between severe mental illness, substance use, and aggression are of longstanding importance with implications for community treatment programs, treatment research and public policy. Through the analysis of longitudinal data collected from 278 patients over a 6-month period following admission to an outpatient dual diagnosis treatment program, this study examined the association between dual diagnosis treatment attendance and subsequent aggression among individuals diagnosed with both a severe mental illness and a substance use disorder. We also tested substance use and psychiatric symptoms as mediators of this treatment-aggression relationship. The results of structural equation modeling analyses indicated that dual diagnosis treatment was associated with lower levels of subsequent aggression. Mediational analyses indicated that greater treatment involvement was associated with reduced substance use, which was associated with lower levels of aggression; thus, substance use was found to mediate the relationship between dual diagnosis treatment and aggression. Surprisingly, severity of psychiatric symptoms did not predict later aggression. These findings suggest that targeting substance use reduction in treatment may have the additional benefit of reducing the risk of later aggression among dual diagnosis patients. PMID:25124261

Representing and organizing information to describe the lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health (ICF): a discussion paper.

PubMed

Geyh, Szilvia; Schwegler, Urban; Peter, Claudio; Müller, Rachel

2018-03-06

To discuss the representation and organization of information describing persons' lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health, using spinal cord injury as a case in point for disability. The scientific literature was reviewed, discussion rounds conducted, and qualitative secondary analyses of data carried out using an iterative inductive-deductive approach. Conceptual considerations are explicated that distinguish the personal factors perspective from other components of the International Classification of Functioning, Disability and Health. A representation structure is developed that organizes health-related concepts describing the internal context of functioning. Concepts are organized as individual facts, subjective experiences, and recurrent patterns of experience and behavior specifying 7 areas and 211 concept groups. The article calls for further scientific debate on the perspective of personal factors in the light of the International Classification of Functioning, Disability and Health. A structure that organizes concepts in relation to a personal factors perspective can enhance the comprehensiveness, transparency and standardization of health information, and contribute to the empowerment of persons with disabilities. Implications for rehabilitation The present study collected data from scientific literature reviews, discussion rounds and qualitative secondary analyses in order to develop a representation and organization of information describing persons' lived experience of health from a personal factors perspective in the light of the International Classification of Functioning, Disability and Health. The following representation structure for health-related information from a personal factors perspective was developed: (i) Individuals facts (i.e., socio-demographical factors, position in the immediate social and physical context, personal history and biography), (ii) subjective experience (i.e., feelings, thoughts and beliefs, motives), and (iii) recurrent patterns of experience (i.e., feelings, thoughts and beliefs) and behavior. With this study, we aim to stimulate further scientific discussion about the personal factors component in the International Classification of Functioning, Disability and Health, including its application and subsequent validation for potential implementation into clinical practice.

77 FR 56172 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... high tensile standing stress, resulting from dry fit axle assembly method. Improvement has been introduced subsequently with a grease fit axle assembly method. Fatigue and damage tolerance analyses were...

Structural tailoring of counter rotation propfans

NASA Technical Reports Server (NTRS)

Brown, Kenneth W.; Hopkins, D. A.

1989-01-01

The STAT program was designed for the optimization of single rotation, tractor propfan designs. New propfan designs, however, generally consist of two counter rotating propfan rotors. STAT is constructed to contain two levels of analysis. An interior loop, consisting of accurate, efficient approximate analyses, is used to perform the primary propfan optimization. Once an optimum design has been obtained, a series of refined analyses are conducted. These analyses, while too computer time expensive for the optimization loop, are of sufficient accuracy to validate the optimized design. Should the design prove to be unacceptable, provisions are made for recalibration of the approximate analyses, for subsequent reoptimization.

Hierarchical Traces for Reduced NSM Memory Requirements

NASA Astrophysics Data System (ADS)

Dahl, Torbjørn S.

This paper presents work on using hierarchical long term memory to reduce the memory requirements of nearest sequence memory (NSM) learning, a previously published, instance-based reinforcement learning algorithm. A hierarchical memory representation reduces the memory requirements by allowing traces to share common sub-sequences. We present moderated mechanisms for estimating discounted future rewards and for dealing with hidden state using hierarchical memory. We also present an experimental analysis of how the sub-sequence length affects the memory compression achieved and show that the reduced memory requirements do not effect the speed of learning. Finally, we analyse and discuss the persistence of the sub-sequences independent of specific trace instances.

Unravelling the Intrinsic Functional Organization of the Human Striatum: A Parcellation and Connectivity Study Based on Resting-State fMRI

PubMed Central

Jung, Wi Hoon; Jang, Joon Hwan; Park, Jin Woo; Kim, Euitae; Goo, Eun-Hoe; Im, Oh-Soo; Kwon, Jun Soo

2014-01-01

As the main input hub of the basal ganglia, the striatum receives projections from the cerebral cortex. Many studies have provided evidence for multiple parallel corticostriatal loops based on the structural and functional connectivity profiles of the human striatum. A recent resting-state fMRI study revealed the topography of striatum by assigning each voxel in the striatum to its most strongly correlated cortical network among the cognitive, affective, and motor networks. However, it remains unclear what patterns of striatal parcellation would result from performing the clustering without subsequent assignment to cortical networks. Thus, we applied unsupervised clustering algorithms to parcellate the human striatum based on its functional connectivity patterns to other brain regions without any anatomically or functionally defined cortical targets. Functional connectivity maps of striatal subdivisions, identified through clustering analyses, were also computed. Our findings were consistent with recent accounts of the functional distinctions of the striatum as well as with recent studies about its functional and anatomical connectivity. For example, we found functional connections between dorsal and ventral striatal clusters and the areas involved in cognitive and affective processes, respectively, and between rostral and caudal putamen clusters and the areas involved in cognitive and motor processes, respectively. This study confirms prior findings, showing similar striatal parcellation patterns between the present and prior studies. Given such striking similarity, it is suggested that striatal subregions are functionally linked to cortical networks involving specific functions rather than discrete portions of cortical regions. Our findings also demonstrate that the clustering of functional connectivity patterns is a reliable feature in parcellating the striatum into anatomically and functionally meaningful subdivisions. The striatal subdivisions identified here may have important implications for understanding the relationship between corticostriatal dysfunction and various neurodegenerative and psychiatric disorders. PMID:25203441

Improved sexual and urinary function in women with sacral nerve stimulation.

PubMed

Gill, Bradley C; Swartz, Mia A; Firoozi, Farzeen; Rackley, Raymond R; Moore, Courtenay K; Goldman, Howard B; Vasavada, Sandip P

2011-01-01

  Urinary and sexual function improve following sacral nerve stimulation (SNS) for refractory overactive bladder. No significant associations between these changes have been found. Whether improvements in sexual function are independent of or secondary to improvements in urinary function remains unclear. The aim of this study was to analyze changes in urinary and sexual function in a homogeneous sample of patients undergoing SNS for urge urinary incontinence and subsequently identify associations between the two.   A prospective database was created. Enrollees underwent a full history and physical examination at the first office visit. Multiple-day voiding diaries with validated and investigator-designed questionnaires were administered at baseline and follow-up as standard implantation procedures and to assess changes in urinary and sexual function, respectively. Analyses were completed using data from patients who were sexually active at baseline and follow-up.   Statistically significant improvements in urinary and sexual function occurred according to multiple metrics. Patient global impression scales categorized all patients' urinary conditions as improved, with most being less severe. Validated urinary symptom and quality of life scores improved significantly. After treatment, most patients were incontinent less often with sexual activity and felt less restricted from sexual activity by fear of incontinence. Validated quantification of sexual function demonstrated significant improvements in overall sexual function, arousal, and satisfaction. No significant associations between changes in urinary and sexual function were noted; however, trends appeared to exist between the two.   Improved sexual function was not significantly associated with improved urinary function after SNS despite apparent trends between the two. Larger samples are required to definitively demonstrate this conclusion. © 2011 International Neuromodulation Society.

Divergent Relationships between Fecal Microbiota and Metabolome following Distinct Antibiotic-Induced Disruptions.

PubMed

Choo, Jocelyn M; Kanno, Tokuwa; Zain, Nur Masirah Mohd; Leong, Lex E X; Abell, Guy C J; Keeble, Julie E; Bruce, Kenneth D; Mason, A James; Rogers, Geraint B

2017-01-01

The intestinal microbiome plays an essential role in regulating many aspects of host physiology, and its disruption through antibiotic exposure has been implicated in the development of a range of serious pathologies. The complex metabolic relationships that exist between members of the intestinal microbiota and the potential redundancy in functional pathways mean that an integrative analysis of changes in both structure and function are needed to understand the impact of antibiotic exposure. We used a combination of next-generation sequencing and nuclear magnetic resonance (NMR) metabolomics to characterize the effects of two clinically important antibiotic treatments, ciprofloxacin and vancomycin-imipenem, on the intestinal microbiomes of female C57BL/6 mice. This assessment was performed longitudinally and encompassed both antibiotic challenge and subsequent microbiome reestablishment. Both antibiotic treatments significantly altered the microbiota and metabolite compositions of fecal pellets during challenge and recovery. Spearman's correlation analysis of microbiota and NMR data revealed that, while some metabolites could be correlated with individual operational taxonomic units (OTUs), frequently multiple OTUs were associated with a significant change in a given metabolite. Furthermore, one metabolite, arginine, can be associated with increases/decreases in different sets of OTUs under differing conditions. Taken together, these findings indicate that reliance on shifts in one data set alone will generate an incomplete picture of the functional effect of antibiotic intervention. A full mechanistic understanding will require knowledge of the baseline microbiota composition, combined with both a comparison and an integration of microbiota, metabolomics, and phenotypic data. IMPORTANCE Despite the fundamental importance of antibiotic therapies to human health, their functional impact on the intestinal microbiome and its subsequent ability to recover are poorly understood. Much research in this area has focused on changes in microbiota composition, despite the interdependency and overlapping functions of many members of the microbial community. These relationships make prediction of the functional impact of microbiota-level changes difficult, while analyses based on the metabolome alone provide relatively little insight into the taxon-level changes that underpin changes in metabolite levels. Here, we used combined microbiota and metabolome profiling to characterize changes associated with clinically important antibiotic combinations with distinct effects on the gut. Correlation analysis of changes in the metabolome and microbiota indicate that a combined approach will be essential for a mechanistic understanding of the functional impact of distinct antibiotic classes.

Impact of Medicare Advantage Prescription Drug Plan Star Ratings on Enrollment before and after Implementation of Quality-Related Bonus Payments in 2012

PubMed Central

Li, Pengxiang; Doshi, Jalpa A.

2016-01-01

Objective Since 2007, the Centers for Medicare and Medicaid Services have published 5-star quality rating measures to aid consumers in choosing Medicare Advantage Prescription Drug Plans (MAPDs). We examined the impact of these star ratings on Medicare Advantage Prescription Drug (MAPD) enrollment before and after 2012, when star ratings became tied to bonus payments for MAPDs that could be used to improve plan benefits and/or reduce premiums in the subsequent year. Methods A longitudinal design and multivariable hybrid models were used to assess whether star ratings had a direct impact on concurrent year MAPD contract enrollment (by influencing beneficiary choice) and/or an indirect impact on subsequent year MAPD contract enrollment (because ratings were linked to bonus payments). The main analysis was based on contract-year level data from 2009–2015. We compared effects of star ratings in the pre-bonus payment period (2009–2011) and post-bonus payment period (2012–2015). Extensive sensitivity analyses varied the analytic techniques, unit of analysis, and sample inclusion criteria. Similar analyses were conducted separately using stand-alone PDP contract-year data; since PDPs were not eligible for bonus payments, they served as an external comparison group. Result The main analysis included 3,866 MAPD contract-years. A change of star rating had no statistically significant effect on concurrent year enrollment in any of the pre-, post-, or pre-post combined periods. On the other hand, star rating increase was associated with a statistically significant increase in the subsequent year enrollment (a 1-star increase associated with +11,337 enrollees, p<0.001) in the post-bonus payment period but had a very small and statistically non-significant effect on subsequent year enrollment in the pre-bonus payment period. Further, the difference in effects on subsequent year enrollment was statistically significant between the pre- and post-periods (p = 0.011). Sensitivity analyses indicated that the findings were robust. No statistically significant effect of star ratings was found on concurrent or subsequent year enrollment in the pre- or post-period in the external comparison group of stand-alone PDP contracts. Conclusion Star ratings had no direct impact on concurrent year MAPD enrollment before or after the introduction of bonus payments tied to star ratings. However, after the introduction of these bonus payments, MAPD star ratings had a significant indirect impact of increasing subsequent year enrollment, likely via the reinvestment of bonuses to provide lower premiums and/or additional member benefits in the following year. PMID:27149092

Impact of Medicare Advantage Prescription Drug Plan Star Ratings on Enrollment before and after Implementation of Quality-Related Bonus Payments in 2012.

PubMed

Li, Pengxiang; Doshi, Jalpa A

2016-01-01

Since 2007, the Centers for Medicare and Medicaid Services have published 5-star quality rating measures to aid consumers in choosing Medicare Advantage Prescription Drug Plans (MAPDs). We examined the impact of these star ratings on Medicare Advantage Prescription Drug (MAPD) enrollment before and after 2012, when star ratings became tied to bonus payments for MAPDs that could be used to improve plan benefits and/or reduce premiums in the subsequent year. A longitudinal design and multivariable hybrid models were used to assess whether star ratings had a direct impact on concurrent year MAPD contract enrollment (by influencing beneficiary choice) and/or an indirect impact on subsequent year MAPD contract enrollment (because ratings were linked to bonus payments). The main analysis was based on contract-year level data from 2009-2015. We compared effects of star ratings in the pre-bonus payment period (2009-2011) and post-bonus payment period (2012-2015). Extensive sensitivity analyses varied the analytic techniques, unit of analysis, and sample inclusion criteria. Similar analyses were conducted separately using stand-alone PDP contract-year data; since PDPs were not eligible for bonus payments, they served as an external comparison group. The main analysis included 3,866 MAPD contract-years. A change of star rating had no statistically significant effect on concurrent year enrollment in any of the pre-, post-, or pre-post combined periods. On the other hand, star rating increase was associated with a statistically significant increase in the subsequent year enrollment (a 1-star increase associated with +11,337 enrollees, p<0.001) in the post-bonus payment period but had a very small and statistically non-significant effect on subsequent year enrollment in the pre-bonus payment period. Further, the difference in effects on subsequent year enrollment was statistically significant between the pre- and post-periods (p = 0.011). Sensitivity analyses indicated that the findings were robust. No statistically significant effect of star ratings was found on concurrent or subsequent year enrollment in the pre- or post-period in the external comparison group of stand-alone PDP contracts. Star ratings had no direct impact on concurrent year MAPD enrollment before or after the introduction of bonus payments tied to star ratings. However, after the introduction of these bonus payments, MAPD star ratings had a significant indirect impact of increasing subsequent year enrollment, likely via the reinvestment of bonuses to provide lower premiums and/or additional member benefits in the following year.

The direct and indirect effects of lurasidone monotherapy on functional improvement among patients with bipolar depression: results from a randomized placebo-controlled trial.

PubMed

Rajagopalan, Krithika; Bacci, Elizabeth Dansie; Wyrwich, Kathleen W; Pikalov, Andrei; Loebel, Antony

2016-12-01

Bipolar depression is characterized by depressive symptoms and impairment in many areas of functioning, including work, family, and social life. The objective of this study was to assess the independent, direct effect of lurasidone treatment on functioning improvement, and examine the indirect effect of lurasidone treatment on functioning improvement, mediated through improvements in depression symptoms. Data from a 6-week placebo-controlled trial assessing the effect of lurasidone monotherapy versus placebo in patients with bipolar depression was used. Patient functioning was measured using the Sheehan disability scale (SDS). Descriptive statistics were used to assess the effect of lurasidone on improvement on the SDS total and domain scores (work/school, social, and family life), as well as number of days lost and unproductive due to symptoms. Path analyses evaluated the total effect (β1), as well as the indirect effect (β2×β3) and direct effect (β4) of lurasidone treatment on SDS total score change, using standardized beta path coefficients and baseline scores as covariates. The direct effect of treatment on SDS total score change and indirect effects accounting for mediation through depression improvement were examined for statistical significance and magnitude using MPlus. In this 6-week trial (N = 485), change scores from baseline to 6-weeks were significantly larger for both lurasidone treatment dosage groups versus placebo on the SDS total and all three SDS domain scores (p < 0.05). Through path analyses, lurasidone treatment predicted improvement in depression (β2 = -0.33, p = 0.009), subsequently predicting improvement in functional impairment (β3 = 0.70, p < 0.001; indirect effect = -0.23). The direct effect was of medium magnitude (β4 = -0.17, p = 0.04), indicating lurasidone had a significant and direct effect on improvement in functional impairment, after accounting for depression improvement. Results demonstrated statistically significant improvement in functioning among patients on lurasidone monotherapy compared to placebo. Improvement in functioning among patients on lurasidone was largely mediated through a reduction in depression symptoms, but lurasidone also had a medium and statistically significant independent direct effect in improving functioning.

Risk perceptions and subsequent sexual behaviors after HPV vaccination in adolescents.

PubMed

Mayhew, Allison; Mullins, Tanya L Kowalczyk; Ding, Lili; Rosenthal, Susan L; Zimet, Gregory D; Morrow, Charlene; Kahn, Jessica A

2014-03-01

Concerns have been raised that human papillomavirus (HPV) vaccination could lead to altered risk perceptions and an increase in risky sexual behaviors among adolescents. The aim of this study was to assess whether adolescent risk perceptions after the first vaccine dose predicted subsequent sexual behaviors. Young women 13 to 21 years of age (N = 339) completed questionnaires immediately after HPV vaccination, and 2 and 6 months later, assessing demographic characteristics, knowledge/attitudes about HPV vaccination, risk perceptions, and sexual behaviors. Risk perceptions were measured by using 2 5-item scales assessing: (1) perceived risk of sexually transmitted infections (STI) other than HPV, and (2) perceived need for safer sexual behaviors after HPV vaccination. We assessed associations between risk perceptions at baseline and sexual behaviors over the next 6 months by using logistic regression, stratifying participants by sexual experience at baseline and age (13-15 vs. 16-21 years). Among all sexually inexperienced participants (42.5%), baseline risk perceptions were not associated with subsequent sexual initiation; in age-stratified analyses, girls 16 to 21 years of age who reported lower perceived risk for other STI (an inappropriate perception) were less likely to initiate sex (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03-0.69). Among all sexually experienced participants (57.5%) and in age-stratified analyses, baseline risk perceptions were not associated with subsequent number of sexual partners or condom use. Risk perceptions after HPV vaccination were not associated with riskier sexual behaviors over the subsequent 6 months in this study sample.

Risk Perceptions and Subsequent Sexual Behaviors After HPV Vaccination in Adolescents

PubMed Central

Mayhew, Allison; Mullins, Tanya L. Kowalczyk; Ding, Lili; Rosenthal, Susan L.; Zimet, Gregory D.; Morrow, Charlene

2014-01-01

OBJECTIVES: Concerns have been raised that human papillomavirus (HPV) vaccination could lead to altered risk perceptions and an increase in risky sexual behaviors among adolescents. The aim of this study was to assess whether adolescent risk perceptions after the first vaccine dose predicted subsequent sexual behaviors. METHODS: Young women 13 to 21 years of age (N = 339) completed questionnaires immediately after HPV vaccination, and 2 and 6 months later, assessing demographic characteristics, knowledge/attitudes about HPV vaccination, risk perceptions, and sexual behaviors. Risk perceptions were measured by using 2 5-item scales assessing: (1) perceived risk of sexually transmitted infections (STI) other than HPV, and (2) perceived need for safer sexual behaviors after HPV vaccination. We assessed associations between risk perceptions at baseline and sexual behaviors over the next 6 months by using logistic regression, stratifying participants by sexual experience at baseline and age (13–15 vs 16–21 years). RESULTS: Among all sexually inexperienced participants (42.5%), baseline risk perceptions were not associated with subsequent sexual initiation; in age-stratified analyses, girls 16 to 21 years of age who reported lower perceived risk for other STI (an inappropriate perception) were less likely to initiate sex (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.03–0.69). Among all sexually experienced participants (57.5%) and in age-stratified analyses, baseline risk perceptions were not associated with subsequent number of sexual partners or condom use. CONCLUSIONS: Risk perceptions after HPV vaccination were not associated with riskier sexual behaviors over the subsequent 6 months in this study sample. PMID:24488747

ALK5 inhibition maintains islet endothelial cell survival but does not enhance islet graft revascularisation or function.

PubMed

King, A J F; Clarkin, C E; Austin, A L F; Ajram, L; Dhunna, J K; Jamil, M O; Ditta, S I; Ibrahim, S; Raza, Z; Jones, P M

2015-01-01

Islet transplantation is a potential treatment for Type 1 diabetes but long term graft function is suboptimal. The rich supply of intraislet endothelial cells diminishes rapidly after islet isolation and culture, which affects the revascularisation rate of islets after transplantation. The ALK5 pathway inhibits endothelial cell proliferation and thus inhibiting ALK5 is a potential target for improving endothelial cell survival. The aim of the study was to establish whether ALK5 inhibition prevents the loss of intraislet endothelial cells during islet culture and thus improves the functional survival of transplanted islets by enhancing their subsequent revascularisation after implantation. Islets were cultured for 48 h in the absence or presence of 2 different ALK inhibitors: SB-431542 or A-83-01. Their vascular density after culture was analysed using immunohistochemistry. Islets pre-cultured with the ALK5 inhibitors were implanted into streptozotocin-diabetic mice for either 3 or 7 days and blood glucose concentrations were monitored and vascular densities of the grafts were analysed. Islets cultured with ALK5 inhibitors had higher vascular densities than control-cultured islets. Three days after implantation, endothelial cell numbers in islet grafts were minimal, irrespective of treatment during culture. Seven days after implantation, endothelial cells were evident within the islet grafts but there was no difference between control-cultured islets and islets pre-treated with an ALK5 inhibitor. Blood glucose concentrations were no different between the treatment groups. In conclusion, inhibition of ALK5 improved intraislet endothelial cell numbers after islet culture, but this effect was lost in the early post-transplantation period. © Georg Thieme Verlag KG Stuttgart · New York.

Direct targeting of SUZ12/ROCK2 by miR-200b/c inhibits cholangiocarcinoma tumourigenesis and metastasis

PubMed Central

Peng, F; Jiang, J; Yu, Y; Tian, R; Guo, X; Li, X; Shen, M; Xu, M; Zhu, F; Shi, C; Hu, J; Wang, M; Qin, R

2013-01-01

Background: The multidrug resistance and distant metastasis of cholangiocarcinoma result in high postoperative recurrence and low long-term survival rates. It has been demonstrated that the ectopic expression of miR-200 suppresses the multidrug resistance and metastasis of cancer. However, the expression and function of miR-200 in cholangiocarcinoma has not yet been described. Methods: In this study, we identified dysregulated microRNAs (miRNAs, miR) in cholangiocarcinoma tissue by microarray analysis, and subsequent real-time PCR and northern blot analyses validated the expression of candidate miR. We performed functional analyses and investigated the relationship between miR-200b/c expression and the properties of cholangiocarcinoma cells. A dual luciferase assay was applied to examine the effect of miRNAs on the 3′-UTR of target genes, and we demonstrated the function of the target gene by siRNA transfection identifying the downstream pathway via western blotting. Results: We found significantly downregulated expression of four miR-200 family members (miR-200a/b/c/429) and then confirmed that ectopic miR-200b/200c inhibits the migration and invasion of cholangiocarcinoma cells both in vitro and in vivo. We found that miR-200b/c influenced the tumourigenesis of cholangiocarcinoma cells including their tumour-initiating capacity, sphere formation, and drug resistance. We further found that miR-200b/c regulated migration and invasion capacities by directly targeting rho-kinase 2 and regulated tumorigenic properties by directly targeting SUZ12 (a subunit of a polycomb repressor complex). Conclusion: Our study shows that miR-200b/c has a critical role in the regulation of the tumorigenic and metastatic capacity of cholangiocarcinoma and reveals the probable underlying mechanisms. PMID:24169343

Safety Considerations in the Use of Ketorolac for Postoperative Pain.

PubMed

Maslin, Benjamin; Lipana, Lawrence; Roth, Brandon; Kodumudi, Gopal; Vadivelu, Nalini

2017-01-01

Ketorolac use has significantly expanded for postoperative pain management since it first became available in the United States, primarily due to well established effects on patient pain scores and its ability to reduce perioperative opioid requirements. As an inhibitor of cyclooxygenase, ketorolac use has raised clinical concern including particular controversy regarding its potential effects on bone healing, postoperative kidney function and perioperative bleeding. To review the supporting data from clinical studies addressing the safety of ketorolac use for postoperative pain. This review highlights the most up-to-date research from clinical trials as well as from retrospective studies and meta-analyses regarding the effects of perioperative use of ketorolac on bone healing, kidney function and blood loss. Based on the most up-to-date literature, ketorolac in normal doses has been demonstrated to be safe with respect to bone healing. In patients with normal kidney function, numerous studies have established the safety of Ketorolac; however other studies have raised safety concerns in patients with comorbid kidney, heart and liver disease. While there is evidence that ketorolac may cause prolonged bleeding time and may be associated with increased postoperative blood loss after tonsillectomy, large scale prospective randomized controlled trials and subsequent meta-analyses have failed to establish an association of ketorolac use and perioperative blood loss. Perioperative administration of ketorolac has been demonstrated to be safe and effective in healthy patients and is particularly beneficial as an opioid-sparing agent in vulnerable patient groups. However, in certain surgical and medical contexts, proper patient selection based on the multidisciplinary collaboration between perioperative clinician specialists will optimize patient safety and pain management outcomes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Processing data communications events by awakening threads in parallel active messaging interface of a parallel computer

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

Archer, Charles J.; Blocksome, Michael A.; Ratterman, Joseph D.

Processing data communications events in a parallel active messaging interface (`PAMI`) of a parallel computer that includes compute nodes that execute a parallel application, with the PAMI including data communications endpoints, and the endpoints are coupled for data communications through the PAMI and through other data communications resources, including determining by an advance function that there are no actionable data communications events pending for its context, placing by the advance function its thread of execution into a wait state, waiting for a subsequent data communications event for the context; responsive to occurrence of a subsequent data communications event for themore » context, awakening by the thread from the wait state; and processing by the advance function the subsequent data communications event now pending for the context.« less

Nuclear masses far from stability: the interplay of theory and experiment

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

Haustein, P.E.

1985-01-01

Mass models seek, by a variety of theoretical approaches, to reproduce the measured mass surface and to predict unmeasured masses beyond it. Subsequent measurements of these predicted nuclear masses permit an assessment of the quality of the mass predictions from the various models. Since the last comprehensive revision of the mass predictions (in the mid-to-late 1970's) over 300 new masses have been reported. Global analyses of these data have been performed by several numerical and graphical methods. These have identified both the strengths and weaknesses of the models. In some cases failures in individual models are distinctly apparent when themore » new mass data are plotted as functions of one or more selected physical parameters. Several examples will be given. Future theoretical efforts will also be discussed.« less

Oxidation of cefazolin by potassium permanganate: Transformation products and plausible pathways.

PubMed

Li, Liping; Wei, Dongbin; Wei, Guohua; Du, Yuguo

2016-04-01

Cefazolin was demonstrated to exert high reactivity toward permanganate (Mn(VII)), a common oxidant in water pre-oxidation treatment. In this study, five transformation products were found to be classified into three categories according to the contained characteristic functional groups: three (di-)sulfoxide products, one sulfone product and one di-ketone product. Products analyses showed that two kinds of reactions including oxidation of thioether and the cleavage of unsaturated CC double bond occurred during transformation of cefazolin by Mn(VII). Subsequently, the plausible transformation pathways under different pH conditions were proposed based on the identified products and chemical reaction principles. More importantly, the simulation with real surface water matrix indicated that the proposed transformation pathways of cefazolin could be replayed in real water treatment practices. Copyright © 2016 Elsevier Ltd. All rights reserved.

Solid-to-solid phase transformations of nanostructured selenium-tin thin films induced by thermal annealing in oxygen atmosphere

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

Serra, A.; Rossi, M.; Buccolieri, A.

2014-06-19

The structural and morphological evolution of nanostructured thin films obtained from thermal evaporation of polycrystalline Sn-Se starting charge as a function of the subsequent annealing temperature in an oxygen flow has been analysed. High-resolution transmission electron microscopy, small area electron diffraction, digital image processing, x-ray diffraction and Raman spectroscopy have been employed in order to investigate the structure and the morphology of the obtained films. The results evidenced, in the temperature range from RT to 500°C, the transition of the material from a homogeneous mixture of SnSe and SnSe{sub 2} nanocrystals, towards a homogeneous mixture of SnO{sub 2} and SeO{submore » 2} nanocrystals, with an intermediate stage in which only SnSe{sub 2} nanocrystals are present.« less

Social and economic conditions in childhood and the progression of functional health problems from midlife into old age

PubMed Central

Agahi, Neda; Shaw, Benjamin A; Fors, Stefan

2014-01-01

Background Childhood living conditions have been found to predict health and mortality in midlife and in old age. This study examines the associations between social and economic childhood conditions and the onset and progression of functional health problems from midlife into old age, and the extent to which potential associations are mediated by educational attainment and smoking. Methods Data from the Level of Living Survey and the Swedish Panel Study of Living Conditions of the Oldest Old were merged to create a longitudinal data set with five repeated measures from 1968 to 2004 (n=1765, aged 30–50 years and free from functional health problems at baseline). Multilevel regression models were used to analyse retrospective reports of social and economic conditions in childhood (eg, conflicts or economic problems in the family) in relation to the progression of functional health problems over the 36-year period. Results Results showed that social and economic disadvantages in childhood were associated with an earlier onset and a faster progression of functional health problems from midlife into old age. Subsequent models showed that differences in educational attainment, but not smoking, explained much of the association between childhood disadvantages and trajectories of functional health problems. Conclusions According to these results, adverse social and economic conditions in childhood affect the development of functional health problems from midlife into old age indirectly through less favourable life careers, including lower education. Creating equal opportunities for educational attainment may help reduce the long-term effects of disadvantaged childhood conditions and postpone functional health problems. PMID:24759781

Personal care services provided to children with special health care needs (CSHCN) and their subsequent use of physician services.

PubMed

Miller, Thomas R; Elliott, Timothy R; McMaughan, Darcy M; Patnaik, Ashweeta; Naiser, Emily; Dyer, James A; Fournier, Constance J; Hawes, Catherine; Phillips, Charles D

2013-10-01

Medicaid Personal Care Services (PCS) help families meet children's needs for assistance with functional tasks. However, PCS may have other effects on a child's well-being, but research has not yet established the existence of such effects. To investigate the relationship between the number of PCS hours a child receives with subsequent visits to physicians for evaluation and management (E&M) services. Assessment data for 2058 CSHCN receiving PCS were collected in 2008 and 2009. Assessment data were matched with Medicaid claims data for the period of 1 year after the assessment. Zero-inflated negative binomial and generalized linear multivariate regression models were used in the analyses. These models included patient demographics, health status, household resources, and use of other medical services. For every 10 additional PCS hours authorized for a child, the odds of having an E&M physician visit in the next year were reduced by 25%. However, the number of PCS hours did not have a significant effect on the number of visits by those children who did have a subsequent E&M visit. A variety of demographic and health status measures also affect physician use. Medicaid PCS for CSHCN may be associated with reduced physician usage because of benefits realized by continuity of care, the early identification of potential health threats, or family and patient education. PCS services may contribute to a child's well-being by providing continuous relationships with the care team that promote good chronic disease management, education, and support for the family. Copyright © 2013 Elsevier Inc. All rights reserved.

Equilibrium, quasi-equilibrium, and nonequilibrium freezing of mammalian embryos.

PubMed

Mazur, P

1990-08-01

The first successful freezing of early embryos to -196 degrees C in 1972 required that they be cooled slowly at approximately 1 degree C/min to about -70 degrees C. Subsequent observations and physical/chemical analyses indicate that embryos cooled at that rate dehydrate sufficiently to maintain the chemical potential of their intracellular water close to that of the water in the partly frozen extracellular solution. Consequently, such slow freezing is referred to as equilibrium freezing. In 1972 and since, a number of investigators have studied the responses of embryos to departures from equilibrium freezing. When disequilibrium is achieved by the use of higher constant cooling rates to -70 degrees C, the results is usually intracellular ice formation and embryo death. That result is quantitatively in accord with the predictions of the physical/chemical analysis of the kinetics of water loss as a function of cooling rate. However, other procedures involving rapid nonequilibrium cooling do not result in high mortality. One common element in these other nonequilibrium procedures is that, before the temperature has dropped to a level that permits intracellular ice formation, the embryo water content is reduced to the point at which the subsequent rapid nonequilibrium cooling results in either the formation of small innocuous intracellular ice crystals or the conversion of the intracellular solution into a glass. In both cases, high survival requires that subsequent warming be rapid, to prevent recrystallization or devitrification. The physical/chemical analysis developed for initially nondehydrated cells appears generally applicable to these other nonequilibrium procedures as well.

Disrupted resting-state functional architecture of the brain after 45-day simulated microgravity

PubMed Central

Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

2014-01-01

Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of −6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of −6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of −6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity. PMID:24926242

Energyscapes and prey fields shape a North Atlantic seabird wintering hotspot under climate change

PubMed Central

Fort, J.; Mathewson, P. D.; Speirs, D. C.; Perret, S.; Porter, W. P.; Wilson, R. J.

2018-01-01

There is an urgent need for a better understanding of animal migratory ecology under the influence of climate change. Most current analyses require long-term monitoring of populations on the move, and shorter-term approaches are needed. Here, we analysed the ecological drivers of seabird migration within the framework of the energyscape concept, which we defined as the variations in the energy requirements of an organism across geographical space as a function of environmental conditions. We compared the winter location of seabirds with their modelled energy requirements and prey fields throughout the North Atlantic. Across six winters, we tracked the migration of 94 little auks (Alle alle), a key sentinel Arctic species, between their East Greenland breeding site and wintering areas off Newfoundland. Winter energyscapes were modelled with Niche Mapper™, a mechanistic tool which takes into account local climate and bird ecophysiology. Subsequently, we used a resource selection function to explain seabird distributions through modelled energyscapes and winter surface distribution of one of their main prey, Calanus finmarchicus. Finally, future energyscapes were calculated according to IPCC climate change scenarios. We found that little auks targeted areas with high prey densities and moderately elevated energyscapes. Predicted energyscapes for 2050 and 2095 showed a decrease in winter energy requirements under the high emission scenario, which may be beneficial if prey availability is maintained. Overall, our study demonstrates the great potential of the energyscape concept for the study of animal spatial ecology, in particular in the context of global change. PMID:29410875

A novel mutation in TFL1 homolog affecting determinacy in cowpea (Vigna unguiculata).

PubMed

Dhanasekar, P; Reddy, K S

2015-02-01

Mutations in the widely conserved Arabidopsis Terminal Flower 1 (TFL1) gene and its homologs have been demonstrated to result in determinacy across genera, the knowledge of which is lacking in cowpea. Understanding the molecular events leading to determinacy of apical meristems could hasten development of cowpea varieties with suitable ideotypes. Isolation and characterization of a novel mutation in cowpea TFL1 homolog (VuTFL1) affecting determinacy is reported here for the first time. Cowpea TFL1 homolog was amplified using primers designed based on conserved sequences in related genera and sequence variation was analysed in three gamma ray-induced determinate mutants, their indeterminate parent "EC394763" and two indeterminate varieties. The analyses of sequence variation exposed a novel SNP distinguishing the determinate mutants from the indeterminate types. The non-synonymous point mutation in exon 4 at position 1,176 resulted from transversion of cytosine (C) to adenine (A) leading to an amino acid change (Pro-136 to His) in determinate mutants. The effect of the mutation on protein function and stability was predicted to be detrimental using different bioinformatics/computational tools. The functionally significant novel substitution mutation is hypothesized to affect determinacy in the cowpea mutants. Development of suitable regeneration protocols in this hitherto recalcitrant crop and subsequent complementation assay in mutants or over-expressing assay in parents could decisively conclude the role of the SNP in regulating determinacy in these cowpea mutants.

A Rare SNP Identified a TCP Transcription Factor Essential for Tendril Development in Cucumber.

PubMed

Wang, Shenhao; Yang, Xueyong; Xu, Mengnan; Lin, Xingzhong; Lin, Tao; Qi, Jianjian; Shao, Guangjin; Tian, Nana; Yang, Qing; Zhang, Zhonghua; Huang, Sanwen

2015-12-07

Rare genetic variants are abundant in genomes but less tractable in genome-wide association study. Here we exploit a strategy of rare variation mapping to discover a gene essential for tendril development in cucumber (Cucumis sativus L.). In a collection of >3000 lines, we discovered a unique tendril-less line that forms branches instead of tendrils and, therefore, loses its climbing ability. We hypothesized that this unusual phenotype was caused by a rare variation and subsequently identified the causative single nucleotide polymorphism. The affected gene TEN encodes a TCP transcription factor conserved within the cucurbits and is expressed specifically in tendrils, representing a new organ identity gene. The variation occurs within a protein motif unique to the cucurbits and impairs its function as a transcriptional activator. Analyses of transcriptomes from near-isogenic lines identified downstream genes required for the tendril's capability to sense and climb a support. This study provides an example to explore rare functional variants in plant genomes. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Right vs. left sensorimotor cortex suction-ablation in the rat: no difference in beam-walking recovery.

PubMed

Goldstein, L B

1995-03-13

The ability of rats to traverse a narrow elevated beam has been used to quantitate recovery of hindlimb motor function after unilateral injury to the sensorimotor cortex. We tested the hypothesis that the rate of spontaneous beam-walking recovery varies with the side of the cortex lesion. Groups of rats that were trained at the beam-walking task underwent suction-ablation of either the right or left hindlimb sensorimotor cortex. There was no difference in hindlimb motor function between the groups on the first post-operative beam-waking trial carried out the day after cortex ablation and no difference between the groups in overall recovery rates over the next two weeks. Subsequent analyses of lesion surface parameters showed no differences in lesion size or extent. Regardless of the side of the lesion, there were also no differences between the right and left hemispheres in norepinephrine content of the lesioned or contralateral cortex. We conclude that the side of sensorimotor cortex ablation injury does not differentially affect the rate of spontaneous motor recovery as measured with the beam-walking task.

Mapping the temperature-dependent conformational landscapes of the dynamic enzymes cyclophilin A and urease

NASA Astrophysics Data System (ADS)

Thorne, Robert; Keedy, Daniel; Warkentin, Matthew; Fraser, James; Moreau, David; Atakisi, Hakan; Rau, Peter

Proteins populate complex, temperature-dependent ensembles of conformations that enable their function. Yet in X-ray crystallographic studies, roughly 98% of structures have been determined at 100 K, and most refined to only a single conformation. A combination of experimental methods enabled by studies of ice formation and computational methods for mining low-density features in electron density maps have been applied to determine the evolution of the conformational landscapes of the enzymes cyclophilin A and urease between 300 K and 100 K. Minority conformations of most side chains depopulate on cooling from 300 to ~200 K, below which subsequent conformational evolution is quenched. The characteristic temperatures for this depopulation are highly heterogeneous throughout each enzyme. The temperature-dependent ensemble of the active site flap in urease has also been mapped. These all-atom, site-resolved measurements and analyses rule out one interpretation of the protein-solvent glass transition, and give an alternative interpretation of a dynamical transition identified in site-averaged experiments. They demonstrate a powerful approach to structural characterization of the dynamic underpinnings of protein function. Supported by NSF MCB-1330685.

A role for the CXCR4-CXCL12 axis in the little skate, Leucoraja erinacea.

PubMed

Hersh, Taylor A; Dimond, Alexandria L; Ruth, Brittany A; Lupica, Noah V; Bruce, Jacob C; Kelley, John M; King, Benjamin L; Lutton, Bram V

2018-04-11

The interaction between C-X-C chemokine receptor type 4 (CXCR4) and its cognate ligand, C-X-C motif chemokine ligand 12 (CXCL12), plays a critical role in regulating hematopoietic stem cell activation and subsequent cellular mobilization. Extensive studies of these genes have been conducted in mammals, but much less is known about the expression and function of CXCR4 and CXCL12 in non-mammalian vertebrates. In the present study, we identify simultaneous expression of CXCR4 and CXCL12 orthologues in the epigonal organ (the primary hematopoietic tissue) of the little skate, Leucoraja erinacea. Genetic and phylogenetic analyses were functionally supported by significant mobilization of leukocytes following administration of Plerixafor: a CXCR4 antagonist and clinically important drug. Our results provide evidence that, as in humans, Plerixafor disrupts CXCR4/CXCL12 binding in the little skate, facilitating release of leukocytes into the bloodstream. Our study illustrates the value of the little skate as a model organism, particularly in studies of hematopoiesis, and potentially for pre-clinical research on hematological and vascular disorders.

Periodontal regeneration via chemo-attractive constructs.

PubMed

Cai, Xinjie; Yang, Fang; Walboomers, X Frank; Wang, Yining; Jansen, John A; van den Beucken, Jeroen J J P; Plachokova, Adelina S

2018-05-19

Chemo-attractants, such as stromal cell-derived factor-1α (SDF-1α), can offer an advantage for periodontal regeneration by recruiting the patient's own stem cells to stimulate self-repair. We here developed a chemo-attractive construct for periodontal regeneration using SDF-1α and evaluated its efficacy in vivo. SDF-1α was loaded on gelatin sponge and tested in vitro for SDF-1α release. Subsequently, SDF-1α constructs were implanted into rat periodontal defects for 1 and 6 weeks, with unloaded materials and empty defects as controls. The regenerative efficacy was evaluated by micro-CT, histological and histomorphometrical analyses. In vitro results showed limited SDF-1α release up to 35 days. In contrast, SDF-1α constructs significantly improved periodontal defect regeneration in terms of alveolar bone height, new bone area, and functional ligament length. Additionally, SDF-1α constructs decreased the inflammatory response at week 6. Chemo-attractive constructs significantly improved periodontal regeneration in terms of alveolar bone height, new bone area, and functional ligament length. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Microdissection of Black Widow Spider Silk-producing Glands

PubMed Central

Hsia, Yang; Gnesa, Eric; Zhao, Liang; Franz, Andreas; Vierra, Craig

2011-01-01

Modern spiders spin high-performance silk fibers with a broad range of biological functions, including locomotion, prey capture and protection of developing offspring 1,2. Spiders accomplish these tasks by spinning several distinct fiber types that have diverse mechanical properties. Such specialization of fiber types has occurred through the evolution of different silk-producing glands, which function as small biofactories. These biofactories manufacture and store large quantities of silk proteins for fiber production. Through a complex series of biochemical events, these silk proteins are converted from a liquid into a solid material upon extrusion. Mechanical studies have demonstrated that spider silks are stronger than high-tensile steel 3. Analyses to understand the relationship between the structure and function of spider silk threads have revealed that spider silk consists largely of proteins, or fibroins, that have block repeats within their protein sequences 4. Common molecular signatures that contribute to the incredible tensile strength and extensibility of spider silks are being unraveled through the analyses of translated silk cDNAs. Given the extraordinary material properties of spider silks, research labs across the globe are racing to understand and mimic the spinning process to produce synthetic silk fibers for commercial, military and industrial applications. One of the main challenges to spinning artificial spider silk in the research lab involves a complete understanding of the biochemical processes that occur during extrusion of the fibers from the silk-producing glands. Here we present a method for the isolation of the seven different silk-producing glands from the cobweaving black widow spider, which includes the major and minor ampullate glands [manufactures dragline and scaffolding silk] 5,6, tubuliform [synthesizes egg case silk] 7,8, flagelliform [unknown function in cob-weavers], aggregate [makes glue silk], aciniform [synthesizes prey wrapping and egg case threads] 9 and pyriform [produces attachment disc silk] 10. This approach is based upon anesthetizing the spider with carbon dioxide gas, subsequent separation of the cephalothorax from the abdomen, and microdissection of the abdomen to obtain the silk-producing glands. Following the separation of the different silk-producing glands, these tissues can be used to retrieve different macromolecules for distinct biochemical analyses, including quantitative real-time PCR, northern- and western blotting, mass spectrometry (MS or MS/MS) analyses to identify new silk protein sequences, search for proteins that participate in the silk assembly pathway, or use the intact tissue for cell culture or histological experiments. PMID:21248709

BACOM2.0 facilitates absolute normalization and quantification of somatic copy number alterations in heterogeneous tumor

NASA Astrophysics Data System (ADS)

Fu, Yi; Yu, Guoqiang; Levine, Douglas A.; Wang, Niya; Shih, Ie-Ming; Zhang, Zhen; Clarke, Robert; Wang, Yue

2015-09-01

Most published copy number datasets on solid tumors were obtained from specimens comprised of mixed cell populations, for which the varying tumor-stroma proportions are unknown or unreported. The inability to correct for signal mixing represents a major limitation on the use of these datasets for subsequent analyses, such as discerning deletion types or detecting driver aberrations. We describe the BACOM2.0 method with enhanced accuracy and functionality to normalize copy number signals, detect deletion types, estimate tumor purity, quantify true copy numbers, and calculate average-ploidy value. While BACOM has been validated and used with promising results, subsequent BACOM analysis of the TCGA ovarian cancer dataset found that the estimated average tumor purity was lower than expected. In this report, we first show that this lowered estimate of tumor purity is the combined result of imprecise signal normalization and parameter estimation. Then, we describe effective allele-specific absolute normalization and quantification methods that can enhance BACOM applications in many biological contexts while in the presence of various confounders. Finally, we discuss the advantages of BACOM in relation to alternative approaches. Here we detail this revised computational approach, BACOM2.0, and validate its performance in real and simulated datasets.

The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

PubMed Central

Dingemans, Jozef; Poudyal, Bandita

2018-01-01

ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two distinct pathways leading to biofilm formation and biofilm drug tolerance are under the control of two sets of amino acid residues located within the HmsP sensory domain of SagS. The respective amino acids are likely part of ligand binding interaction sites. Thus, our findings have the potential not only to enable the manipulation of SagS function but also to enable research of biofilm drug tolerance in a manner independent of biofilm formation (and vice versa). Moreover, the manipulation of SagS function represents a promising target/avenue open for biofilm control. PMID:29848761

Biological Communities in Desert Varnish and Potential Implications for Varnish Formation Mechanisms

NASA Astrophysics Data System (ADS)

Lang-Yona, Naama; Maier, Stefanie; Macholdt, Dorothea; Rodriguez-Caballero, Emilio; Müller-Germann, Isabell; Yordanova, Petya; Jochum, Klaus-Peter; Andreae, Meinrat O.; Pöschl, Ulrich; Weber, Bettina; Fröhlich-Nowoisky, Janine

2017-04-01

Desert varnishes are thin, orange to black coatings found on rocks in arid and semi-arid environments on Earth. The formation mechanisms of rock varnish are still under debate and the involvement of microorganisms in this process remains unclear. In this work we aimed to identify the microbial community occurring in rock varnish to potentially gain insights into the varnish formation mechanism. For this purpose, rocks coated with desert varnish were collected from the Anza-Borrego Desert, California, USA, as well as soils from underneath the rocks. DNA from both varnish coatings and soil samples was extracted and subsequently used for metagenomic analysis, as well as for q-PCR analyses for specific species quantification. The element composition of the varnish coatings was analyzed and compared to the soil samples. Rock varnish shows similar depleted elements, compared to soil, but Mn and Pb are 50-60 times enriched compared to the soil samples, and about 100 times enriched compared to the upper continental crust. Our genomic analyses suggest unique populations and different protein functional groups occurring in the varnish compared to soil samples. We discuss these differences and try to shed light on the mechanism of Mn oxyhydroxide production in desert varnish formation.

Residency hospital type and career paths in Japan: an analysis of physician registration cohorts.

PubMed

Koike, Soichi; Kodama, Tomoko; Matsumoto, Shinya; Ide, Hiroo; Yasunaga, Hideo; Imamura, Tomoaki

2010-01-01

In 2004, a new postgraduate medical training system was introduced in Japan and a shift of new graduates from university hospitals to other postgraduate education hospitals happened. The aim of this study is to analyse the past trends on postgraduate medical education choices and subsequent career options to discuss possible outcomes of the current shift and policy implications. Data from the national physician survey from 1976 to 2006 were analysed. The proportion change of physicians started their career in university hospitals was calculated. The career paths for physicians by different residency type were presented. More than 90% of physicians experienced university hospital work at least once in their 20-year careers. In their first 10 years of their career, physicians who started their residency in a university hospital tended to spend more years working in university hospitals, and those who started in other post-graduate training hospitals tended to spend less in university hospitals. Then, these groups presented quite similar patterns in their career choices. University hospitals need to strengthen their function as continuing education and career development centres and to adopt a less paternalistic approach, as fewer residents start their career in university hospitals.

Network Analysis Reveals Ecological Links between N-Fixing Bacteria and Wood-Decaying Fungi

PubMed Central

Hoppe, Björn; Kahl, Tiemo; Karasch, Peter; Wubet, Tesfaye; Bauhus, Jürgen; Buscot, François; Krüger, Dirk

2014-01-01

Nitrogen availability in dead wood is highly restricted and associations with N-fixing bacteria are thought to enable wood-decaying fungi to meet their nitrogen requirements for vegetative and generative growth. We assessed the diversity of nifH (dinitrogenase reductase) genes in dead wood of the common temperate tree species Fagus sylvatica and Picea abies from differently managed forest plots in Germany using molecular tools. By incorporating these genes into a large compilation of published nifH sequences and subsequent phylogenetic analyses of deduced proteins we verified the presence of diverse pools corresponding to functional nifH, almost all of which are new to science. The distribution of nifH genes strongly correlated with tree species and decay class, but not with forest management, while higher fungal fructification was correlated with decreasing nitrogen content of the dead wood and positively correlated with nifH diversity, especially during the intermediate stage of wood decay. Network analyses based on non-random species co-occurrence patterns revealed interactions among fungi and N-fixing bacteria in the dead wood and strongly indicate the occurrence of at least commensal relationships between these taxa. PMID:24505405

Network analysis reveals ecological links between N-fixing bacteria and wood-decaying fungi.

PubMed

Hoppe, Björn; Kahl, Tiemo; Karasch, Peter; Wubet, Tesfaye; Bauhus, Jürgen; Buscot, François; Krüger, Dirk

2014-01-01

Nitrogen availability in dead wood is highly restricted and associations with N-fixing bacteria are thought to enable wood-decaying fungi to meet their nitrogen requirements for vegetative and generative growth. We assessed the diversity of nifH (dinitrogenase reductase) genes in dead wood of the common temperate tree species Fagus sylvatica and Picea abies from differently managed forest plots in Germany using molecular tools. By incorporating these genes into a large compilation of published nifH sequences and subsequent phylogenetic analyses of deduced proteins we verified the presence of diverse pools corresponding to functional nifH, almost all of which are new to science. The distribution of nifH genes strongly correlated with tree species and decay class, but not with forest management, while higher fungal fructification was correlated with decreasing nitrogen content of the dead wood and positively correlated with nifH diversity, especially during the intermediate stage of wood decay. Network analyses based on non-random species co-occurrence patterns revealed interactions among fungi and N-fixing bacteria in the dead wood and strongly indicate the occurrence of at least commensal relationships between these taxa.

Integrated analysis of large space systems

NASA Technical Reports Server (NTRS)

Young, J. P.

1980-01-01

Based on the belief that actual flight hardware development of large space systems will necessitate a formalized method of integrating the various engineering discipline analyses, an efficient highly user oriented software system capable of performing interdisciplinary design analyses with tolerable solution turnaround time is planned Specific analysis capability goals were set forth with initial emphasis given to sequential and quasi-static thermal/structural analysis and fully coupled structural/control system analysis. Subsequently, the IAC would be expanded to include a fully coupled thermal/structural/control system, electromagnetic radiation, and optical performance analyses.

IPAC-Inlet Performance Analysis Code

NASA Technical Reports Server (NTRS)

Barnhart, Paul J.

1997-01-01

A series of analyses have been developed which permit the calculation of the performance of common inlet designs. The methods presented are useful for determining the inlet weight flows, total pressure recovery, and aerodynamic drag coefficients for given inlet geometric designs. Limited geometric input data is required to use this inlet performance prediction methodology. The analyses presented here may also be used to perform inlet preliminary design studies. The calculated inlet performance parameters may be used in subsequent engine cycle analyses or installed engine performance calculations for existing uninstalled engine data.

Use of a Chamber to Comprehensively Characterise Emissions and Subsequent Processes from a Light-Duty Diesel Engine

NASA Astrophysics Data System (ADS)

Allan, J. D.; Alfarra, M. R. R.; Whitehead, J.; McFiggans, G.; Kong, S.; Harrison, R. M.; Alam, M. S.; Hamilton, J. F.; Pereira, K. L.; Holmes, R. E.

2014-12-01

Around 1 in 3 light duty vehicles in the UK use diesel engines, meaning that on-road emissions of particulates, NOx and VOCs and subsequent chemical processes are substantially different to countries where gasoline engines dominate. As part of the Natural Environment Research Council (NERC) Com-Part project, emissions from a diesel engine dynamometer rig representative of the EURO 4 standard were studied. The exhaust was passed to the Manchester aerosol chamber, which consists of an 18 m3 teflon bag and by injecting a sample of exhaust fumes into filtered and chemically scrubbed air, a controllable dilution can be performed and the sample held in situ for analysis by a suite of instruments. The system also allows the injection of other chemicals (e.g. ozone, additional VOCs) and the initiation of photochemistry using a bank of halogen bulbs and a filtered Xe arc lamp to simulate solar light. Because a large volume of dilute emissions can be held for a period of hours, this permits a wide range of instrumentation to be used and relatively slow processes studied. Furthermore, because the bag is collapsible, the entire particulate contents can be collected on a filter for offline analysis. Aerosol microphysical properties are studied using a Scanning Mobility Particle Sizer (SMPS) and Centrifugal Particle Mass Analyser (CPMA); aerosol composition using a Soot Particle Aerosol Mass Spectrometer (SP-AMS), Single Particle Soot Photometer (SP2), Sunset Laboratories OC EC analyser and offline gas- and high performance liquid chromatography (employing advanced mass spectrometry such as ion trap and fourier transform ion cyclotron resonance); VOCs using comprehensive 2D gas chromatography; aerosol optical properties using a Cavity Attenuated Phase Shift Single Scattering Albedo monitor (CAPS-PMSSA), 3 wavelength Photoacoustic Soot Spectrometer (PASS-3) and Multi Angle Absorption Photometer (MAAP); particle hygroscopcity using a Hygroscopicity Tandem Differential Mobility Analyser (HTDMA) and monodisperse Cloud Condensation Nuclei counter (CCN); and measurements of ozone, NOx and CO2. Here we present the first results, where we explored the trends as a function of engine speed, load, exhaust treatment (an oxidizing catalytic converter), dilution factor and exposure to light.

Functional Analyses and Treatment of Precursor Behavior

PubMed Central

Najdowski, Adel C; Wallace, Michele D; Ellsworth, Carrie L; MacAleese, Alicia N; Cleveland, Jackie M

2008-01-01

Functional analysis has been demonstrated to be an effective method to identify environmental variables that maintain problem behavior. However, there are cases when conducting functional analyses of severe problem behavior may be contraindicated. The current study applied functional analysis procedures to a class of behavior that preceded severe problem behavior (precursor behavior) and evaluated treatments based on the outcomes of the functional analyses of precursor behavior. Responding for all participants was differentiated during the functional analyses, and individualized treatments eliminated precursor behavior. These results suggest that functional analysis of precursor behavior may offer an alternative, indirect method to assess the operant function of severe problem behavior. PMID:18468282

Striatal functional connectivity changes following specific balance training in elderly people: MRI results of a randomized controlled pilot study.

PubMed

Magon, Stefano; Donath, Lars; Gaetano, Laura; Thoeni, Alain; Radue, Ernst-Wilhelm; Faude, Oliver; Sprenger, Till

2016-09-01

Practice-induced effects of specific balance training on brain structure and activity in elderly people are largely unknown. In the present study, we investigated morphological and functional brain changes following slacking training (balancing over nylon ribbons) in a group of elderly people. Twenty-eight healthy volunteers were recruited and randomly assigned to the intervention (mean age: 62.3±5.4years) or control group (mean age: 61.8±5.3years). The intervention group completed six-weeks of slackline training. Brain morphological changes were investigated using voxel-based morphometry and functional connectivity changes were computed via independent component analysis and seed-based analyses. All analyses were applied to the whole sample and to a subgroup of participants who improved in slackline performance. The repeated measures analysis of variance showed a significant interaction effect between groups and sessions. Specifically, the Tukey post-hoc analysis revealed a significantly improved slackline standing performance after training for the left leg stance time (pre: 4.5±3.6s vs. 26.0±30.0s, p<0.038) as well as for tandem stance time (pre: 1.4±0.6s vs. post: 4.5±4.0s, p=0.003) in the intervention group. No significant changes in balance performance were observed in the control group. The MRI analysis did not reveal morphological or functional connectivity differences before or after the training between the intervention and control groups (whole sample). However, subsequent analysis in subjects with improved slackline performance showed a decrease of connectivity between the striatum and other brain areas during the training period. These preliminary results suggest that improved balance performance with slackline training goes along with an increased efficiency of the striatal network. Copyright © 2016 Elsevier B.V. All rights reserved.

Control of flowering time and cold response by a NAC-domain protein in Arabidopsis.

PubMed

Yoo, So Yeon; Kim, Yunhee; Kim, Soo Young; Lee, Jong Seob; Ahn, Ji Hoon

2007-07-25

Plants must integrate complex signals from environmental and endogenous cues to fine-tune the timing of flowering. Low temperature is one of the most common environmental stresses that affect flowering time; however, molecular mechanisms underlying the cold temperature regulation of flowering time are not fully understood. We report the identification of a novel regulator, LONG VEGETATIVE PHASE 1 (LOV1), that controls flowering time and cold response. An Arabidopsis mutant, longvegetative phase 1-1D (lov1-1D) showing the late-flowering phenotype, was isolated by activation tagging screening. Subsequent analyses demonstrated that the phenotype of the mutant resulted from the overexpression of a NAC-domain protein gene (At2g02450). Both gain- and loss-of-function alleles of LOV1 affected flowering time predominantly under long-day but not short-day conditions, suggesting that LOV1 may act within the photoperiod pathway. The expression of CONSTANS (CO), a floral promoter, was affected by LOV1 level, suggesting that LOV1 controls flowering time by negatively regulating CO expression. The epistatic relationship between CO and LOV1 was consistent with this proposed regulatory pathway. Physiological analyses to elucidate upstream signalling pathways revealed that LOV1 regulates the cold response in plants. Loss of LOV1 function resulted in hypersensitivity to cold temperature, whereas a gain-of-function allele conferred cold tolerance. The freezing tolerance was accompanied by upregulation of cold response genes, COLD-REGULATED 15A (COR15A) and COLD INDUCED 1 (KIN1) without affecting expression of the C-repeat-binding factor/dehydration responsive element-binding factor 1 (CBF/DREB1) family of genes. Our study shows that LOV1 functions as a floral repressor that negatively regulates CO expression under long-day conditions and acts as a common regulator of two intersecting pathways that regulate flowering time and the cold response, respectively. Our results suggest an overlapping pathway for controlling cold stress response and flowering time in plants.

A left cerebellar pathway mediates language in prematurely-born young adults

PubMed Central

Constable, R. Todd; Vohr, Betty R.; Scheinost, Dustin; Benjamin, Jennifer R.; Fulbright, Robert K.; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Zhang, Heping; Papademetris, Xenophon; Ment, Laura R.

2012-01-01

Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20 years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain. PMID:22982585

Thoracic Kyphosis and Physical Function: The Framingham Study.

PubMed

Lorbergs, Amanda L; Murabito, Joanne M; Jarraya, Mohamed; Guermazi, Ali; Allaire, Brett T; Yang, Laiji; Kiel, Douglas P; Cupples, L Adrienne; Bouxsein, Mary L; Travison, Thomas G; Samelson, Elizabeth J

2017-10-01

To evaluate the association between thoracic kyphosis and physical function. Prospective cohort. Framingham, Massachusetts. Framingham Heart Study Offspring and Third Generation cohort members who had computed tomography (CT) performed between 2002 and 2005 and physical function assessed a mean 3.4 years later (N = 1,100; mean age 61 ± 8, range 50-85). Thoracic kyphosis (Cobb angle, T4-T12) was measured in degrees using supine CT scout images. Participants were categorized according to Cobb angle to compare those in the highest quartile (Q4, most-severe kyphosis) with those in the lowest quartiles (Q1-Q3). Quick walking speed (m/s), chair-stand time (seconds), grip strength (kg), and self-reported impairments were assessed using standardized procedures. Analyses were adjusted for age, height, weight, smoking, follow-up time, vertebral fractures, and prevalent spinal degeneration. Thoracic kyphosis was not associated with physical function in women or men, and these results were consistent in those younger than 65 and those aged 65 and older. For example, walking speed was similar in adults younger than 65 with and without severe kyphosis (women, Q4: 1.38 m/s, Q1-Q3: 1.40 m/s, P = .69; men, Q4: 1.65 m/s, Q1-Q3: 1.60 m/s; P = .39). In healthy relatively high-functioning women and men, kyphosis severity was not associated with subsequent physical function. Individuals at risk of functional decline cannot be targeted based on supine CT thoracic curvature measures alone. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Motor Function Is Associated With Incident Disability in Older African Americans

PubMed Central

Wilson, Robert S.; Yu, Lei; Boyle, Patricia A.; Bennett, David A.; Barnes, Lisa L.

2016-01-01

Background: Disability in older African American adults is common, but its basis is unclear. We tested the hypothesis that the level of motor function is associated with incident disability in older African Americans after adjusting for cognition. Methods: A prospective observational cohort study of 605 older community-dwelling African American adults without dementia was carried out. Baseline global motor score summarized 11 motor performances, cognition was based on 19 cognitive tests, and self-reported disability was obtained annually. We examined the association of motor function with incident disability (instrumental activities of daily living [IADL], activities of daily living [ADL], and mobility disability) with a series of Cox proportional hazards models which controlled for age, sex, and education. Results: Average follow-up was about 5 years. In proportional hazards models, a 1-SD increase in baseline level of global motor score was associated with about a 50% decrease in the risk of subsequent IADL, ADL, and mobility disability (all p values < .001). These associations were unchanged in analyses controlling for cognition and other covariates. Further, the association of global motor score and incident ADL disability varied with the level of cognition (estimate −5.541, SE 1.634, p < .001), such that higher motor function was more protective at higher levels of cognition. Mobility and dexterity components of global motor score were more strongly associated with incident disability than strength (all p values < .001). Conclusions: Better motor function in older African Americans is associated with a decreased risk of developing disability. Moreover, the association of motor function and disability is stronger in individuals with better cognitive function. PMID:26525087

Intrinsic brain abnormalities in young healthy adults with childhood trauma: A resting-state functional magnetic resonance imaging study of regional homogeneity and functional connectivity.

PubMed

Lu, Shaojia; Gao, Weijia; Wei, Zhaoguo; Wang, Dandan; Hu, Shaohua; Huang, Manli; Xu, Yi; Li, Lingjiang

2017-06-01

Childhood trauma confers great risk for the development of multiple psychiatric disorders; however, the neural basis for this association is still unknown. The present resting-state functional magnetic resonance imaging study aimed to detect the effects of childhood trauma on brain function in a group of young healthy adults. In total, 24 healthy individuals with childhood trauma and 24 age- and sex-matched adults without childhood trauma were recruited. Each participant underwent resting-state functional magnetic resonance imaging scanning. Intra-regional brain activity was evaluated by regional homogeneity method and compared between groups. Areas with altered regional homogeneity were further selected as seeds in subsequent functional connectivity analysis. Statistical analyses were performed by setting current depression and anxiety as covariates. Adults with childhood trauma showed decreased regional homogeneity in bilateral superior temporal gyrus and insula, and the right inferior parietal lobule, as well as increased regional homogeneity in the right cerebellum and left middle temporal gyrus. Regional homogeneity values in the left middle temporal gyrus, right insula and right cerebellum were correlated with childhood trauma severity. In addition, individuals with childhood trauma also exhibited altered default mode network, cerebellum-default mode network and insula-default mode network connectivity when the left middle temporal gyrus, right cerebellum and right insula were selected as seed area, respectively. The present outcomes suggest that childhood trauma is associated with disturbed intrinsic brain function, especially the default mode network, in adults even without psychiatric diagnoses, which may mediate the relationship between childhood trauma and psychiatric disorders in later life.

Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum.

PubMed

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-03-01

Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates ( N =124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked.

Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum

PubMed Central

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.; Koenigs, Michael

2016-01-01

Background Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. Methods We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates (N=124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Results Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. Conclusion These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked. PMID:28367514

Biomarkers of Risk for Post-Traumatic Stress Disorder (PTSD)

DTIC Science & Technology

2010-05-01

Price, L.H., Carpenter, L.L., Alberto Del Porto, J. Depression and stress: is there an endophenotype? Revista Brasileira de Psiquiatria, 29 (Supl...insufficient power, and the lack of inclusion of subsequent diagnoses as well as lifetime diagnoses in these analyses. Further analyses will include...partial or nonresponse to antidepressants. Journal of Clinical Psychiatry, 66, 1234- 8, 2005. 16. Carpenter, L.L, Schecter, J.M., Tyrka, A.R., Feijo de

The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity.

PubMed

Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C; Morgan, Todd E; Finch, Caleb E; Pike, Christian J; Mack, Wendy J; Cadenas, Enrique; Brinton, Roberta D

2015-07-01

The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the present study determined genomic, biochemical, brain metabolic, and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in fluorodeoxyglucose-positron emission tomography (FDG-PET) brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/insulin-like growth factor 1 and adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (AMPK/PGC1α) signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later-life vulnerability to hypometabolic conditions such as Alzheimer's. Copyright © 2015 Elsevier Inc. All rights reserved.

Contributions of volumetrics of the hippocampus and thalamus to verbal memory in temporal lobe epilepsy patients.

PubMed

Stewart, Christopher C; Griffith, H Randall; Okonkwo, Ozioma C; Martin, Roy C; Knowlton, Robert K; Richardson, Elizabeth J; Hermann, Bruce P; Seidenberg, Michael

2009-02-01

Recent theories have posited that the hippocampus and thalamus serve distinct, yet related, roles in episodic memory. Whereas the hippocampus has been implicated in long-term memory encoding and storage, the thalamus, as a whole, has been implicated in the selection of items for subsequent encoding and the use of retrieval strategies. However, dissociating the memory impairment that occurs following thalamic injury as distinguished from that following hippocampal injury has proven difficult. This study examined relationships between MRI volumetric measures of the hippocampus and thalamus and their contributions to prose and rote verbal memory functioning in 18 patients with intractable temporal lobe epilepsy (TLE). Results revealed that bilateral hippocampal and thalamic volume independently predicted delayed prose verbal memory functioning. However, bilateral hippocampal, but not thalamic, volume predicted delayed rote verbal memory functioning. Follow-up analyses indicated that bilateral thalamic volume independently predicted immediate prose, but not immediate rote, verbal recall, whereas bilateral hippocampal volume was not associated with any of these immediate memory measures. These findings underscore the cognitive significance of thalamic atrophy in chronic TLE, demonstrating that hippocampal and thalamic volume make quantitatively, and perhaps qualitatively, distinct contributions to episodic memory functioning in TLE patients. They are also consistent with theories proposing that the hippocampus supports long-term memory encoding and storage, whereas the thalamus is implicated in the executive aspects of episodic memory.

Gastric ulceration subsequent to partial invagination of the stomach in a dog with gastric dilatation-volvulus.

PubMed

Parton, Amanda T; Volk, Susan W; Weisse, Chick

2006-06-15

CASE DESCRIPTION-An 8-year-old castrated male German Shepherd Dog was evaluated because of abdominal distension, retching, and vomiting. CLINICAL FINDINGS-Gastric dilatation-volvulus was suspected on the basis of the dog's signalment, history, clinical signs, and results of clinicopathologic analyses and abdominal radiography. Celiotomy was performed, and gastric dilatation-volvulus was confirmed along with splenomegaly. Gastric invagination was performed over an area of gastric necrosis. The dog was reevaluated 21 days later after an episode of collapse. Findings of physical examination and clinicopathologic analyses were suggestive of internal hemorrhage. Abdominal ultrasonography and subsequent celiotomy revealed severe gastric ulceration at the gastric invagination site, splenic torsion, and a focal splenic infarct. TREATMENT AND OUTCOME-Splenectomy and gastrectomy of the necrotic tissue were performed. The dog was discharged from the hospital, and the owner was instructed to administer gastroprotectants and feed the dog a bland diet. The dog was reported to be healthy 3.25 years after surgery. CLINICAL RELEVANCE-Findings suggest that complications associated with the gastric invagination procedure include severe gastric ulceration that may require subsequent surgery. Prolonged treatment with gastroprotectants following gastric invagination surgery may be necessary to avoid gastric ulceration in dogs.

Marginal Utility of Conditional Sensitivity Analyses for Dynamic Models

EPA Science Inventory

Background/Question/MethodsDynamic ecological processes may be influenced by many factors. Simulation models thatmimic these processes often have complex implementations with many parameters. Sensitivityanalyses are subsequently used to identify critical parameters whose uncertai...

Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

PubMed

Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

2014-07-16

To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development.

PubMed

Covassin, L D; Siekmann, A F; Kacergis, M C; Laver, E; Moore, J C; Villefranc, J A; Weinstein, B M; Lawson, N D

2009-05-15

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development.

Altered emotion regulation capacity in social phobia as a function of comorbidity

PubMed Central

Craske, Michelle G.; Taylor, Shelley E.; Lieberman, Matthew D.

2015-01-01

Social phobia (SP) has been associated with amygdala hyperreactivity to fear-relevant stimuli. However, little is known about the neural basis of SP individuals’ capacity to downregulate their responses to such stimuli and how such regulation varies as a function of comorbid depression and anxiety. We completed an functional magnetic resonance imaging (fMRI) study wherein SP participants without comorbidity (n = 30), with comorbid depression (n = 18) and with comorbid anxiety (n = 19) and healthy controls (n = 15) were scanned while completing an affect labeling emotion regulation task. Individuals with SP as a whole exhibited a reversal of the pattern observed in healthy controls in that they showed upregulation of amygdala activity during affect labeling. However, subsequent analyses revealed a more complex picture based on comorbidity type. Although none of the SP subgroups showed the normative pattern of amygdala downregulation, it was those with comorbid depression specifically who showed significant upregulation. Effects could not be attributed to differences in task performance, amygdala reactivity or right ventral lateral prefrontal cortex (RVLPFC) engagement, but may stem from dysfunctional communication between amygdala and RVLPFC. Furthermore, the particularly altered emotion regulation seen in those with comorbid depression could not be fully explained by symptom severity or state anxiety. Results reveal altered emotion regulation in SP, especially when comorbid with depression. PMID:24813437

Control of nucleus accumbens activity with neurofeedback.

PubMed

Greer, Stephanie M; Trujillo, Andrew J; Glover, Gary H; Knutson, Brian

2014-08-01

The nucleus accumbens (NAcc) plays critical roles in healthy motivation and learning, as well as in psychiatric disorders (including schizophrenia and attention deficit hyperactivity disorder). Thus, techniques that confer control of NAcc activity might inspire new therapeutic interventions. By providing second-to-second temporal resolution of activity in small subcortical regions, functional magnetic resonance imaging (fMRI) can resolve online changes in NAcc activity, which can then be presented as "neurofeedback." In an fMRI-based neurofeedback experiment designed to elicit NAcc activity, we found that subjects could increase their own NAcc activity, and that display of neurofeedback significantly enhanced their ability to do so. Subjects were not as capable of decreasing their NAcc activity, however, and enhanced control did not persist after subsequent removal of neurofeedback. Further analyses suggested that individuals who recruited positive aroused affect were better able to increase NAcc activity in response to neurofeedback, and that NAcc neurofeedback also elicited functionally correlated activity in the medial prefrontal cortex. Together, these findings suggest that humans can modulate their own NAcc activity and that fMRI-based neurofeedback may augment their efforts. The observed association between positive arousal and effective NAcc control further supports an anticipatory affect account of NAcc function. Copyright © 2014 Elsevier Inc. All rights reserved.

Biotic and environmental stress induces nitration and changes in structure and function of the sea urchin major yolk protein toposome.

PubMed

Castellano, Immacolata; Migliaccio, Oriana; Ferraro, Giarita; Maffioli, Elisa; Marasco, Daniela; Merlino, Antonello; Zingone, Adriana; Tedeschi, Gabriella; Palumbo, Anna

2018-03-15

The major yolk protein toposome plays crucial roles during gametogenesis and development of sea urchins. We previously found that nitration of toposome increases in the gonads of a Paracentrotus lividus population living in a marine protected area affected by toxic blooms of Ostreospsis cf. ovata, compared to control populations. This modification is associated with ovatoxin accumulation, high levels of nitric oxide in the gonads, and a remarkable impairment of progeny development. However, nothing is known about the environmental-mediated-regulation of the structure and biological function of toposome. Here, we characterize through wide-ranging biochemical and structural analyses the nitrated toposome of sea urchins exposed to the bloom, and subsequently detoxified. The increased number of nitrated tyrosines in toposome of sea urchins collected during algal bloom induced structural changes and improvement of the Ca 2+ -binding affinity of the protein. After 3 months' detoxification, ovatoxin was undetectable, and the number of nitric oxide-modified tyrosines was reduced. However, the nitration of specific residues was irreversible and occurred also in embryos treated with metals, used as a proxy of environmental pollutants. The structural and functional changes of toposome caused by nitration under adverse environmental conditions may be related to the defective development of sea urchins' progeny.

A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development

PubMed Central

Covassin, L. D.; Siekmann, A. F.; Kacergis, M. C.; Laver, E.; Moore, J. C.; Villefranc, J. A.; Weinstein, B. M.; Lawson, N. D.

2009-01-01

In this work we describe a forward genetic approach to identify mutations that affect blood vessel development in the zebrafish. By applying a haploid screening strategy in a transgenic background that allows direct visualization of blood vessels, it was possible to identify several classes of mutant vascular phenotypes. Subsequent characterization of mutant lines revealed that defects in Vascular endothelial growth factor (Vegf) signaling specifically affected artery development. Comparison of phenotypes associated with different mutations within a functional zebrafish Vegf receptor-2 ortholog (referred to as kdr-like, kdrl) revealed surprisingly varied effects on vascular development. In parallel, we identified an allelic series of mutations in phospholipase c gamma 1 (plcg1). Together with in vivo structure-function analysis, our results suggest a requirement for Plcg1 catalytic activity downstream of receptor tyrosine kinases. We further find that embryos lacking both maternal and zygotic plcg1 display more severe defects in artery differentiation but are otherwise similar to zygotic mutants. Finally, we demonstrate through mosaic analysis that plcg1 functions autonomously in endothelial cells. Together our genetic analyses suggest that Vegf/Plcg1 signaling acts at multiple time points and in different signaling contexts to mediate distinct aspects of artery development. PMID:19269286

FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network

PubMed Central

Qin, Wei; Tian, Jie; Bai, Lijun; Pan, Xiaohong; Yang, Lin; Chen, Peng; Dai, Jianping; Ai, Lin; Zhao, Baixiao; Gong, Qiyong; Wang, Wei; von Deneen, Karen M; Liu, Yijun

2008-01-01

Background Recently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear. Results In the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network. Conclusion Our findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation. PMID:19014532

Earlier adolescent substance use onset predicts stronger connectivity between reward and cognitive control brain networks.

PubMed

Weissman, David G; Schriber, Roberta A; Fassbender, Catherine; Atherton, Olivia; Krafft, Cynthia; Robins, Richard W; Hastings, Paul D; Guyer, Amanda E

2015-12-01

Early adolescent onset of substance use is a robust predictor of future substance use disorders. We examined the relation between age of substance use initiation and resting state functional connectivity (RSFC) of the core reward processing (nucleus accumbens; NAcc) to cognitive control (prefrontal cortex; PFC) brain networks. Adolescents in a longitudinal study of Mexican-origin youth reported their substance use annually from ages 10 to 16 years. At age 16, 69 adolescents participated in a resting state functional magnetic resonance imaging scan. Seed-based correlational analyses were conducted using regions of interest in bilateral NAcc. The earlier that adolescents initiated substance use, the stronger the connectivity between bilateral NAcc and right dorsolateral PFC, right dorsomedial PFC, right pre-supplementary motor area, right inferior parietal lobule, and left medial temporal gyrus. The regions that demonstrated significant positive linear relationships between the number of adolescent years using substances and connectivity with NAcc are nodes in the right frontoparietal network, which is central to cognitive control. The coupling of reward and cognitive control networks may be a mechanism through which earlier onset of substance use is related to brain function over time, a trajectory that may be implicated in subsequent substance use disorders. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Large-scale DCMs for resting-state fMRI.

PubMed

Razi, Adeel; Seghier, Mohamed L; Zhou, Yuan; McColgan, Peter; Zeidman, Peter; Park, Hae-Jeong; Sporns, Olaf; Rees, Geraint; Friston, Karl J

2017-01-01

This paper considers the identification of large directed graphs for resting-state brain networks based on biophysical models of distributed neuronal activity, that is, effective connectivity . This identification can be contrasted with functional connectivity methods based on symmetric correlations that are ubiquitous in resting-state functional MRI (fMRI). We use spectral dynamic causal modeling (DCM) to invert large graphs comprising dozens of nodes or regions. The ensuing graphs are directed and weighted, hence providing a neurobiologically plausible characterization of connectivity in terms of excitatory and inhibitory coupling. Furthermore, we show that the use of to discover the most likely sparse graph (or model) from a parent (e.g., fully connected) graph eschews the arbitrary thresholding often applied to large symmetric (functional connectivity) graphs. Using empirical fMRI data, we show that spectral DCM furnishes connectivity estimates on large graphs that correlate strongly with the estimates provided by stochastic DCM. Furthermore, we increase the efficiency of model inversion using functional connectivity modes to place prior constraints on effective connectivity. In other words, we use a small number of modes to finesse the potentially redundant parameterization of large DCMs. We show that spectral DCM-with functional connectivity priors-is ideally suited for directed graph theoretic analyses of resting-state fMRI. We envision that directed graphs will prove useful in understanding the psychopathology and pathophysiology of neurodegenerative and neurodevelopmental disorders. We will demonstrate the utility of large directed graphs in clinical populations in subsequent reports, using the procedures described in this paper.

Eigenanalysis and Graph Theory Combined to Determine the Seasonal and Solar-Cycle Variations of Polar Magnetic Fields

NASA Astrophysics Data System (ADS)

Shore, R. M.; Freeman, M. P.; Gjerloev, J. W.

2017-12-01

We apply the meteorological analysis method of Empirical Orthogonal Functions (EOF) to ground magnetometer measurements, and subsequently use graph theory to classify the results. The EOF method is used to characterise and separate contributions to the variability of the Earth's external magnetic field (EMF) in the northern polar region. EOFs decompose the noisy EMF data into a small number of independent spatio-temporal basis functions, which collectively describe the majority of the magnetic field variance. We use these basis functions (computed monthly) to infill where data are missing, providing a self-consistent description of the EMF at 5-minute resolution spanning 1997-2009 (solar cycle 23). The EOF basis functions are calculated independently for each of the 144 months (i.e. 1997-2009) analysed. Since (by definition) the basis vectors are ranked by their contribution to the total variance, their rank will change from month to month. We use graph theory to find clusters of quantifiably-similar spatial basis functions, and thereby track similar patterns throughout the span of 144 months. We find that the discovered clusters can be associated with well-known individual Disturbance Polar (DP)-type equivalent current systems (e.g. DP2, DP1, DPY, NBZ), or with the motion of these systems. Via this method, we thus describe the varying behaviour of these current systems over solar cycle 23. We present their seasonal and solar cycle variations and examine the response of each current system to solar wind driving.

Does the presence of priming hinder subsequent recognition or recall performance?

PubMed

Stark, Shauna M; Gordon, Barry; Stark, Craig E L

2008-02-01

Declarative and non-declarative memories are thought be supported by two distinct memory systems that are often posited not to interact. However, Wagner, Maril, and Schacter (2000a) reported that at the time priming was assessed, greater behavioural and neural priming was associated with lower levels of subsequent recognition memory, demonstrating an interaction between declarative and non-declarative memory. We examined this finding using a similar paradigm, in which participants made the same or different semantic word judgements following a short or long lag and subsequent memory test. We found a similar overall pattern of results, with greater behavioural priming associated with a decrease in recognition and recall performance. However, neither various within-participant nor various between-participant analyses revealed significant correlations between priming and subsequent memory performance. These data suggest that both lag and task have effects on priming and declarative memory performance, but that they are largely independent and occur in parallel.

Comparative genomic analysis of retrogene repertoire in two green algae Volvox carteri and Chlamydomonas reinhardtii.

PubMed

Jąkalski, Marcin; Takeshita, Kazutaka; Deblieck, Mathieu; Koyanagi, Kanako O; Makałowska, Izabela; Watanabe, Hidemi; Makałowski, Wojciech

2016-08-04

Retroposition, one of the processes of copying the genetic material, is an important RNA-mediated mechanism leading to the emergence of new genes. Because the transcription controlling segments are usually not copied to the new location in this mechanism, the duplicated gene copies (retrocopies) become pseudogenized. However, few can still survive, e.g. by recruiting novel regulatory elements from the region of insertion. Subsequently, these duplicated genes can contribute to the formation of lineage-specific traits and phenotypic diversity. Despite the numerous studies of the functional retrocopies (retrogenes) in animals and plants, very little is known about their presence in green algae, including morphologically diverse species. The current availability of the genomes of both uni- and multicellular algae provides a good opportunity to conduct a genome-wide investigation in order to fill the knowledge gap in retroposition phenomenon in this lineage. Here we present a comparative genomic analysis of uni- and multicellular algae, Chlamydomonas reinhardtii and Volvox carteri, respectively, to explore their retrogene complements. By adopting a computational approach, we identified 141 retrogene candidates in total in both genomes, with their fraction being significantly higher in the multicellular Volvox. Majority of the retrogene candidates showed signatures of functional constraints, thus indicating their functionality. Detailed analyses of the identified retrogene candidates, their parental genes, and homologs of both, revealed that most of the retrogene candidates were derived from ancient retroposition events in the common ancestor of the two algae and that the parental genes were subsequently lost from the respective lineages, making many retrogenes 'orphan'. We revealed that the genomes of the green algae have maintained many possibly functional retrogenes in spite of experiencing various molecular evolutionary events during a long evolutionary time after the retroposition events. Our first report about the retrogene set in the green algae provides a good foundation for any future investigation of the repertoire of retrogenes and facilitates the assessment of the evolutionary impact of retroposition on diverse morphological traits in this lineage. This article was reviewed by William Martin and Piotr Zielenkiewicz.

The impact of ADHD symptoms and global impairment in childhood on working disability in mid-adulthood: a 28-year follow-up study using official disability pension records in a high-risk in-patient population

PubMed Central

2012-01-01

Background Individuals with ADHD have been associated with more employment difficulties in early adulthood than healthy community controls. To examine whether this association is attributable specifically to disturbance of activity and attention (ADHD) or to psychopathology in general, we wanted to extend existing research by comparing the rate of mid-adulthood working disabilities for individuals diagnosed with ADHD as children with the rate for clinical controls diagnosed with either conduct disorder, emotional disorder or mixed disorder of conduct and emotions. Methods Former Norwegian child-psychiatric in-patients (n = 257) were followed up 17–39 years after hospitalization by record linkage to the Norwegian national registry of disability pension (DP) awards. Based on the hospital records, the patients were re-diagnosed according to ICD-10. Associations between the diagnoses, other baseline factors and subsequent DP were investigated using Kaplan–Meier survival analyses and logrank testing. Results At follow-up, 19% of the participants had received a DP award. In the logrank testing, ADHD was the only disorder associated with a subsequent DP, with 30% being disabled at follow-up (p = 0.01). Low psychosocial functioning (assessed by the Children’s Global Assessment Scale) at admission uniquely predicted future DP (p = 0.04). Conclusions ADHD in childhood was highly associated with later receiving a DP. Our finding of worse prognosis in ADHD compared with other internalizing and externalizing disorders in mid-adulthood supports the assumption of ADHD being specifically linked to working disability. Assessment of psychosocial functioning in addition to diagnostic features could enhance prediction of children who are most at risk of future disability. PMID:23083209

Achieving simplified disease activity index remission in patients with active rheumatoid arthritis is associated with subsequent good functional and structural outcomes in a real-world clinical setting under a treat-to-target strategy.

PubMed

Hirano, Fumio; Yokoyama, Waka; Yamazaki, Hayato; Amano, Koichi; Kawakami, Atsushi; Hayashi, Taichi; Tamura, Naoto; Yasuda, Shinsuke; Dobashi, Hiroaki; Fujii, Takao; Ito, Satoshi; Kaneko, Yuko; Matsui, Toshihiro; Okuda, Yasuaki; Saito, Kazuyoshi; Suzuki, Fumihito; Yoshimi, Ryusuke; Sakai, Ryoko; Koike, Ryuji; Kohsaka, Hitoshi; Miyasaka, Nobuyuki; Harigai, Masayoshi

2017-09-01

To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T). In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS) 

Analysis of Glycoproteins in Human Serum by Means of Glycospecific Magnetic Bead Separation and LC-MALDI-TOF/TOF Analysis with Automated Glycopeptide Detection

PubMed Central

Sparbier, Katrin; Asperger, Arndt; Resemann, Anja; Kessler, Irina; Koch, Sonja; Wenzel, Thomas; Stein, Günter; Vorwerg, Lars; Suckau, Detlev; Kostrzewa, Markus

2007-01-01

Comprehensive proteomic analyses require efficient and selective pre-fractionation to facilitate analysis of post-translationally modified peptides and proteins, and automated analysis workflows enabling the detection, identification, and structural characterization of the corresponding peptide modifications. Human serum contains a high number of glycoproteins, comprising several orders of magnitude in concentration. Thereby, isolation and subsequent identification of low-abundant glycoproteins from serum is a challenging task. selective capturing of glycopeptides and -proteins was attained by means of magnetic particles specifically functionalized with lectins or boronic acids that bind to various structural motifs. Human serum was incubated with differentially functionalized magnetic micro-particles (lectins or boronic acids), and isolated proteins were digested with trypsin. Subsequently, the resulting complex mixture of peptides and glycopeptides was subjected to LC-MALDI analysis and database searching. In parallel, a second magnetic bead capturing was performed on the peptide level to separate and analyze by LC-MALDI intact glycopeptides, both peptide sequence and glycan structure. Detection of glycopeptides was achieved by means of a software algorithm that allows extraction and characterization of potential glycopeptide candidates from large LC-MALDI-MS/MS data sets, based on N-glycopeptide-specific fragmentation patterns and characteristic fragment mass peaks, respectively. By means of fast and simple glycospecific capturing applied in conjunction with extensive LC-MALDI-MS/MS analysis and novel data analysis tools, a high number of low-abundant proteins were identified, comprising known or predicted glycosylation sites. According to the specific binding preferences of the different types of beads, complementary results were obtained from the experiments using either magnetic ConA-, LCA-, WGA-, and boronic acid beads, respectively. PMID:17916798

Predicting Treatment Response in Social Anxiety Disorder From Functional Magnetic Resonance Imaging

PubMed Central

Doehrmann, Oliver; Ghosh, Satrajit S.; Polli, Frida E.; Reynolds, Gretchen O.; Horn, Franziska; Keshavan, Anisha; Triantafyllou, Christina; Saygin, Zeynep M.; Whitfield-Gabrieli, Susan; Hofmann, Stefan G.; Pollack, Mark; Gabrieli, John D.

2013-01-01

Context Current behavioral measures poorly predict treatment outcome in social anxiety disorder (SAD). To our knowledge, this is the first study to examine neuroimaging-based treatment prediction in SAD. Objective To measure brain activation in patients with SAD as a biomarker to predict subsequent response to cognitive behavioral therapy (CBT). Design Functional magnetic resonance imaging (fMRI) data were collected prior to CBT intervention. Changes in clinical status were regressed on brain responses and tested for selectivity for social stimuli. Setting Patients were treated with protocol-based CBT at anxiety disorder programs at Boston University or Massachusetts General Hospital and underwent neuroimaging data collection at Massachusetts Institute of Technology. Patients Thirty-nine medication-free patients meeting DSM-IV criteria for the generalized subtype of SAD. Interventions Brain responses to angry vs neutral faces or emotional vs neutral scenes were examined with fMRI prior to initiation of CBT. Main Outcome Measures Whole-brain regression analyses with differential fMRI responses for angry vs neutral faces and changes in Liebowitz Social Anxiety Scale score as the treatment outcome measure. Results Pretreatment responses significantly predicted subsequent treatment outcome of patients selectively for social stimuli and particularly in regions of higher-order visual cortex. Combining the brain measures with information on clinical severity accounted for more than 40% of the variance in treatment response and substantially exceeded predictions based on clinical measures at baseline. Prediction success was unaffected by testing for potential confounding factors such as depression severity at baseline. Conclusions The results suggest that brain imaging can provide biomarkers that substantially improve predictions for the success of cognitive behavioral interventions and more generally suggest that such biomarkers may offer evidence-based, personalized medicine approaches for optimally selecting among treatment options for a patient. PMID:22945462

The impact of ADHD symptoms and global impairment in childhood on working disability in mid-adulthood: a 28-year follow-up study using official disability pension records in a high-risk in-patient population.

PubMed

Mordre, Marianne; Groholt, Berit; Sandstad, Berit; Myhre, Anne Margrethe

2012-10-19

Individuals with ADHD have been associated with more employment difficulties in early adulthood than healthy community controls. To examine whether this association is attributable specifically to disturbance of activity and attention (ADHD) or to psychopathology in general, we wanted to extend existing research by comparing the rate of mid-adulthood working disabilities for individuals diagnosed with ADHD as children with the rate for clinical controls diagnosed with either conduct disorder, emotional disorder or mixed disorder of conduct and emotions. Former Norwegian child-psychiatric in-patients (n = 257) were followed up 17-39 years after hospitalization by record linkage to the Norwegian national registry of disability pension (DP) awards. Based on the hospital records, the patients were re-diagnosed according to ICD-10. Associations between the diagnoses, other baseline factors and subsequent DP were investigated using Kaplan-Meier survival analyses and logrank testing. At follow-up, 19% of the participants had received a DP award. In the logrank testing, ADHD was the only disorder associated with a subsequent DP, with 30% being disabled at follow-up (p = 0.01). Low psychosocial functioning (assessed by the Children's Global Assessment Scale) at admission uniquely predicted future DP (p = 0.04). ADHD in childhood was highly associated with later receiving a DP. Our finding of worse prognosis in ADHD compared with other internalizing and externalizing disorders in mid-adulthood supports the assumption of ADHD being specifically linked to working disability. Assessment of psychosocial functioning in addition to diagnostic features could enhance prediction of children who are most at risk of future disability.

Remembering beauty: roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces.

PubMed

Tsukiura, Takashi; Cabeza, Roberto

2011-01-01

Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent misses

Remembering beauty: Roles of orbitofrontal and hippocampal regions in successful memory encoding of attractive faces

PubMed Central

Tsukiura, Takashi; Cabeza, Roberto

2010-01-01

Behavioral data have shown that attractive faces are better remembered but the neural mechanisms of this effect are largely unknown. To investigate this issue, female participants were scanned with event-related functional MRI (fMRI) while rating the attractiveness of male faces. Memory for the faces was tested after fMRI scanning and was used to identify successful encoding activity (subsequent memory paradigm). As expected, attractive faces were remembered better than other faces. The study yielded three main fMRI findings. First, activity in the right orbitofrontal cortex increased linearly as a function of attractiveness ratings. Second, activity in the left hippocampus increased as a function of subsequent memory (subsequent misses

5-a-day fruit and vegetable food product labels: reduced fruit and vegetable consumption following an exaggerated compared to a modest label.

PubMed

Appleton, K M; Pidgeon, H J

2018-05-15

Food product labels based on the WHO 5-a-day fruit and vegetable (FV) message are becoming increasingly common, but these labels may impact negatively on complementary or subsequent FV consumption. This study aimed to investigate the impact of a '3 of your 5-a-day' versus a '1 of your 5-a-day' smoothie product label on subsequent FV consumption. Using an acute experimental design, 194 participants (90 males, 104 females) were randomised to consume a smoothie labelled as either '3 of your 5-a-day' (N = 97) or '1 of your 5-a-day' (N = 97) in full, following a usual breakfast. Subsequent FV consumption was measured for the rest of the day using 24-h recall. Usual FV consumption was also assessed via 24-h recall for the day before the study. Regression analyses revealed a significantly lower subsequent FV consumption following smoothies displaying the '3 of your 5-a-day' label compared to the '1 of your 5-a-day' label (Beta = - 0.15, p = 0.04). Secondary analyses revealed these effects to be driven mainly by changes to consumption in usual high FV consumers, in females and in vegetable as opposed to fruit consumption. These findings demonstrate a role for label information in food intake, and the potential negative impacts of an exaggerated food product label on healthy food consumption and healthy dietary profiles.

Core/shell CuO/Al Nanorods Thermite Film Based on Electrochemical Anodization.

PubMed

Yu, Chunpei; Zhang, Wenchao; Hu, Bin; Ni, Debin; Zheng, Zilong; Liu, Jingping; Ma, Kefeng; Ren, Wei

2018-06-13

In this study, a new method was reported for the fabrication of the nanostructured CuO/Al thermite film on the Cu substrate. The CuO nanorods (NRs) arrays vertically grew from the Cu surfaces by electrochemical anodization processes, followed by the deposition of an Al layer on the CuO NRs via magnetron sputtering to form a core/shell CuO/Al nanothermite film, whose component, structure and morphology were subsequently characterized. In addition, the energy-release characteristics of the obtained nanothermite film was investigated using thermal analyses and laser ignition tests. All evidences demonstrate that the obtained CuO/Al is of a uniform structure and superb energy performance. Impressively, this resulted material is potentially useful in the applications of functional energetic chips due to its easy integration with microelectromechanical systems (MEMS) technologies. © 2018 IOP Publishing Ltd.

Reliability of the individual components of the Canadian Armed Forces Physical Employment Standard.

PubMed

Stockbrugger, Barry G; Reilly, Tara J; Blacklock, Rachel E; Gagnon, Patrick J

2018-01-29

This investigation recruited 24 participants from both the Canadian Armed Forces (CAF) and civilian populations to complete 4 separate trials at "best effort" of each of the 4 components in the CAF Physical Employment Standard named the FORCE Evaluation: Fitness for Operational Requirements of CAF Employment. Analyses were performed to examine the level of variability and reliability within each component. The results demonstrate that candidates should be provided with at least 1 retest if they have recently completed at least 2 previous best effort attempts as per the protocol. In addition, the minimal detectable difference is given for each of the 4 components in seconds which identifies the threshold for subsequent action, either retest or remedial training, for those unable to meet the minimum standard. These results will educate the delivery of this employment standard, function as a method of accommodation, in addition to providing direction for physical training programs.

Early adolescents show sustained susceptibility to cognitive interference by emotional distractors.

PubMed

Heim, Sabine; Ihssen, Niklas; Hasselhorn, Marcus; Keil, Andreas

2013-01-01

A child's ability to continuously pay attention to a cognitive task is often challenged by distracting events. Distraction is especially detrimental in a learning or classroom environment in which attended information is typically associated with establishing skills and knowledge. Here we report a study examining the effect of emotional distractors on performance in a subsequent visual lexical decision task in 11- to 13-year-old students (n=30). Lexical decisions about neutral verbs and verb-like pseudowords (i.e., targets) were analysed as a function of the preceding distractor type (pleasant, neutral, or unpleasant photos) and the picture-target stimulus-onset asynchrony (SOA; 200 or 600 ms). Across distractor categories, emotionally arousing pictures prolonged decisions about word targets when compared to neutral pictures, irrespective of the SOA. The present results demonstrate that similar to adults, early adolescent students exhibit sustained susceptibility to cognitive interference by irrelevant emotional events.

Isolation of plasmodesmata from Arabidopsis suspension culture cells.

PubMed

Grison, Magali S; Fernandez-Calvino, Lourdes; Mongrand, Sébastien; Bayer, Emmanuelle M F

2015-01-01

Due to their position firmly anchored within the plant cell wall, plasmodesmata (PD) are notoriously difficult to isolate from plant tissue. Yet, getting access to isolated PD represents the most straightforward strategy for the identification of their molecular components. Proteomic and lipidomic analyses of such PD fractions have provided and will continue to provide critical information on the functional and structural elements that define these membranous nano-pores. Here, we describe a two-step simple purification procedure that allows isolation of pure PD-derived membranes from Arabidopsis suspension cells. The first step of this procedure consists in isolating cell wall fragments containing intact PD while free of contamination from other cellular compartments. The second step relies on an enzymatic degradation of the wall matrix and the subsequent release of "free" PD. Isolated PD membranes provide a suitable starting material for the analysis of PD-associated proteins and lipids.

The Influence of Statistical versus Exemplar Appeals on Indian Adults' Health Intentions: An Investigation of Direct Effects and Intervening Persuasion Processes.

PubMed

McKinley, Christopher J; Limbu, Yam; Jayachandran, C N

2017-04-01

In two separate investigations, we examined the persuasive effectiveness of statistical versus exemplar appeals on Indian adults' smoking cessation and mammography screening intentions. To more comprehensively address persuasion processes, we explored whether message response and perceived message effectiveness functioned as antecedents to persuasive effects. Results showed that statistical appeals led to higher levels of health intentions than exemplar appeals. In addition, findings from both studies indicated that statistical appeals stimulated more attention and were perceived as more effective than anecdotal accounts. Among male smokers, statistical appeals also generated greater cognitive processing than exemplar appeals. Subsequent mediation analyses revealed that message response and perceived message effectiveness fully carried the influence of appeal format on health intentions. Given these findings, future public health initiatives conducted among similar populations should design messages that include substantive factual information while ensuring that this content is perceived as credible and valuable.

Microscopic stress characterisation of functional iron-based alloys by white X-ray microbeam diffraction

NASA Astrophysics Data System (ADS)

Kwon, E. P.; Sato, S.; Fujieda, S.; Shinoda, K.; Kajiwara, K.; Sato, M.; Suzuki, S.

2018-01-01

Microscopic residual stress evolution in an austenite (γ) grain during a shape-memory process in an Fe-Mn-Si-Cr alloy was investigated using the white X-ray microbeam diffraction technique. The stresses were measured on a coarse grain, which had an orientation near <144>, parallel to the tensile loading direction with a high Schmid factor for a martensitic transformation. The magnitude of the residual stresses in a grain of the sample, which was subjected to a 23 % tensile strain and subsequent shape-recovery heating, was found to be very small and comparable to that prior to tensile deformation. Measurements of the recovery strain and microstructural analyses using electron backscatter diffraction suggested that the low residual stresses could be attributed to the significant shape recovery caused by a highly reversible martensitic transformation in the grain with a particular orientation.

Sonochemically Fabricated Microelectrode Arrays for Use as Sensing Platforms

PubMed Central

Collyer, Stuart D.; Davis, Frank; Higson, Séamus P.J.

2010-01-01

The development, manufacture, modification and subsequent utilisation of sonochemically-formed microelectrode arrays is described for a range of applications. Initial fabrication of the sensing platform utilises ultrasonic ablation of electrochemically insulating polymers deposited upon conductive carbon substrates, forming an array of up to 70,000 microelectrode pores cm−2. Electrochemical and optical analyses using these arrays, their enhanced signal response and stir-independence area are all discussed. The growth of conducting polymeric “mushroom” protrusion arrays with entrapped biological entities, thereby forming biosensors is detailed. The simplicity and inexpensiveness of this approach, lending itself ideally to mass fabrication coupled with unrivalled sensitivity and stir independence makes commercial viability of this process a reality. Application of microelectrode arrays as functional components within sensors include devices for detection of chlorine, glucose, ethanol and pesticides. Immunosensors based on microelectrode arrays are described within this monograph for antigens associated with prostate cancer and transient ischemic attacks (strokes). PMID:22399926

STR-validator: an open source platform for validation and process control.

PubMed

Hansson, Oskar; Gill, Peter; Egeland, Thore

2014-11-01

This paper addresses two problems faced when short tandem repeat (STR) systems are validated for forensic purposes: (1) validation is extremely time consuming and expensive, and (2) there is strong consensus about what to validate but not how. The first problem is solved by powerful data processing functions to automate calculations. Utilising an easy-to-use graphical user interface, strvalidator (hereafter referred to as STR-validator) can greatly increase the speed of validation. The second problem is exemplified by a series of analyses, and subsequent comparison with published material, highlighting the need for a common validation platform. If adopted by the forensic community STR-validator has the potential to standardise the analysis of validation data. This would not only facilitate information exchange but also increase the pace at which laboratories are able to switch to new technology. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Brain structural connectivity increases concurrent with functional improvement: evidence from diffusion tensor MRI in children with cerebral palsy during therapy.

PubMed

Englander, Zoë A; Sun, Jessica; Laura Case; Mikati, Mohamad A; Kurtzberg, Joanne; Song, Allen W

2015-01-01

Cerebral Palsy (CP) refers to a heterogeneous group of permanent but non-progressive movement disorders caused by injury to the developing fetal or infant brain (Bax et al., 2005). Because of its serious long-term consequences, effective interventions that can help improve motor function, independence, and quality of life are critically needed. Our ongoing longitudinal clinical trial to treat children with CP is specifically designed to meet this challenge. To maximize the potential for functional improvement, all children in this trial received autologous cord blood transfusions (with order randomized with a placebo administration over 2 years) in conjunction with more standard physical and occupational therapies. As a part of this trial, magnetic resonance imaging (MRI) is used to improve our understanding of how these interventions affect brain development, and to develop biomarkers of treatment efficacy. In this report, diffusion tensor imaging (DTI) and subsequent brain connectome analyses were performed in a subset of children enrolled in the clinical trial (n = 17), who all exhibited positive but varying degrees of functional improvement over the first 2-year period of the study. Strong correlations between increases in white matter (WM) connectivity and functional improvement were demonstrated; however no significant relationships between either of these factors with the age of the child at time of enrollment were identified. Thus, our data indicate that increases in brain connectivity reflect improved functional abilities in children with CP. In future work, this potential biomarker can be used to help differentiate the underlying mechanisms of functional improvement, as well as to identify treatments that can best facilitate functional improvement upon un-blinding of the timing of autologous cord blood transfusions at the completion of this study.

General anaesthesia-induced anaphylaxis: impact of allergy testing on subsequent anaesthesia.

PubMed

Trautmann, A; Seidl, C; Stoevesandt, J; Seitz, C S

2016-01-01

Immunoglobulin E-mediated allergy to drugs and substances used during general anaesthesia as well as non-allergic drug hypersensitivity reactions may account for anaesthesia-induced anaphylaxis. As IgE-mediated anaphylaxis is a potentially life-threatening reaction, identification of the culprit allergen is essential to avoid anaphylaxis recurrence during subsequent general anaesthesia. To study whether preventive recommendations derived from allergy testing after intraoperative anaphylaxis were followed in subsequent general anaesthesia. Results of standardized allergy testing after anaesthesia-induced anaphylaxis and outcome of subsequent general anaesthesia were analysed retrospectively. Fifty-three of 107 patients were diagnosed with IgE-mediated allergy to a drug or substance used during general anaesthesia, and 54 patients were test negative. Twenty-eight of 29 allergy patients tolerated subsequent general anaesthesia uneventfully. One patient with cefazolin allergy suffered from anaphylaxis recurrence due to accidental reapplication of cefazolin. Twenty-two of 24 test-negative patients tolerated subsequent general anaesthesia, whereas two patients again developed anaphylaxis despite pre-medication regimens. Our results confirm the practical impact of allergy testing in general anaesthesia-induced anaphylaxis. By identification of the allergen, it is possible to avoid allergic anaphylaxis during subsequent anaesthesia. In most cases, recommended pre-medication seems to prevent the recurrence of non-allergic drug hypersensitivity reactions. © 2015 John Wiley & Sons Ltd.

Intraoperative Transesophageal Echocardiography and Right Ventricular Failure After Left Ventricular Assist Device Implantation.

PubMed

Silverton, Natalie A; Patel, Ravi; Zimmerman, Josh; Ma, Jianing; Stoddard, Greg; Selzman, Craig; Morrissey, Candice K

2018-02-15

To determine whether intraoperative measures of right ventricular (RV) function using transesophageal echocardiography are associated with subsequent RV failure after left ventricular assist device (LVAD) implantation. Retrospective, nonrandomized, observational study. Single tertiary-level, university-affiliated hospital. The study comprised 100 patients with systolic heart failure undergoing elective LVAD implantation. Transesophageal echocardiographic images before and after cardiopulmonary bypass were analyzed to quantify RV function using tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S'), fractional area change (FAC), RV global longitudinal strain, and RV free wall strain. A chart review was performed to determine which patients subsequently developed RV failure (right ventricular assist device placement or prolonged inotrope requirement ≥14 days). Nineteen patients (19%) subsequently developed RV failure. Postbypass FAC was the only measure of RV function that distinguished between the RV failure and non-RV failure groups (21.2% v 26.5%; p = 0.04). The sensitivity, specificity, and area under the curve of an abnormal RV FAC (<35%) for RV failure after LVAD implantation were 84%, 20%, and 0.52, respectively. No other intraoperative measure of RV function was associated with subsequent RV failure. RV failure increased ventilator time, intensive care unit and hospital length of stay, and mortality. Intraoperative measures of RV function such as tricuspid annular plane systolic excursion, tricuspid annular systolic velocity, and RV strain were not associated with RV failure after LVAD implantation. Decreased postbypass FAC was significantly associated with RV failure but showed poor discrimination. Copyright © 2018 Elsevier Inc. All rights reserved.

Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

PubMed

Guo, Yong; Qiu, Li-Juan

2013-01-01

The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max). In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs) were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

Semen molecular and cellular features: these parameters can reliably predict subsequent ART outcome in a goat model

PubMed Central

Berlinguer, Fiammetta; Madeddu, Manuela; Pasciu, Valeria; Succu, Sara; Spezzigu, Antonio; Satta, Valentina; Mereu, Paolo; Leoni, Giovanni G; Naitana, Salvatore

2009-01-01

Currently, the assessment of sperm function in a raw or processed semen sample is not able to reliably predict sperm ability to withstand freezing and thawing procedures and in vivo fertility and/or assisted reproductive biotechnologies (ART) outcome. The aim of the present study was to investigate which parameters among a battery of analyses could predict subsequent spermatozoa in vitro fertilization ability and hence blastocyst output in a goat model. Ejaculates were obtained by artificial vagina from 3 adult goats (Capra hircus) aged 2 years (A, B and C). In order to assess the predictive value of viability, computer assisted sperm analyzer (CASA) motility parameters and ATP intracellular concentration before and after thawing and of DNA integrity after thawing on subsequent embryo output after an in vitro fertility test, a logistic regression analysis was used. Individual differences in semen parameters were evident for semen viability after thawing and DNA integrity. Results of IVF test showed that spermatozoa collected from A and B lead to higher cleavage rates (0 < 0.01) and blastocysts output (p < 0.05) compared with C. Logistic regression analysis model explained a deviance of 72% (p < 0.0001), directly related with the mean percentage of rapid spermatozoa in fresh semen (p < 0.01), semen viability after thawing (p < 0.01), and with two of the three comet parameters considered, i.e tail DNA percentage and comet length (p < 0.0001). DNA integrity alone had a high predictive value on IVF outcome with frozen/thawed semen (deviance explained: 57%). The model proposed here represents one of the many possible ways to explain differences found in embryo output following IVF with different semen donors and may represent a useful tool to select the most suitable donors for semen cryopreservation. PMID:19900288

An analytical biomarker for treatment of patients with recurrent B-ALL after remission induced by infusion of anti-CD19 chimeric antigen receptor T (CAR-T) cells.

PubMed

Zhang, Yajing; Zhang, Wenying; Dai, Hanren; Wang, Yao; Shi, Fengxia; Wang, Chunmeng; Guo, Yelei; Liu, Yang; Chen, Meixia; Feng, Kaichao; Zhang, Yan; Liu, Chuanjie; Yang, Qingming; Li, Suxia; Han, Weidong

2016-04-01

Anti-CD19 chimeric antigen receptor-modified T (CAR-T-19) cells have emerged as a powerful targeted immunotherapy for B-cell lineage acute lymphoblastic leukemia with a remarkable clinical response in recent trials. Nonetheless, few data are available on the subsequent clinical monitoring and treatment of the patients, especially those with disease recurrence after CAR-T-19 cell infusion. Here, we analyzed three patients who survived after our phase I clinical trial and who were studied by means of biomarkers reflecting persistence of CAR-T-19 cells in vivo and predictive factors directing further treatment. One patient achieved 9-week sustained complete remission and subsequently received an allogeneic hematopoietic stem cell transplant. Another patient who showed relapse after 20 weeks without detectable leukemia in the cerebrospinal fluid after CAR-T-19 cell treatment was able to achieve a morphological remission under the influence of stand-alone low-dose chemotherapeutic agents. The third patient gradually developed extensive extramedullary involvement in tissues with scarce immune- cell infiltration during a long period of hematopoietic remission after CAR-T-19 cell therapy. Long-term and discontinuous increases in serum cytokines (mainly interleukin 6 and C-reactive protein) were identified in two patients (Nos. 1 and 6) even though only a low copy number of CAR molecules could be detected in their peripheral blood. This finding was suggestive of persistent functional activity of CAR-T-19 cells. Combined analyses of laboratory biomarkers with their clinical manifestations before and after salvage treatment showed that the persistent immunosurveillance mediated by CAR-T-19 cells would inevitably potentiate the leukemia-killing effectiveness of subsequent chemotherapy in patients who showed relapse after CAR-T-19-induced remission.

Spatiotemporal sensitivity analysis of vertical transport of pesticides in soil

EPA Science Inventory

Environmental fate and transport processes are influenced by many factors. Simulation models that mimic these processes often have complex implementations, which can lead to over-parameterization. Sensitivity analyses are subsequently used to identify critical parameters whose un...

Analyses of a whole-genome inter-clade recombination map of hepatitis delta virus suggest a host polymerase-driven and viral RNA structure-promoted template-switching mechanism for viral RNA recombination

PubMed Central

Chao, Mei; Wang, Tzu-Chi; Lin, Chia-Chi; Yung-Liang Wang, Robert; Lin, Wen-Bin; Lee, Shang-En; Cheng, Ying-Yu; Yeh, Chau-Ting; Iang, Shan-Bei

2017-01-01

The genome of hepatitis delta virus (HDV) is a 1.7-kb single-stranded circular RNA that folds into an unbranched rod-like structure and has ribozyme activity. HDV redirects host RNA polymerase(s) (RNAP) to perform viral RNA-directed RNA transcription. RNA recombination is known to contribute to the genetic heterogeneity of HDV, but its molecular mechanism is poorly understood. Here, we established a whole-genome HDV-1/HDV-4 recombination map using two cloned sequences coexisting in cultured cells. Our functional analyses of the resulting chimeric delta antigens (the only viral-encoded protein) and recombinant genomes provide insights into how recombination promotes the genotypic and phenotypic diversity of HDV. Our examination of crossover distribution and subsequent mutagenesis analyses demonstrated that ribozyme activity on HDV genome, which is required for viral replication, also contributes to the generation of an inter-clade junction. These data provide circumstantial evidence supporting our contention that HDV RNA recombination occurs via a replication-dependent mechanism. Furthermore, we identify an intrinsic asymmetric bulge on the HDV genome, which appears to promote recombination events in the vicinity. We therefore propose a mammalian RNAP-driven and viral-RNA-structure-promoted template-switching mechanism for HDV genetic recombination. The present findings improve our understanding of the capacities of the host RNAP beyond typical DNA-directed transcription. PMID:28977829

Integrated Vehicle Ground Vibration Testing in Support of Launch Vehicle Loads and Controls Analysis

NASA Technical Reports Server (NTRS)

Askins, Bruce R.; Davis, Susan R.; Salyer, Blaine H.; Tuma, Margaret L.

2008-01-01

All structural systems possess a basic set of physical characteristics unique to that system. These unique physical characteristics include items such as mass distribution and damping. When specified, they allow engineers to understand and predict how a structural system behaves under given loading conditions and different methods of control. These physical properties of launch vehicles may be predicted by analysis or measured by certain types of tests. Generally, these properties are predicted by analysis during the design phase of a launch vehicle and then verified by testing before the vehicle becomes operational. A ground vibration test (GVT) is intended to measure by test the fundamental dynamic characteristics of launch vehicles during various phases of flight. During the series of tests, properties such as natural frequencies, mode shapes, and transfer functions are measured directly. These data will then be used to calibrate loads and control systems analysis models for verifying analyses of the launch vehicle. NASA manned launch vehicles have undergone ground vibration testing leading to the development of successful launch vehicles. A GVT was not performed on the inaugural launch of the unmanned Delta III which was lost during launch. Subsequent analyses indicated had a GVT been performed, it would have identified instability issues avoiding loss of the vehicle. This discussion will address GVT planning, set-up, execution and analyses, for the Saturn and Shuttle programs, and will also focus on the current and on-going planning for the Ares I and V Integrated Vehicle Ground Vibration Test (IVGVT).

Analysis of a G protein-coupled receptor for neurotensin by liquid chromatography-electrospray ionization-mass spectrometry.

PubMed

Ho, Jenny T C; White, Jim F; Grisshammer, Reinhard; Hess, Sonja

2008-05-01

The type 1 neurotensin receptor (NTS1) belongs to the G protein-coupled receptor (GPCR) family. GPCRs are involved in important physiological processes, but for many GPCRs ligand binding sites and other structural features have yet to be elucidated. Comprehensive analyses by mass spectrometry (MS) could address such issues, but they are complicated by the hydrophobic nature of the receptors. Recombinant NTS1 must be purified in the presence of detergents to maintain solubility and functionality of the receptor, to allow testing of ligand, or to allow G protein interaction. However, detergents are detrimental to MS analyses. Hence, steps need to be taken to substitute the detergents with MS-compatible polar/organic solvents. Here we report the characterization of NTS1 by electrospray ionization (ESI)-MS with emphasis on methods to transfer intact NTS1 or its proteolytic peptides into compatible solvents by protein precipitation and liquid chromatography (LC) prior to ESI-MS analyses. Molecular mass measurement of intact recombinant NTS1 was performed using a mixture of chloroform/methanol/aqueous trifluoroacetic acid as the mobile phase for size exclusion chromatography-ESI-MS analysis. In a separate experiment, NTS1 was digested with a combination of cyanogen bromide and trypsin and/or chymotrypsin. Subsequent reversed phase LC-ESI-tandem MS analysis resulted in greater than 80% sequence coverage of the NTS1 protein, including all seven transmembrane domains. This work represents the first comprehensive analysis of recombinant NTS1 using MS.

Mediator-dependent Nuclear Receptor Functions

PubMed Central

Chen, Wei; Roeder, Robert

2011-01-01

As gene-specific transcription factors, nuclear hormone receptors are broadly involved in many important biological processes. Their function on target genes requires the stepwise assembly of different coactivator complexes that facilitate chromatin remodeling and subsequent preinitiation complex (PIC) formation and function. Mediator has proved to be a crucial, and general, nuclear receptor-interacting coactivator, with demonstrated functions in transcription steps ranging from chromatin remodeling to subsequent PIC formation and function. Here we discuss (i) our current understanding of pathways that nuclear receptors and other interacting cofactors employ to recruit Mediator to target gene enhancers and promoters, including conditional requirements for the strong NR-Mediator interactions mediated by the NR AF2 domain and the MED1 LXXLLL motifs and (ii) mechanisms by which Mediator acts to transmit signals from enhancer-bound nuclear receptors to the general transcription machinery at core promoters to effect PIC formation and function. PMID:21854863

Organosilane functionalization of halloysite nanotubes for enhanced loading and controlled release.

PubMed

Yuan, Peng; Southon, Peter D; Liu, Zongwen; Kepert, Cameron J

2012-09-21

The surfaces of naturally occurring halloysite nanotubes were functionalized with γ-aminopropyltriethoxysilane (APTES), which was found to have a substantial effect on the loading and subsequent release of a model dye molecule. APTES was mostly anchored at the internal lumen surface of halloysite through covalent grafting, forming a functionalized surface covered by aminopropyl groups. The dye loading of the functionalized halloysite was 32% greater than that of the unmodified sample, and the release from the functionalized halloysite was dramatically prolonged as compared to that from the unmodified one. Dye release was prolonged at low pH and the release at pH 3.5 was approximately three times slower than that at pH 10.0. These results demonstrate that organosilane functionalization makes pH an external trigger for controlling the loading of guest on halloysite and the subsequent controlled release.

Mapping the pericentric heterochromatin by comparative genomic hybridization analysis and chromosome deletions in Drosophila melanogaster

PubMed Central

He, Bing; Caudy, Amy; Parsons, Lance; Rosebrock, Adam; Pane, Attilio; Raj, Sandeep; Wieschaus, Eric

2012-01-01

Heterochromatin represents a significant portion of eukaryotic genomes and has essential structural and regulatory functions. Its molecular organization is largely unknown due to difficulties in sequencing through and assembling repetitive sequences enriched in the heterochromatin. Here we developed a novel strategy using chromosomal rearrangements and embryonic phenotypes to position unmapped Drosophila melanogaster heterochromatic sequence to specific chromosomal regions. By excluding sequences that can be mapped to the assembled euchromatic arms, we identified sequences that are specific to heterochromatin and used them to design heterochromatin specific probes (“H-probes”) for microarray. By comparative genomic hybridization (CGH) analyses of embryos deficient for each chromosome or chromosome arm, we were able to map most of our H-probes to specific chromosome arms. We also positioned sequences mapped to the second and X chromosomes to finer intervals by analyzing smaller deletions with breakpoints in heterochromatin. Using this approach, we were able to map >40% (13.9 Mb) of the previously unmapped heterochromatin sequences assembled by the whole-genome sequencing effort on arm U and arm Uextra to specific locations. We also identified and mapped 110 kb of novel heterochromatic sequences. Subsequent analyses revealed that sequences located within different heterochromatic regions have distinct properties, such as sequence composition, degree of repetitiveness, and level of underreplication in polytenized tissues. Surprisingly, although heterochromatin is generally considered to be transcriptionally silent, we detected region-specific temporal patterns of transcription in heterochromatin during oogenesis and early embryonic development. Our study provides a useful approach to elucidate the molecular organization and function of heterochromatin and reveals region-specific variation of heterochromatin. PMID:22745230

Cumulative Trauma and Adjustment in Women Exposed to a Campus Shooting: Examining the Role of Appraisals and Social Support.

PubMed

Boykin, Derrecka M; Dunn, Qweandria T; Orcutt, Holly K

2017-05-01

Experiencing repeated trauma can have increasingly detrimental effects on psychosocial functioning after subsequent stressors. These effects may be intensified for victims of interpersonal traumas given that these events are often associated with heightened risk for adverse outcomes. To better understand this relationship, the present study prospectively examined the effect of pre-shooting trauma exposure (i.e., interpersonal vs. non-interpersonal trauma) on psychological functioning (i.e., posttraumatic stress symptoms, depression) following a mass campus shooting. Based on previous research, it was expected that negative appraisals and social support would mediate this relationship. A sample of 515 college women reporting prior trauma exposure was assessed at four time points following the shooting (i.e., pre-shooting, 1-month, 6-months, and 12-months post-shooting). Bootstrap analyses with bias-corrected confidence intervals were conducted. Contrary to expectation, pre-shooting trauma exposure was unrelated to 12-month post-shooting outcomes and neither negative appraisals nor social support at 6-months post-shooting emerged as mediators. Interestingly, a history of non-interpersonal trauma was associated with greater post-shooting family and friend support than a history of interpersonal trauma. Ad hoc analyses showed that pre-shooting symptom severity and level of exposure to the shooting had indirect effects on post-shooting outcomes via post-shooting negative appraisals. These findings support that cumulative trauma, regardless of type, may not have an additive effect unless individuals develop clinically significant symptoms following previous trauma. Trauma severity also appears to play a meaningful role.

Calciphylaxis: Beyond CKD-MBD.

PubMed

Fernández, María; Morales, Enrique; Gutierrez, Eduardo; Polanco, Natalia; Hernández, Eduardo; Mérida, Eva; Praga, Manuel

Calcific uraemic arteriolopathy (CUA), also called calciphylaxis, is a rare but potentially fatal vascular disorder that almost exclusively affects patients with chronic renal failure. The objective of this study was to analyse various risk factors for developing CUA and its subsequent clinical course according to the treatment received. A retrospective study that included patients diagnosed with CUA from December 1999 to December 2015. Various risk factors, clinical course and treatment options were analysed. A total of 28 patients (53.6% females) with a mean age of 67.2±11.8 (38-88) years were included. At the time of diagnosis, 53.6% were on haemodialysis, 25% were kidney transplant patients and 21.4% had normal renal function. The use of steroids (100%, P=.001) was the main risk factor in renal transplant patients. Skin lesions resolved in 60.7% (especially in those receiving multitargeted therapy). Patient survival at 12 months was 29% in transplant patients, 57% in haemodialysis patients and 100% in normal renal function patients (log-rank 6.88, P=.032). Chronic renal failure (P=.03) and hypoalbuminaemia (P=.02) were the main risk factor for CUA mortality. Although the incidence of CUA remains low, CUA mortality is very high, Special attention to its occurrence in kidney transplant patients and «non-renal» CUA forms is required. Oral anticoagulants and steroids appear to be the main risk factors, CUA is a challenge; a registry of patients and determining standard therapy are required. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Genomic analysis, cytokine expression, and microRNA profiling reveal biomarkers of human dietary zinc depletion and homeostasis.

PubMed

Ryu, Moon-Suhn; Langkamp-Henken, Bobbi; Chang, Shou-Mei; Shankar, Meena N; Cousins, Robert J

2011-12-27

Implementation of zinc interventions for subjects suspected of being zinc-deficient is a global need, but is limited due to the absence of reliable biomarkers. To discover molecular signatures of human zinc deficiency, a combination of transcriptome, cytokine, and microRNA analyses was applied to a dietary zinc depletion/repletion protocol with young male human subjects. Concomitant with a decrease in serum zinc concentration, changes in buccal and blood gene transcripts related to zinc homeostasis occurred with zinc depletion. Microarray analyses of whole blood RNA revealed zinc-responsive genes, particularly, those associated with cell cycle regulation and immunity. Responses of potential signature genes of dietary zinc depletion were further assessed by quantitative real-time PCR. The diagnostic properties of specific serum microRNAs for dietary zinc deficiency were identified by acute responses to zinc depletion, which were reversible by subsequent zinc repletion. Depression of immune-stimulated TNFα secretion by blood cells was observed after low zinc consumption and may serve as a functional biomarker. Our findings introduce numerous novel candidate biomarkers for dietary zinc status assessment using a variety of contemporary technologies and which identify changes that occur prior to or with greater sensitivity than the serum zinc concentration which represents the current zinc status assessment marker. In addition, the results of gene network analysis reveal potential clinical outcomes attributable to suboptimal zinc intake including immune function defects and predisposition to cancer. These demonstrate through a controlled depletion/repletion dietary protocol that the illusive zinc biomarker(s) can be identified and applied to assessment and intervention strategies.

The Motor Subsystem as a Predictor of Success in Young Football Talents: A Person-Oriented Study

PubMed Central

Zibung, Marc; Zuber, Claudia; Conzelmann, Achim

2016-01-01

Motor tests play a key role in talent selection in football. However, individual motor tests only focus on specific areas of a player’s complex performance. To evaluate his or her overall performance during a game, the current study takes a holistic perspective and uses a person-oriented approach. In this approach, several factors are viewed together as a system, whose state is analysed longitudinally. Based on this idea, six motor tests were aggregated to form the Motor Function subsystem. 104 young, top-level, male football talents were tested three times (2011, 2012, 2013; Mage, t2011 = 12.26, SD = 0.29), and their overall level of performance was determined one year later (2014). The data were analysed using the LICUR method, a pattern-analytical procedure for person-oriented approaches. At all three measuring points, four patterns could be identified, which remained stable over time. One of the patterns found at the third measuring point identified more subsequently successful players than random selection would. This pattern is characterised by above-average, but not necessarily the best, performance on the tests. Developmental paths along structurally stable patterns that occur more often than predicted by chance indicate that the Motor Function subsystem is a viable means of forecasting in the age range of 12–15 years. Above-average, though not necessary outstanding, performance both on fitness and technical tests appears to be particularly promising. These findings underscore the view that a holistic perspective may be profitable in talent selection. PMID:27508929

CA1 subfield contributions to memory integration and inference

PubMed Central

Schlichting, Margaret L.; Zeithamova, Dagmar; Preston, Alison R.

2014-01-01

The ability to combine information acquired at different times to make novel inferences is a powerful function of episodic memory. One perspective suggests that by retrieving related knowledge during new experiences, existing memories can be linked to the new, overlapping information as it is encoded. The resulting memory traces would thus incorporate content across event boundaries, representing important relationships among items encountered during separate experiences. While prior work suggests that the hippocampus is involved in linking memories experienced at different times, the involvement of specific subfields in this process remains unknown. Using both univariate and multivariate analyses of high-resolution functional magnetic resonance imaging (fMRI) data, we localized this specialized encoding mechanism to human CA1. Specifically, right CA1 responses during encoding of events that overlapped with prior experience predicted subsequent success on a test requiring inferences about the relationships among events. Furthermore, we employed neural pattern similarity analysis to show that patterns of activation evoked during overlapping event encoding were later reinstated in CA1 during successful inference. The reinstatement of CA1 patterns during inference was specific to those trials that were performed quickly and accurately, consistent with the notion that linking memories during learning facilitates novel judgments. These analyses provide converging evidence that CA1 plays a unique role in encoding overlapping events and highlight the dynamic interactions between hippocampal-mediated encoding and retrieval processes. More broadly, our data reflect the adaptive nature of episodic memories, in which representations are derived across events in anticipation of future judgments. PMID:24888442

Genetic distortion of the balance between punishment and relief learning in Drosophila.

PubMed

Yarali, Ayse; Krischke, Markus; Michels, Birgit; Saumweber, Timo; Mueller, Martin J; Gerber, Bertram

2009-01-01

An experience with electric shock can support two opposing kinds of behavioral effects: Stimuli that precede shock during training are subsequently avoided as predictors for punishment, whereas stimuli that follow shock during training are later on approached, as they predict relief. We show here, for the fruit fly Drosophila, that upon the loss of white-function, the balance between these two kinds of learning is distorted in favor of punishment learning: white1118 mutants show stronger punishment learning and weaker relief learning, as compared to wild type flies. Thus, white1118 mutants establish, overall, more "negative" memories for the shock experience. This only concerns the mnemonic effects of the shock; the immediate, reflexive responsiveness to shock remains unaltered. Also, learning about reward is apparently unaffected, both in adult and larval Drosophila. Prompted by the proposed function of the White protein as the transporter for biogenic amine precursors, we probed the brains of white1118 mutants for the amounts of biogenic amines (octopamine, tyramine, dopamine, and serotonin) by using high-pressure liquid chromatography coupled to mass spectrometry. Using this method, we found, however, no difference between white1118 and wild type files for any of the probed amines. In any event, analyses of how the white1118 mutation affects the balance between punishment and relief learning should provide a study case of how heritable distortions of such balance can come about. Finally, the effects of the white1118 mutation should be considered as a source of confound when using white as the "marker gene" in behavior-genetic analyses of any sort.

Impact of worsening renal function during the treatment of decompensated heart failure on changes in renal function during subsequent hospitalization.

PubMed

Testani, Jeffrey M; Cappola, Thomas P; McCauley, Brian D; Chen, Jennifer; Shen, James; Shannon, Richard P; Kimmel, Stephen E

2011-05-01

Worsening renal function (WRF) commonly complicates the treatment of acute decompensated heart failure. Despite considerable investigation in this area, it remains unclear to what degree WRF is a reflection of treatment- versus patient-related factors. We hypothesized that if WRF is significantly influenced by factors intrinsic to the patient, then WRF during an index hospitalization should predict WRF during subsequent hospitalization. Consecutive admissions to the Hospital of the University of Pennsylvania with a discharge diagnosis of congestive heart failure were reviewed. Patients with >1 hospitalization were retained for analysis. In total, 181 hospitalization pairs met the inclusion criteria. Baseline patient characteristics demonstrated significant correlation between hospitalizations (P ≤ .002 for all) but minimal association with WRF. In contrast, variables related to the aggressiveness of diuresis were weakly correlated between hospitalizations but significantly associated with WRF (P ≤ .024 for all). Consistent with the primary hypothesis, WRF during the index hospitalization was strongly associated with WRF during subsequent hospitalization (odds ratio [OR] 2.7, P = .003). This association was minimally altered after controlling for traditional baseline characteristics (OR 2.5, P = .006) and in-hospital treatment-related parameters (OR 2.8, P = .005). A prior history of WRF is strongly associated with subsequent episodes of WRF, independent of in-hospital treatment received. These results suggest that baseline factors intrinsic to the patient's cardiorenal pathophysiology have substantial influence on the subsequent development of WRF. Copyright © 2011 Mosby, Inc. All rights reserved.

Impact of Worsening Renal Function during the Treatment of Decompensated Heart Failure on Changes in Renal Function during Subsequent Hospitalization

PubMed Central

Testani, Jeffrey M.; Cappola, Thomas P.; McCauley, Brian D.; Chen, Jennifer; Shen, James; Shannon, Richard P.; Kimmel, Stephen E.

2011-01-01

Background Worsening renal function (WRF) commonly complicates the treatment of acute decompensated heart failure. Despite considerable investigation in this area, it remains unclear to what degree WRF is a reflection of treatment versus patient related factors. We hypothesized that if WRF is significantly influenced by factors intrinsic to the patient than WRF during an index hospitalization should predict WRF during subsequent hospitalization. Methods Consecutive admissions to the Hospital of the University of Pennsylvania with a discharge diagnosis of congestive heart failure were reviewed. Patients with >1 hospitalization were retained for analysis. Results In total 181 hospitalization pairs met the inclusion criteria. Baseline patient characteristics demonstrated significant correlation between hospitalizations (p≤0.002 for all) but minimal association with WRF. In contrast, variables related to the aggressiveness of diuresis were weakly correlated between hospitalizations but significantly associated with WRF (p≤0.024 for all). Consistent with the primary hypothesis, WRF during the index hospitalization was strongly associated with WRF during subsequent hospitalization (OR=2.7, p=0.003). This association was minimally altered after controlling for traditional baseline characteristics (OR=2.5, p=0.006) and in-hospital treatment related parameters (OR=2.8, p=0.005). Conclusions A prior history of WRF is strongly associated with subsequent episodes of WRF, independent of in-hospital treatment received. These results suggest that baseline factors intrinsic to the patient’s cardiorenal pathophysiology have substantial influence on the subsequent development of WRF. PMID:21570527

Association between intake of dairy products and short-term memory with and without adjustment for genetic and family environmental factors: A twin study.

PubMed

Ogata, Soshiro; Tanaka, Haruka; Omura, Kayoko; Honda, Chika; Hayakawa, Kazuo

2016-04-01

Previous studies have indicated associations between intake of dairy products and better cognitive function and reduced risk of dementia. However, these studies did not adjust for genetic and family environmental factors that may influence food intake, cognitive function, and metabolism of dairy product nutrients. In the present study, we investigated the association between intake of dairy products and short-term memory with and without adjustment for almost all genetic and family environmental factors using a genetically informative sample of twin pairs. A cross-sectional study was conducted among twin pairs aged between 20 and 74. Short-term memory was assessed as primary outcome variable, intake of dairy products was analyzed as the predictive variable, and sex, age, education level, marital status, current smoking status, body mass index, dietary alcohol intake, and medical history of hypertension or diabetes were included as possible covariates. Generalized estimating equations (GEE) were performed by treating twins as individuals and regression analyses were used to identify within-pair differences of a twin pair to adjust for genetic and family environmental factors. Data are reported as standardized coefficients and 95% confidence intervals (CI). Analyses were performed on data from 78 men and 278 women. Among men, high intake of dairy products was significantly associated with better short-term memory after adjustment for the possible covariates (standardized coefficients = 0.22; 95% CI, 0.06-0.38) and almost all genetic and family environmental factors (standardized coefficients = 0.38; 95% CI, 0.07-0.69). Among women, no significant associations were found between intake of dairy products and short-term memory. Subsequent sensitivity analyses were adjusted for small samples and showed similar results. Intake of dairy product may prevent cognitive declines regardless of genetic and family environmental factors in men. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Assessing the effect of elevated carbon dioxide on soil carbon: a comparison of four meta-analyses.

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

Hungate, B. A.; van Groenigen, K.; Six, J.

2009-08-01

Soil is the largest reservoir of organic carbon (C) in the terrestrial biosphere and soil C has a relatively long mean residence time. Rising atmospheric carbon dioxide (CO{sub 2}) concentrations generally increase plant growth and C input to soil, suggesting that soil might help mitigate atmospheric CO{sub 2} rise and global warming. But to what extent mitigation will occur is unclear. The large size of the soil C pool not only makes it a potential buffer against rising atmospheric CO{sub 2}, but also makes it difficult to measure changes amid the existing background. Meta-analysis is one tool that can overcomemore » the limited power of single studies. Four recent meta-analyses addressed this issue but reached somewhat different conclusions about the effect of elevated CO{sub 2} on soil C accumulation, especially regarding the role of nitrogen (N) inputs. Here, we assess the extent of differences between these conclusions and propose a new analysis of the data. The four meta-analyses included different studies, derived different effect size estimates from common studies, used different weighting functions and metrics of effect size, and used different approaches to address nonindependence of effect sizes. Although all factors influenced the mean effect size estimates and subsequent inferences, the approach to independence had the largest influence. We recommend that meta-analysts critically assess and report choices about effect size metrics and weighting functions, and criteria for study selection and independence. Such decisions need to be justified carefully because they affect the basis for inference. Our new analysis, with a combined data set, confirms that the effect of elevated CO{sub 2} on net soil C accumulation increases with the addition of N fertilizers. Although the effect at low N inputs was not significant, statistical power to detect biogeochemically important effect sizes at low N is limited, even with meta-analysis, suggesting the continued need for long-term experiments.« less

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer’s Disease or Mild Cognitive Impairment

PubMed Central

Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Gamble, Keith; Buchman, Aron S.; Bennett, David A.

2012-01-01

Objective Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment. Methods Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams. Results Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment). Conclusions Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment. PMID:22916287

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 differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences.

Dynamic functional connectivity analysis reveals transient states of dysconnectivity in schizophrenia

PubMed Central

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 differences are weak or absent during other connectivity states. Dynamic analysis also revealed hypoconnectivity between the putamen and sensory networks during the same states of thalamic hyperconnectivity; notably, this finding cannot be observed in the static connectivity analysis. Finally, in post-hoc analyses we observed that the relationships between sub-cortical low frequency power and connectivity with sensory networks is altered in patients, suggesting different functional interactions between sub-cortical nuclei and sensorimotor cortex during specific connectivity states. While important differences between patients with schizophrenia and healthy controls have been identified, one should interpret the results with caution given the history of medication in patients. Taken together, our results support and expand current knowledge regarding dysconnectivity in schizophrenia, and strongly advocate the use of dynamic analyses to better account for and understand functional connectivity differences. PMID:25161896

Aircraft Maneuvers for the Evaluation of Flying Qualities and Agility. Volume 1. Maneuver Development Process and Initial Maneuver Set

DTIC Science & Technology

1993-08-01

subtitled "Simulation Data," consists of detailed infonrnation on the design parmneter variations tested, subsequent statistical analyses conducted...used with confidence during the design process. The data quality can be examined in various forms such as statistical analyses of measure of merit data...merit, such as time to capture or nmaximurn pitch rate, can be calculated from the simulation time history data. Statistical techniques are then used

A novel bioinformatics pipeline to discover genes related to arbuscular mycorrhizal symbiosis based on their evolutionary conservation pattern among higher plants.

PubMed

Favre, Patrick; Bapaume, Laure; Bossolini, Eligio; Delorenzi, Mauro; Falquet, Laurent; Reinhardt, Didier

2014-12-03

Genes involved in arbuscular mycorrhizal (AM) symbiosis have been identified primarily by mutant screens, followed by identification of the mutated genes (forward genetics). In addition, a number of AM-related genes has been identified by their AM-related expression patterns, and their function has subsequently been elucidated by knock-down or knock-out approaches (reverse genetics). However, genes that are members of functionally redundant gene families, or genes that have a vital function and therefore result in lethal mutant phenotypes, are difficult to identify. If such genes are constitutively expressed and therefore escape differential expression analyses, they remain elusive. The goal of this study was to systematically search for AM-related genes with a bioinformatics strategy that is insensitive to these problems. The central element of our approach is based on the fact that many AM-related genes are conserved only among AM-competent species. Our approach involves genome-wide comparisons at the proteome level of AM-competent host species with non-mycorrhizal species. Using a clustering method we first established orthologous/paralogous relationships and subsequently identified protein clusters that contain members only of the AM-competent species. Proteins of these clusters were then analyzed in an extended set of 16 plant species and ranked based on their relatedness among AM-competent monocot and dicot species, relative to non-mycorrhizal species. In addition, we combined the information on the protein-coding sequence with gene expression data and with promoter analysis. As a result we present a list of yet uncharacterized proteins that show a strongly AM-related pattern of sequence conservation, indicating that the respective genes may have been under selection for a function in AM. Among the top candidates are three genes that encode a small family of similar receptor-like kinases that are related to the S-locus receptor kinases involved in sporophytic self-incompatibility. We present a new systematic strategy of gene discovery based on conservation of the protein-coding sequence that complements classical forward and reverse genetics. This strategy can be applied to diverse other biological phenomena if species with established genome sequences fall into distinguished groups that differ in a defined functional trait of interest.

Imbalance in Individual Researcher's Peer Review Activities Quantified for Four British Ecological Society Journals, 2003-2010

PubMed Central

Petchey, Owen L.; Fox, Jeremy W.; Haddon, Lindsay

2014-01-01

Researchers contribute to the scientific peer review system by providing reviews, and “withdraw” from it by submitting manuscripts that are subsequently reviewed. So far as we are aware, there has been no quantification of the balance of individual's contributions and withdrawals. We compared the number of reviews provided by individual researchers (i.e., their contribution) to the number required by their submissions (i.e. their withdrawals) in a large and anonymised database provided by the British Ecological Society. The database covered the Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and Functional Ecology from 2003–2010. The majority of researchers (64%) did not have balanced contributions and withdrawals. Depending on assumptions, 12% to 44% contributed more than twice as much as required; 20% to 52% contributed less than half as much as required. Balance, or lack thereof, varied little in relation to the number of years a researcher had been active (reviewing or submitting). Researchers who contributed less than required did not lack the opportunity to review. Researchers who submitted more were more likely to accept invitations to review. These finding suggest overall that peer review of the four analysed journals is not in crisis, but only due to the favourable balance of over- and under-contributing researchers. These findings are limited to the four journals analysed, and therefore cannot include researcher's other peer review activities, which if included might change the proportions reported. Relatively low effort was required to assemble, check, and analyse the data. Broader analyses of individual researcher's peer review activities would contribute to greater quality, efficiency, and fairness in the peer review system. PMID:24658631

Imbalance in individual researcher's peer review activities quantified for four British Ecological Society journals, 2003-2010.

PubMed

Petchey, Owen L; Fox, Jeremy W; Haddon, Lindsay

2014-01-01

Researchers contribute to the scientific peer review system by providing reviews, and "withdraw" from it by submitting manuscripts that are subsequently reviewed. So far as we are aware, there has been no quantification of the balance of individual's contributions and withdrawals. We compared the number of reviews provided by individual researchers (i.e., their contribution) to the number required by their submissions (i.e. their withdrawals) in a large and anonymised database provided by the British Ecological Society. The database covered the Journal of Ecology, Journal of Animal Ecology, Journal of Applied Ecology, and Functional Ecology from 2003-2010. The majority of researchers (64%) did not have balanced contributions and withdrawals. Depending on assumptions, 12% to 44% contributed more than twice as much as required; 20% to 52% contributed less than half as much as required. Balance, or lack thereof, varied little in relation to the number of years a researcher had been active (reviewing or submitting). Researchers who contributed less than required did not lack the opportunity to review. Researchers who submitted more were more likely to accept invitations to review. These finding suggest overall that peer review of the four analysed journals is not in crisis, but only due to the favourable balance of over- and under-contributing researchers. These findings are limited to the four journals analysed, and therefore cannot include researcher's other peer review activities, which if included might change the proportions reported. Relatively low effort was required to assemble, check, and analyse the data. Broader analyses of individual researcher's peer review activities would contribute to greater quality, efficiency, and fairness in the peer review system.

SeaWiFS Technical Report Series. Volume 38; SeaWiFS Calibration and Validation Quality Control Procedures

NASA Technical Reports Server (NTRS)

Hooker, Stanford B. (Editor); Firestone, Elaine R. (Editor); McClain, Charles R.; Darzi, Michael; Barnes, Robert A.; Eplee, Robert E.; Firestone, James K.; Patt, Frederick S.; Robinson, Wayne D.; Schieber, Brian D.;

Laboratory Protocol for Genetic Gut Content Analyses of Aquatic Macroinvertebrates Using Group-specific rDNA Primers.

PubMed

Koester, Meike; Gergs, René

2017-10-05

Analyzing food webs is essential for a better understanding of ecosystems. For example, food web interactions can undergo severe changes caused by the invasion of non-indigenous species. However, an exact identification of field predator-prey interactions is difficult in many cases. These analyses are often based on a visual evaluation of gut content or the analysis of stable isotope ratios (δ 15 N and δ 13 C). Such methods require comprehensive knowledge about, respectively, morphologic diversity or isotopic signature from individual prey organisms, leading to obstacles in the exact identification of prey organisms. Visual gut content analyses especially underestimate soft bodied prey organisms, because maceration, ingestion and digestion of prey organisms make identification of specific species difficult. Hence, polymerase chain reaction (PCR) based strategies, for example the use of group-specific primer sets, provide a powerful tool for the investigation of food web interactions. Here, we describe detailed protocols to investigate the gut contents of macroinvertebrate consumers from the field using group-specific primer sets for nuclear ribosomal deoxyribonucleic acid (rDNA). DNA can be extracted either from whole specimens (in the case of small taxa) or out of gut contents of specimens collected in the field. Presence and functional efficiency of the DNA templates need to be confirmed directly from the tested individual using universal primer sets targeting the respective subunit of DNA. We also demonstrate that consumed prey can be determined further down to species level via PCR with unmodified group-specific primers combined with subsequent single strand conformation polymorphism (SSCP) analyses using polyacrylamide gels. Furthermore, we show that the use of different fluorescent dyes as labels enables parallel screening for DNA fragments of different prey groups from multiple gut content samples via automated fragment analysis.

Player's success prediction in rugby union: From youth performance to senior level placing.

PubMed

Fontana, Federico Y; Colosio, Alessandro L; Da Lozzo, Giorgio; Pogliaghi, Silvia

2017-04-01

The study questioned if and to what extent specific anthropometric and functional characteristics measured in youth draft camps, can accurately predict subsequent career progression in rugby union. Original research. Anthropometric and functional characteristics of 531 male players (U16) were retrospectively analysed in relation to senior level team representation at age 21-24. Players were classified as International (Int: National team and international clubs) or National (Nat: 1st, 2nd and other divisions and dropout). Multivariate analysis of variance (one-way MANOVA) tested differences between Int and Nat, along a combination of anthropometric (body mass, height, body fat, fat-free mass) and functional variables (SJ, CMJ, t 15m , t 30m , VO 2max ). A discriminant function (DF) was determined to predict group assignment based on the linear combination of variables that best discriminate groups. Correct level assignment was expressed as % hit rate. A combination of anthropometric and functional characteristics reflects future level assignment (Int vs. Nat). Players' success can be accurately predicted (hit rate=81% and 77% for Int and Nat respectively) by a DF that combines anthropometric and functional variables as measured at ∼15 years of age, percent body fat and speed being the most influential predictors of group stratification. Within a group of 15 year-olds with exceptional physical characteristics, future players' success can be predicted using a linear combination of anthropometric and functional variables, among which a lower percent body fat and higher speed over a 15m sprint provide the most important predictors of the highest career success. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Nanosphere-based one-step strategy for efficient and nondestructive detection of circulating tumor cells.

PubMed

Wu, Ling-Ling; Wen, Cong-Ying; Hu, Jiao; Tang, Man; Qi, Chu-Bo; Li, Na; Liu, Cui; Chen, Lan; Pang, Dai-Wen; Zhang, Zhi-Ling

2017-08-15

Detecting viable circulating tumor cells (CTCs) without disruption to their functions for in vitro culture and functional study could unravel the biology of metastasis and promote the development of personalized anti-tumor therapies. However, existing CTC detection approaches commonly include CTC isolation and subsequent destructive identification, which damages CTC viability and functions and generates substantial CTC loss. To address the challenge of efficiently detecting viable CTCs for functional study, we develop a nanosphere-based cell-friendly one-step strategy. Immunonanospheres with prominent magnetic/fluorescence properties and extraordinary stability in complex matrices enable simultaneous efficient magnetic capture and specific fluorescence labeling of tumor cells directly in whole blood. The collected cells with fluorescent tags can be reliably identified, free of the tedious and destructive manipulations from conventional CTC identification. Hence, as few as 5 tumor cells in ca. 1mL of whole blood can be efficiently detected via only 20min incubation, and this strategy also shows good reproducibility with the relative standard deviation (RSD) of 8.7%. Moreover, due to the time-saving and gentle processing and the minimum disruption of immunonanospheres to cells, 93.8±0.1% of detected tumor cells retain cell viability and proliferation ability with negligible changes of cell functions, capacitating functional study on cell migration, invasion and glucose uptake. Additionally, this strategy exhibits successful CTC detection in 10/10 peripheral blood samples of cancer patients. Therefore, this nanosphere-based cell-friendly one-step strategy enables viable CTC detection and further functional analyses, which will help to unravel tumor metastasis and guide treatment selection. Copyright © 2017 Elsevier B.V. All rights reserved.

Traditional measures of normal anal sphincter function using high-resolution anorectal manometry (HRAM) in 115 healthy volunteers.

PubMed

Carrington, E V; Brokjaer, A; Craven, H; Zarate, N; Horrocks, E J; Palit, S; Jackson, W; Duthie, G S; Knowles, C H; Lunniss, P J; Scott, S M

2014-05-01

High-resolution anorectal manometry (HRAM) is a relatively new method for collection and interpretation of data relevant to sphincteric function, and for the first time allows a global appreciation of the anorectum as a functional unit. Historically, traditional anal manometry has been plagued by lack of standardization and healthy volunteer data of variable quality. The aims of this study were: (i) to obtain normative data sets for traditional measures of anorectal function using HRAM in healthy subjects and; (ii) to qualitatively describe novel physiological phenomena, which may be of future relevance when this method is applied to patients. 115 healthy subjects (96 female) underwent HRAM using a 10 channel, 12F solid-state catheter. Measurements were performed during rest, squeeze, cough, and simulated defecation (push). Data were displayed as color contour plots and analysed using a commercially available manometric system (Solar GI HRM v9.1, Medical Measurement Systems). Associations between age, gender and parity were subsequently explored. HRAM color contour plots provided clear delineation of the high-pressure zone within the anal canal and showed recruitment during maneuvers that altered intra-anal pressures. Automated analysis produced quantitative data, which have been presented on the basis of gender and parity due to the effect of these covariates on some sphincter functions. In line with traditional manometry, some age and gender differences were seen. Males had a greater functional anal canal length and anal pressures during the cough maneuver. Parity in females was associated with reduced squeeze increments. The study provides a large healthy volunteer dataset and parameters of traditional measures of anorectal function. A number of novel phenomena are appreciated, the significance of which will require further analysis and comparisons with patient populations. © 2014 John Wiley & Sons Ltd.

40 CFR 439.1 - General definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... a POTW treatment system to oxidize ammonia or ammonium salts initially to nitrites (via Nitrosomonas bacteria) and subsequently to nitrates (via Nitrobacter bacteria). Criteria for determining the... bacteria; and analyses of the nitrogen balance demonstrating a reduction in the concentration of ammonia or...

40 CFR 439.1 - General definitions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... a POTW treatment system to oxidize ammonia or ammonium salts initially to nitrites (via Nitrosomonas bacteria) and subsequently to nitrates (via Nitrobacter bacteria). Criteria for determining the... bacteria; and analyses of the nitrogen balance demonstrating a reduction in the concentration of ammonia or...

40 CFR 439.1 - General definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... a POTW treatment system to oxidize ammonia or ammonium salts initially to nitrites (via Nitrosomonas bacteria) and subsequently to nitrates (via Nitrobacter bacteria). Criteria for determining the... bacteria; and analyses of the nitrogen balance demonstrating a reduction in the concentration of ammonia or...

Global brain dynamics during social exclusion predict subsequent behavioral conformity

PubMed Central

Wasylyshyn, Nick; Hemenway Falk, Brett; Garcia, Javier O; Cascio, Christopher N; O’Donnell, Matthew Brook; Bingham, C Raymond; Simons-Morton, Bruce; Vettel, Jean M; Falk, Emily B

2018-01-01

Abstract Individuals react differently to social experiences; for example, people who are more sensitive to negative social experiences, such as being excluded, may be more likely to adapt their behavior to fit in with others. We examined whether functional brain connectivity during social exclusion in the fMRI scanner can be used to predict subsequent conformity to peer norms. Adolescent males (n = 57) completed a two-part study on teen driving risk: a social exclusion task (Cyberball) during an fMRI session and a subsequent driving simulator session in which they drove alone and in the presence of a peer who expressed risk-averse or risk-accepting driving norms. We computed the difference in functional connectivity between social exclusion and social inclusion from each node in the brain to nodes in two brain networks, one previously associated with mentalizing (medial prefrontal cortex, temporoparietal junction, precuneus, temporal poles) and another with social pain (dorsal anterior cingulate cortex, anterior insula). Using predictive modeling, this measure of global connectivity during exclusion predicted the extent of conformity to peer pressure during driving in the subsequent experimental session. These findings extend our understanding of how global neural dynamics guide social behavior, revealing functional network activity that captures individual differences. PMID:29529310

Tsunami Waves and Tsunami-Induced Natural Oscillations Determined by HF Radar in Ise Bay, Japan

NASA Astrophysics Data System (ADS)

Toguchi, Y.; Fujii, S.; Hinata, H.

2018-04-01

Tsunami waves and the subsequent natural oscillations generated by the 2011 Tohoku earthquake were observed by two high-frequency (HF) radars and four tidal gauge records in Ise Bay. The radial velocity components of both records increased abruptly at approximately 17:00 (JST) and continued for more than 24 h. This indicated that natural oscillations followed the tsunami in Ise Bay. The spectral analyses showed that the tsunami wave arrivals had periods of 16-19, 30-40, 60-90, and 120-140 min. The three longest periods were remarkably amplified. Time-frequency analysis also showed the energy increase and duration of these periods. We used an Empirical Orthogonal Function (EOF) to analyze the total velocity of the currents to find the underlying oscillation patterns in the three longest periods. To verify the physical properties of the EOF analysis results, we calculated the oscillation modes in Ise Bay using a numerical model proposed by Loomis. The results of EOF analysis showed that the oscillation modes of 120-140 and 60-90 min period bands were distributed widely, whereas the oscillation mode of the 30-40 min period band was distributed locally. The EOF spatial patterns of each period showed good agreement with the eigenmodes calculated by the method of Loomis (1975). Thus, the HF radars were capable of observing the tsunami arrival and the subsequent oscillations.

Spider Transcriptomes Identify Ancient Large-Scale Gene Duplication Event Potentially Important in Silk Gland Evolution

PubMed Central

Clarke, Thomas H.; Garb, Jessica E.; Hayashi, Cheryl Y.; Arensburger, Peter; Ayoub, Nadia A.

2015-01-01

The evolution of specialized tissues with novel functions, such as the silk synthesizing glands in spiders, is likely an influential driver of adaptive success. Large-scale gene duplication events and subsequent paralog divergence are thought to be required for generating evolutionary novelty. Such an event has been proposed for spiders, but not tested. We de novo assembled transcriptomes from three cobweb weaving spider species. Based on phylogenetic analyses of gene families with representatives from each of the three species, we found numerous duplication events indicative of a whole genome or segmental duplication. We estimated the age of the gene duplications relative to several speciation events within spiders and arachnids and found that the duplications likely occurred after the divergence of scorpions (order Scorpionida) and spiders (order Araneae), but before the divergence of the spider suborders Mygalomorphae and Araneomorphae, near the evolutionary origin of spider silk glands. Transcripts that are expressed exclusively or primarily within black widow silk glands are more likely to have a paralog descended from the ancient duplication event and have elevated amino acid replacement rates compared with other transcripts. Thus, an ancient large-scale gene duplication event within the spider lineage was likely an important source of molecular novelty during the evolution of silk gland-specific expression. This duplication event may have provided genetic material for subsequent silk gland diversification in the true spiders (Araneomorphae). PMID:26058392

Emotion regulation predicts symptoms of depression over five years.

PubMed

Berking, Matthias; Wirtz, Carolin M; Svaldi, Jennifer; Hofmann, Stefan G

2014-06-01

Deficits in emotion regulation have been identified as an important risk and maintaining factor for depression. The aim of this study was to examine the long-term effects of emotion regulation on symptoms of depression. Moreover, we investigated which specific emotion regulation skills were associated with subsequent symptoms of depression. Participants were 116 individuals (78% women, average age 35.2 years) who registered for an online-based assessment of depression and its risk-factors and reported at least some symptoms of depression. Successful application of emotion regulation skills and depressive symptom severity were assessed twice over a 5-year period. We utilized cross-lagged panel analyses to assess whether successful skills application would be negatively associated with subsequent depressive symptom severity. Cross-lagged panel analyses identified successful skills application as a significant predictor for depressive symptom severity even when controlling for the effects of initial symptoms of depression. A comparison of the effect sizes for different emotion regulation skills on subsequent depressive symptoms suggests that most of the skills included have similar predictive value. These findings provide preliminary evidence for the hypotheses that deficits in emotion regulation may contribute to the development of depression and that interventions systematically enhancing adaptive emotion regulation skills may help prevent and treat depressive symptoms. Copyright © 2014 Elsevier Ltd. All rights reserved.

Concept mapping as an approach for expert-guided model building: The example of health literacy.

PubMed

Soellner, Renate; Lenartz, Norbert; Rudinger, Georg

2017-02-01

Concept mapping served as the starting point for the aim of capturing the comprehensive structure of the construct of 'health literacy.' Ideas about health literacy were generated by 99 experts and resulted in 105 statements that were subsequently organized by 27 experts in an unstructured card sorting. Multidimensional scaling was applied to the sorting data and a two and three-dimensional solution was computed. The three dimensional solution was used in subsequent cluster analysis and resulted in a concept map of nine "clusters": (1) self-regulation, (2) self-perception, (3) proactive approach to health, (4) basic literacy and numeracy skills, (5) information appraisal, (6) information search, (7) health care system knowledge and acting, (8) communication and cooperation, and (9) beneficial personality traits. Subsequently, this concept map served as a starting point for developing a "qualitative" structural model of health literacy and a questionnaire for the measurement of health literacy. On the basis of questionnaire data, a "quantitative" structural model was created by first applying exploratory factor analyses (EFA) and then cross-validating the model with confirmatory factor analyses (CFA). Concept mapping proved to be a highly valuable tool for the process of model building up to translational research in the "real world". Copyright © 2016 Elsevier Ltd. All rights reserved.

The role of knee alignment in disease progression and functional decline in knee osteoarthritis.

PubMed

Sharma, L; Song, J; Felson, D T; Cahue, S; Shamiyeh, E; Dunlop, D D

2001-07-11

Knee osteoarthritis (OA) is a leading cause of disability in older persons. Few risk factors for disease progression or functional decline have been identified. Hip-knee-ankle alignment influences load distribution at the knee; varus and valgus alignment increase medial and lateral load, respectively. To test the hypotheses that (1) varus alignment increases risk of medial knee OA progression during the subsequent 18 months, (2) valgus alignment increases risk of subsequent lateral knee OA progression, (3) greater severity of malalignment is associated with greater subsequent loss of joint space, and (4) greater burden of malalignment is associated with greater subsequent decline in physical function. Prospective longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill. A total of 237 persons recruited from the community with primary knee OA, defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity; 230 (97%) completed the study. Progression of OA, defined as a 1-grade increase in severity of joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs; change in narrowest joint space width; and change in physical function between baseline and 18 months, compared by knee alignment at baseline. Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression, adjusting for age, sex, and body mass index (adjusted odds ratio [OR], 4.09; 95% confidence interval [CI], 2.20-7.62). Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression (adjusted OR, 4.89; 95% CI, 2.13-11.20). Severity of varus correlated with greater medial joint space loss during the subsequent 18 months (R = 0.52; 95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with greater subsequent lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47 in dominant knees). Having alignment of more than 5 degrees (in either direction) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees, after adjusting for age, sex, body mass index, and pain. This is, to our knowledge, the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increases risk of lateral OA progression, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.

Threonine-4 of mammalian RNA polymerase II CTD is targeted by Polo-like kinase 3 and required for transcriptional elongation

PubMed Central

Hintermair, Corinna; Heidemann, Martin; Koch, Frederic; Descostes, Nicolas; Gut, Marta; Gut, Ivo; Fenouil, Romain; Ferrier, Pierre; Flatley, Andrew; Kremmer, Elisabeth; Chapman, Rob D; Andrau, Jean-Christophe; Eick, Dirk

2012-01-01

Eukaryotic RNA polymerase II (Pol II) has evolved an array of heptad repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 at the carboxy-terminal domain (CTD) of the large subunit (Rpb1). Differential phosphorylation of Ser2, Ser5, and Ser7 in the 5′ and 3′ regions of genes coordinates the binding of transcription and RNA processing factors to the initiating and elongating polymerase complexes. Here, we report phosphorylation of Thr4 by Polo-like kinase 3 in mammalian cells. ChIPseq analyses indicate an increase of Thr4-P levels in the 3′ region of genes occurring subsequently to an increase of Ser2-P levels. A Thr4/Ala mutant of Pol II displays a lethal phenotype. This mutant reveals a global defect in RNA elongation, while initiation is largely unaffected. Since Thr4 replacement mutants are viable in yeast we conclude that this amino acid has evolved an essential function(s) in the CTD of Pol II for gene transcription in mammalian cells. PMID:22549466

Role of a heterotrimeric G-protein, Gi2, in the corticogenesis: possible involvement in periventricular nodular heterotopia and intellectual disability.

PubMed

Hamada, Nanako; Negishi, Yutaka; Mizuno, Makoto; Miya, Fuyuki; Hattori, Ayako; Okamoto, Nobuhiko; Kato, Mitsuhiro; Tsunoda, Tatsuhiko; Yamasaki, Mami; Kanemura, Yonehiro; Kosaki, Kenjiro; Tabata, Hidenori; Saitoh, Shinji; Nagata, Koh-Ichi

2017-01-01

We analyzed the role of a heterotrimeric G-protein, Gi2, in the development of the cerebral cortex. Acute knockdown of the α-subunit (Gαi2) with in utero electroporation caused delayed radial migration of excitatory neurons during corticogenesis, perhaps because of impaired morphology. The migration phenotype was rescued by an RNAi-resistant version of Gαi2. On the other hand, silencing of Gαi2 did not affect axon elongation, dendritic arbor formation or neurogenesis at ventricular zone in vivo. When behavior analyses were conducted with acute Gαi2-knockdown mice, they showed defects in social interaction, novelty recognition and active avoidance learning as well as increased anxiety. Subsequently, using whole-exome sequencing analysis, we identified a de novo heterozygous missense mutation (c.680C>T; p.Ala227Val) in the GNAI2 gene encoding Gαi2 in an individual with periventricular nodular heterotopia and intellectual disability. Collectively, the phenotypes in the knockdown experiments suggest a role of Gαi2 in the brain development, and impairment of its function might cause defects in neuronal functions which lead to neurodevelopmental disorders. © 2016 International Society for Neurochemistry.

Photoinduced electron transfer process on emission spectrum of N,N‧-bis(salicylidene)-1,2-phenylenediamine as a Mg2+ cation chemosensor: A first principle DFT and TDDFT study

NASA Astrophysics Data System (ADS)

Taherpour, Avat (Arman); Jamshidi, Morteza; Rezaei, Omid; Belverdi, Ali Rezaei

2018-06-01

The electronic and optical properties of N,N‧-bis(salicylidene)-1,2-phenylenediamine (SPDA) ligand were studied as a chemical sensor of Mg2+ cation in two solvents (water and DMSO) using the ab initio theory through Density Functional Theory (DFT) and Time Dependent Density Functional theory (TDDFT) methods. The results show that the SPDA ligand has a high ability for chemical sensing of Mg2+. The results has also represented that HOMO-LUMO energy gap decreases 0.941 eV after the complex formation between SPDA and Mg2+. In addition, obvious changes are found in the UV-Vis absorption spectrum, optical analyses SPDA ligand and [SPDA.Mg]2+ complex, which it has the capability of detecting Mg2+ via the adsorptive UV-Vis and colorimetric methods. Emission spectrum calculations and photoinduced electron transfer (PET) process in water solution shows different wavelength emission spectrum in amount of 4.6 nm. An analysis of NBO (natural bond orbital) data indicates tangible changes in the electron transfers data from the electron pairs of ligand to the conjugated system, both prior and subsequent to Mg2+addition.

Electro-mechanical vibration analysis of functionally graded piezoelectric porous plates in the translation state

NASA Astrophysics Data System (ADS)

Wang, Yan Qing

2018-02-01

To provide reference for aerospace structural design, electro-mechanical vibrations of functionally graded piezoelectric material (FGPM) plates carrying porosities in the translation state are investigated. A modified power law formulation is employed to depict the material properties of the plates in the thickness direction. Three terms of inertial forces are taken into account due to the translation of plates. The geometrical nonlinearity is considered by adopting the von Kármán non-linear relations. Using the d'Alembert's principle, the nonlinear governing equation of the out-of-plane motion of the plates is derived. The equation is further discretized to a system of ordinary differential equations using the Galerkin method, which are subsequently solved via the harmonic balance method. Then, the approximate analytical results are validated by utilizing the adaptive step-size fourth-order Runge-Kutta technique. Additionally, the stability of the steady state responses is examined by means of the perturbation technique. Linear and nonlinear vibration analyses are both carried out and results display some interesting dynamic phenomenon for translational porous FGPM plates. Parametric study shows that the vibration characteristics of the present inhomogeneous structure depend on several key physical parameters.

Carbon aerogels by pyrolysis of TEMPO-oxidized cellulose

NASA Astrophysics Data System (ADS)

Zhang, Sizhao; Feng, Jian; Feng, Junzong; Jiang, Yonggang; Ding, Feng

2018-05-01

Although carbon aerogels derived from naturally occurring materials have been developed extensively, a reasonable synthetic approach using cellulose-resource remains unclear. Here, we report a strategy to prepare carbon aerogels originated from cellulose position-selectively oxidized by TEMPO-oxidized process. Contrary to non-TEMPO-oxidized cellulose-derived carbon aerogels (NCCA) with relative loose structure, TEMPO-oxidized cellulose-derived carbon aerogels (TCCA) with tight fibrillar-continuous network are monitored, suggesting the importance of TEMPO-oxidized modification towards creating the architecture of subsequently produced carbon aerogels. TCCA endows a higher BET area despite owning slightly dense bulk density comparing with that of NCCA. The structural texture of TCCA could be maintained in a way in comparison to TEMPO-oxidized cellulose-derived aerogel, due to the integration and aggregation effect by losing the electric double layer repulsion via ionization of the surface carboxyl groups. FTIR and XPS analyses signify the evidence of non-functionalized carbon-skeleton network formation in terms of TCCA. Further, the mechanism concerning the creation of carbon aerogels is also established. These findings not only provide new insights into the production of carbon aerogels but also open up a new opportunity in the field of functional carbon materials.

Strain Effects in Epitaxial VO2 Thin Films on Columnar Buffer-Layer TiO2/Al2O3 Virtual Substrates.

PubMed

Breckenfeld, Eric; Kim, Heungsoo; Burgess, Katherine; Charipar, Nicholas; Cheng, Shu-Fan; Stroud, Rhonda; Piqué, Alberto

2017-01-18

Epitaxial VO 2 /TiO 2 thin film heterostructures were grown on (100) (m-cut) Al 2 O 3 substrates via pulsed laser deposition. We have demonstrated the ability to reduce the semiconductor-metal transition (SMT) temperature of VO 2 to ∼44 °C while retaining a 4 order of magnitude SMT using the TiO 2 buffer layer. A combination of electrical transport and X-ray diffraction reciprocal space mapping studies help examine the specific strain states of VO 2 /TiO 2 /Al 2 O 3 heterostructures as a function of TiO 2 film growth temperatures. Atomic force microscopy and transmission electron microscopy analyses show that the columnar microstructure present in TiO 2 buffer films is responsible for the partially strained VO 2 film behavior and subsequently favorable transport characteristics with a lower SMT temperature. Such findings are of crucial importance for both the technological implementation of the VO 2 system, where reduction of its SMT temperature is widely sought, as well as the broader complex oxide community, where greater understanding of the evolution of microstructure, strain, and functional properties is a high priority.

[The relation of workspace and installation space of epicyclic kinematics with six degrees of freedom].

PubMed

Pott, Peter P; Schwarz, Markus L R

2007-10-01

The kinematics of a robotic device significantly determines its installation space when it comes to technical realisation. With regard to the deployment of robotic manipulators in surgery, manipulators with a preferably small installation space are needed. This study describes six versions of novel epicyclic kinematics with six degrees of freedom (DOF). At first, the kinematics functionality was analysed using Gruebler's formula. Subsequently, the quantitative determination of the relation of workspace and installation space was performed using Matlab algorithms. To qualitatively describe the shape of the workspace, the Matlab visualisation features were utilised. For comparison, the well-known Hexapod was used. The assessed kinematics had 6-DOF-functionality. It became apparent that one version of the epicyclic kinematics having two 3-DOF disk systems mounted in a parallel way featured a particularly good relation of workspace and installation space. Compared to the Hexapod, this is approximately four times better. The shape of the workspaces of all epicyclic kinematics assessed was convex and compact. It could be shown that a novel epicyclic kinematics has a notably advantageous relation of workspace and installation space. Apparently, it seems to be well suited for the deployment in robotic machines for surgical procedures.

Sexually dimorphic traits in the silkworm, Bombyx mori, are regulated by doublesex.

PubMed

Xu, Jun; Zhan, Shuai; Chen, Shuqing; Zeng, Baosheng; Li, Zhiqian; James, Anthony A; Tan, Anjiang; Huang, Yongping

2017-01-01

The DM domain genes, doublesex (dsx) in insects, or their structural homologs, male abnormal 3 (mab-3) in nematodes and Dmrt1 (doublesex and mab-3-related transcription factor 1) in mammals, are downstream regulators of the sex determination pathway that control sexually dimorphic development. Despite the functional importance of dsx and its potential applications in sterile insect technologies (SITs), the mechanisms by which it controls sexually dimorphic traits and the subsequent developmental gene networks in insects are poorly understood. Phylogenetic analyses indicate that insect dsx genes have sex-specific alternative splicing isoforms, whereas other taxa do not. We exploited genome editing and transgenesis technologies to induce mutations in either the male-specific isoform (dsx M ) or common region (dsx C ) of dsx in the somatic tissues of the lepidopteran model insect Bombyx mori. Disruptions of gene function produced either male-specific sexually-dimorphic defects or intersexual phenotypes; these results differ from those observed in other insects, including Drosophila melanogaster. Our data provide insights into the divergence of the insect sex determination pathways related to the most conserved downstream component dsx. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of Effluent Irrigation on Community Composition and Function of Ammonia-Oxidizing Bacteria in Soil

PubMed Central

Oved, Tamar; Shaviv, Avi; Goldrath, Tal; Mandelbaum, Raphi T.; Minz, Dror

2001-01-01

The effect of effluent irrigation on community composition and function of ammonia-oxidizing bacteria (AOB) in soil was evaluated, using techniques of molecular biology and analytical soil chemistry. Analyses were conducted on soil sampled from lysimeters and from a grapefruit orchard which had been irrigated with wastewater effluent or fertilizer-amended water (FAW). Specifically, comparisons of AOB community composition were conducted using denaturing gradient gel electrophoresis (DGGE) of PCR-amplified fragments of the gene encoding the α-subunit of the ammonia monooxygenase gene (amoA) recovered from soil samples and subsequent sequencing of relevant bands. A significant and consistent shift in the population composition of AOB was detected in soil irrigated with effluent. This shift was absent in soils irrigated with FAW, despite the fact that the ammonium concentration in the FAW was similar. At the end of the irrigation period, Nitrosospira-like populations were dominant in soils irrigated with FAW, while Nitrosomonas-like populations were dominant in effluent-irrigated soils. Furthermore, DGGE analysis of the amoA gene proved to be a powerful tool in evaluating the soil AOB community population and population shifts therein. PMID:11472914

Epigenomic Reprogramming of Adult Cardiomyocyte-Derived Cardiac Progenitor Cells

PubMed Central

Zhang, Yiqiang; Zhong, Jiang F; Qiu, Hongyu; Robb MacLellan, W.; Marbán, Eduardo; Wang, Charles

2015-01-01

It has been believed that mammalian adult cardiomyocytes (ACMs) are terminally-differentiated and are unable to proliferate. Recently, using a bi-transgenic ACM fate mapping mouse model and an in vitro culture system, we demonstrated that adult mouse cardiomyocytes were able to dedifferentiate into cardiac progenitor-like cells (CPCs). However, little is known about the molecular basis of their intrinsic cellular plasticity. Here we integrate single-cell transcriptome and whole-genome DNA methylation analyses to unravel the molecular mechanisms underlying the dedifferentiation and cell cycle reentry of mouse ACMs. Compared to parental cardiomyocytes, dedifferentiated mouse cardiomyocyte-derived CPCs (mCPCs) display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlated well with the methylome, our transcriptomic data showed that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implantation of mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. Our study demonstrates that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. PMID:26657817

Finding the best density functional approximation to describe interaction energies and structures of ionic liquids in molecular dynamics studies

NASA Astrophysics Data System (ADS)

Perlt, Eva; Ray, Promit; Hansen, Andreas; Malberg, Friedrich; Grimme, Stefan; Kirchner, Barbara

2018-05-01

Ionic liquids raise interesting but complicated questions for theoretical investigations due to the fact that a number of different inter-molecular interactions, e.g., hydrogen bonding, long-range Coulomb interactions, and dispersion interactions, need to be described properly. Here, we present a detailed study on the ionic liquids ethylammonium nitrate and 1-ethyl-3-methylimidazolium acetate, in which we compare different dispersion corrected density functional approximations to accurate local coupled cluster data in static calculations on ionic liquid clusters. The efficient new composite method B97-3c is tested and has been implemented in CP2K for future studies. Furthermore, tight-binding based approaches which may be used in large scale simulations are assessed. Subsequently, ab initio as well as classical molecular dynamics simulations are conducted and structural analyses are presented in order to shed light on the different short- and long-range structural patterns depending on the method and the system size considered in the simulation. Our results indicate the presence of strong hydrogen bonds in ionic liquids as well as the aggregation of alkyl side chains due to dispersion interactions.

Using transportation accident databases to investigate ignition and explosion probabilities of flammable spills.

PubMed

Ronza, A; Vílchez, J A; Casal, J

2007-07-19

Risk assessment of hazardous material spill scenarios, and quantitative risk assessment in particular, make use of event trees to account for the possible outcomes of hazardous releases. Using event trees entails the definition of probabilities of occurrence for events such as spill ignition and blast formation. This study comprises an extensive analysis of ignition and explosion probability data proposed in previous work. Subsequently, the results of the survey of two vast US federal spill databases (HMIRS, by the Department of Transportation, and MINMOD, by the US Coast Guard) are reported and commented on. Some tens of thousands of records of hydrocarbon spills were analysed. The general pattern of statistical ignition and explosion probabilities as a function of the amount and the substance spilled is discussed. Equations are proposed based on statistical data that predict the ignition probability of hydrocarbon spills as a function of the amount and the substance spilled. Explosion probabilities are put forth as well. Two sets of probability data are proposed: it is suggested that figures deduced from HMIRS be used in land transportation risk assessment, and MINMOD results with maritime scenarios assessment. Results are discussed and compared with previous technical literature.

Anatomic and functional imaging of tagged molecules in animals

DOEpatents

Weisenberger, Andrew G [Yorktown, VA; Majewski, Stanislaw [Grafton, VA; Paulus, Michael J [Knoxville, TN; Gleason, Shaun S [Knoxville, VA

2007-04-24

A novel functional imaging system for use in the imaging of unrestrained and non-anesthetized small animals or other subjects and a method for acquiring such images and further registering them with anatomical X-ray images previously or subsequently acquired. The apparatus comprises a combination of an IR laser profilometry system and gamma, PET and/or SPECT, imaging system, all mounted on a rotating gantry, that permits simultaneous acquisition of positional and orientational information and functional images of an unrestrained subject that are registered, i.e. integrated, using image processing software to produce a functional image of the subject without the use of restraints or anesthesia. The functional image thus obtained can be registered with a previously or subsequently obtained X-ray CT image of the subject. The use of the system described herein permits functional imaging of a subject in an unrestrained/non-anesthetized condition thereby reducing the stress on the subject and eliminating any potential interference with the functional testing that such stress might induce.

Structural neural correlates of impaired mobility and subsequent decline in executive functions: A 12-month prospective study

PubMed Central

Hsu, Chun Liang; Best, John R.; Chiu, Bryan K.; Nagamatsu, Lindsay S; Voss, Michelle W.; Handy, Todd C.; Bolandzadeh, Niousha; Liu-Ambrose, Teresa

2016-01-01

Impaired mobility, such as falls, may be an early biomarker of subsequent cognitive decline and is associated with subclinical alterations in both brain structure and function. In this 12-month prospective study, we examined whether there are volumetric differences in gray matter and subcortical regions, as well as cerebral white matter, between older fallers and non-fallers. In addition, we assessed whether these baseline volumetric differences are associated with changes in cognitive function over 12 months. A total of 66 community-dwelling older adults were recruited and categorized by their falls status. Magnetic resonance imaging occurred at baseline and participants’ physical and cognitive performances were assessed at baseline and 12-months. At baseline, fallers showed significantly lower volumes in gray matter, subcortical regions, and cerebral white matter compared with non-fallers. Notably, fallers had significantly lower left lateral orbitofrontal white matter volume. Moreover, lower left lateral orbitofrontal white matter volume at baseline was associated with greater decline in set-shifting performance over 12 months. Our data suggest that falls may indicate subclinical alterations in regional brain volume that are associated with subsequent decline in executive functions. PMID:27079333

Preparation of water-soluble glycoconjugated poly(acrylamide) for NMR analyses of carbohydrate-carbohydrate interactions

NASA Astrophysics Data System (ADS)

Xuan, Trinh Anh; Trung, Phan Nghia; Dinh, Bui Long; Yamaguchi, Takumi; Kato, Koichi

2014-05-01

Oligosaccharide chains of glycoconjugates are important biopolymers not only as carriers of information in cell-cell interactions but also as markers of cellular differentiation, aging, and malignant alteration. Molecular interactions where carbohydrates are involved are usually considered as weak interactions, so the study and evaluation of these interactions is still in its infancy. The evidences and studies of carbohydrate-carbohydrate interactions (CCI) will be confirming the importance of this mechanism for specific cell adhesion and communication. Their development will go hand in hand with the development of new and more sensitive techniques to study weak interactions. Recently, synthetic glycopolymers with functions similar to those of such natural carbohydrates and with specific pendant saccharide moieties were used as a solution for enhancement CCI when forming polyvalent interactions. Carbohydrates are ubiquitous components of cell wall membranes and occur as glycolipids, glycoproteins, proteoglycans, and capsular polysaccharides. As such they can participate in forefront intramolecular and intracellular events. Apart from their recognized roles in the physicochemical properties of glycolipids and glycoproteins. In this study, we designed trisaccharide monomers for free radical polymerization. Subsequently, the trisaccharide unit for chemical conjugation was synthesized from galactosamine in good yield. For further NMR analyses of CCI, glycopolymers composed of these sugar derivatives will be provided.

Integration of GRACE and GNET GPS in modeling the deglaciation of Greenland

NASA Astrophysics Data System (ADS)

Knudsen, P.; Madsen, F. B.; Khan, S. A.; Bevis, M. G.; van Dam, T. M.

2017-12-01

The use the monthly gravity fields from the Gravity Recovery and Climate Experiment (GRACE) has become essential when assessing and modeling the mass changes of the ice sheets. The recent degradation of the current mission, however, has hampered the continuous monitoring of ice sheet masses, at least until GRACE Follow-On mission will become operational. Through the recent years it has been demonstrated that mass changes can be observed by GPS receivers mounted on the adjacent bedrock. Especially, the Greenland GPS Network (GNET) has proven that GPS is a valuable technique for detecting mass changes through the Earths elastic response. An integration of GNET with other observations of the Greenland ice sheet, e.g. satellite altimetry and GRACE, has made studies of GIA progressing significantly. In this study, we aim at improving the monitoring of the ice sheet mass by utilizing the redundancy for reducing the influence of errors and to fill in at data voids and, not at least to bridge the gap between GRACE and GRACE FO. Initial analyses are carried out to link GRACE and GNET time series empirically. EOF analyses are carried out to extract the main part of the variability and to isolate errors. Subsequently, empirical covariance functions are derived and used in the integration. Preliminary results are derived and inter-compared.

The interaction between the DRD4 VNTR polymorphism and perceived peer drinking norms in adolescent alcohol use and misuse

PubMed Central

Park, Aesoon; Kim, Jueun; Zaso, Michelle J.; Glatt, Stephen J.; Sher, Kenneth J.; Scott-Sheldon, Lori A. J.; Eckert, Tanya L.; Vanable, Peter A.; Carey, Kate B.; Ewart, Craig K.; Carey, Michael P.

2015-01-01

Peer drinking norms are arguably one of the strongest correlates of adolescent drinking. Prospective studies indicate that adolescents tend to select peers based on drinking (peer-selection) and their peers’ drinking is associated with changes in adolescent drinking over time (peer socialization). The present study investigated whether the peer selection and socialization processes in adolescent drinking differed as a function of the DRD4 VNTR genotype in two independent prospective datasets. The first sample was 174 high school students drawn from a 2-wave 6-month prospective study. The second sample was 237 college students drawn from a 3-wave annual prospective study. Multigroup cross-lagged panel analyses of the high school student sample indicated stronger socialization via peer drinking norms among carriers, whereas analyses of the college student sample indicated stronger drinking-based peer selection in the junior year among carriers, compared to non-carriers. Although replication and meta-analytic synthesis are needed, these findings suggest in part genetically determined peer-selection (carriers of the DRD4 7-repeat allele tend to associate with peers who have more favorable attitudes toward drinking and greater alcohol use) and peer socialization (carriers’ subsequent drinking behaviors are more strongly associated with their peer drinking norms) may differ across adolescent developmental stages. PMID:26902782

Effect of Measured Welding Residual Stresses on Crack Growth

NASA Technical Reports Server (NTRS)

Hampton, Roy W.; Nelson, Drew; Doty, Laura W. (Technical Monitor)

1998-01-01

Welding residual stresses in thin plate A516-70 steel and 2219-T87 aluminum butt weldments were measured by the strain-gage hole drilling and X-ray diffraction methods. The residual stress data were used to construct 3D strain fields which were modeled as thermally induced strains. These 3D strain fields were then analyzed with the WARP31) FEM fracture analysis code in order to predict their effect on fatigue and on fracture. For analyses of fatigue crack advance and subsequent verification testing, fatigue crack growth increments were simulated by successive saw-cuts and incremental loading to generate, as a function of crack length, effects on crack growth of the interaction between residual stresses and load induced stresses. The specimen experimental response was characterized and compared to the WARM linear elastic and elastic-plastic fracture mechanics analysis predictions. To perform the fracture analysis, the plate material's crack tearing resistance was determined by tests of thin plate M(T) specimens. Fracture analyses of these specimen were performed using WARP31D to determine the critical Crack Tip Opening Angle [CTOA] of each material. These critical CTOA values were used to predict crack tearing and fracture in the weldments. To verify the fracture predictions, weldment M(T) specimen were tested in monotonic loading to fracture while characterizing the fracture process.

Isolation and measurement of the features of arrays of cell aggregates formed by dielectrophoresis using the user-specified Multi Regions Masking (MRM) technique

NASA Astrophysics Data System (ADS)

Yusvana, Rama; Headon, Denis; Markx, Gerard H.

2009-08-01

The use of dielectrophoresis for the construction of artificial skin tissue with skin cells in follicle-like 3D cell aggregates in well-defined patterns is demonstrated. To analyse the patterns produced and to study their development after their formation a Virtual Instrument (VI) system was developed using the LabVIEW IMAQ Vision Development Module. A series of programming functions (algorithms) was used to isolate the features on the image (in our case; the patterned aggregates) and separate them from all other unwanted regions on the image. The image was subsequently converted into a binary version, covering only the desired microarray regions which could then be analysed by computer for automatic object measurements. The analysis utilized the simple and easy-to-use User-Specified Multi-Regions Masking (MRM) technique, which allows one to concentrate the analysis on the desired regions specified in the mask. This simplified the algorithms for the analysis of images of cell arrays having similar geometrical properties. By having a collection of scripts containing masks of different patterns, it was possible to quickly and efficiently develop sets of custom virtual instruments for the offline or online analysis of images of cell arrays in the database.

Generation and Characterization of Anti-CD34 Monoclonal Antibodies that React with Hematopoietic Stem Cells

PubMed Central

Aghebati Maleki, Leili; Majidi, Jafar; Baradaran, Behzad; Movassaghpour, Aliakbar; Abdolalizadeh, Jalal

2014-01-01

CD34 is a type I membrane protein with a molecular mass of approximately 110 kDa. This antigen is associated with human hematopoietic progenitor cells and is a differentiation stage-specific leukocyte antigen. In this study we have generated and characterized monoclonal antibodies (mAbs) directed against a CD34 marker. Mice were immunized with two keyhole lympet hemocyanin (KLH)-conjugated CD34 peptides. Fused cells were grown in hypoxanthine, aminopterine and thymidine (HAT) selective medium and cloned by the limiting dilution (L.D) method. Several monoclones were isolated by three rounds of limited dilutions. From these, we chose stable clones that presented sustained antibody production for subsequent characterization. Antibodies were tested for their reactivity and specificity to recognize the CD34 peptides and further screened by enzyme-linked immunosorbent assay (ELISA) and Western blotting analyses. One of the mAbs (3D5) was strongly reactive against the CD34 peptide and with native CD34 from human umbilical cord blood cells (UCB) in ELISA and Western blotting analyses. The results have shown that this antibody is highly specific and functional in biomedical applications such as ELISA and Western blot assays. This monoclonal antibodies (mAb) can be a useful tool for isolation and purification of human hematopoietic stem cells (HSCs). PMID:24611141

Hsf and Hsp gene families in Populus: genome-wide identification, organization and correlated expression during development and in stress responses.

PubMed

Zhang, Jin; Liu, Bobin; Li, Jianbo; Zhang, Li; Wang, Yan; Zheng, Huanquan; Lu, Mengzhu; Chen, Jun

2015-03-14

Heat shock proteins (Hsps) are molecular chaperones that are involved in many normal cellular processes and stress responses, and heat shock factors (Hsfs) are the transcriptional activators of Hsps. Hsfs and Hsps are widely coordinated in various biological processes. Although the roles of Hsfs and Hsps in stress responses have been well characterized in Arabidopsis, their roles in perennial woody species undergoing various environmental stresses remain unclear. Here, a comprehensive identification and analysis of Hsf and Hsp families in poplars is presented. In Populus trichocarpa, we identified 42 paralogous pairs, 66.7% resulting from a whole genome duplication. The gene structure and motif composition are relatively conserved in each subfamily. Microarray and quantitative real-time RT-PCR analyses showed that most of the Populus Hsf and Hsp genes are differentially expressed upon exposure to various stresses. A coexpression network between Populus Hsf and Hsp genes was generated based on their expression. Coordinated relationships were validated by transient overexpression and subsequent qPCR analyses. The comprehensive analysis indicates that different sets of PtHsps are downstream of particular PtHsfs and provides a basis for functional studies aimed at revealing the roles of these families in poplar development and stress responses.

An optimized transit peptide for effective targeting of diverse foreign proteins into chloroplasts in rice.

PubMed

Shen, Bo-Ran; Zhu, Cheng-Hua; Yao, Zhen; Cui, Li-Li; Zhang, Jian-Jun; Yang, Cheng-Wei; He, Zheng-Hui; Peng, Xin-Xiang

2017-04-11

Various chloroplast transit peptides (CTP) have been used to successfully target some foreign proteins into chloroplasts, but for other proteins these same CTPs have reduced localization efficiencies or fail completely. The underlying cause of the failures remains an open question, and more effective CTPs are needed. In this study, we initially observed that two E.coli enzymes, EcTSR and EcGCL, failed to be targeted into rice chloroplasts by the commonly-used rice rbcS transit peptide (rCTP) and were subsequently degraded. Further analyses revealed that the N-terminal unfolded region of cargo proteins is critical for their localization capability, and that a length of about 20 amino acids is required to attain the maximum localization efficiency. We considered that the unfolded region may alleviate the steric hindrance produced by the cargo protein, by functioning as a spacer to which cytosolic translocators can bind. Based on this inference, an optimized CTP, named RC2, was constructed. Analyses showed that RC2 can more effectively target diverse proteins, including EcTSR and EcGCL, into rice chloroplasts. Collectively, our results provide further insight into the mechanism of CTP-mediated chloroplastic localization, and more importantly, RC2 can be widely applied in future chloroplastic metabolic engineering, particularly for crop plants.

The Effect of Prior Concussion History on Dual-Task Gait following a Concussion.

PubMed

Howell, David R; Beasley, Michael; Vopat, Lisa; Meehan, William P

2017-02-15

Sustaining repeated concussions has been associated with worse outcomes after additional injuries. This effect has been identified using symptom inventories and neurocognitive tests; however, few investigations have examined how a prior concussion history affects gait soon after a subsequent concussion. We examined the gait characteristics of athletes with no documented concussion history (n = 31), athletes recovering from their first lifetime concussion (n = 15), and athletes recovering from their second or greater lifetime concussion (n = 22). All participants completed a single-task and dual-task gait examination, a medical history questionnaire, and a postconcussion symptom scale. Multivariate analyses of covariance (MANCOVA) models were used to evaluate mean gait differences among groups, and Spearman's ρ analyses were used to assess correlations between the number of lifetime concussions and gait characteristics. Patients reporting to the clinic with their second or greater lifetime concussion demonstrated smaller stride lengths than healthy control participants during dual-task walking (p = 0.01; d = 0.70). A moderate but insignificant correlation was detected between dual-task gait speed and the number of prior concussions (ρ = 0.41, p = 0.07). These results indicate that a cumulative effect of concussions across the lifetime may contribute to worsening dual-task dynamic motor function after concussion.

Correlation between TMD and Cervical Spine Pain and Mobility: Is the Whole Body Balance TMJ Related?

PubMed Central

Walczyńska-Dragon, Karolina; Baron, Stefan; Nitecka-Buchta, Aleksandra; Tkacz, Ewaryst

2014-01-01

Temporomandibular dysfunction (TMD) is considered to be associated with imbalance of the whole body. This study aimed to evaluate the influence of TMD therapy on cervical spine range of movement (ROM) and reduction of spinal pain. The study group consisted of 60 patients with TMD, cervical spine pain, and limited cervical spine range of movements. Subjects were interviewed by a questionnaire about symptoms of TMD and neck pain and had also masticatory motor system physically examined (according to RDC-TMD) and analysed by JMA ultrasound device. The cervical spine motion was analysed using an MCS device. Subjects were randomly admitted to two groups, treated and control. Patients from the treated group were treated with an occlusal splint. Patients from control group were ordered to self-control parafunctional habits. Subsequent examinations were planned in both groups 3 weeks and 3 months after treatment was introduced. The results of tests performed 3 months after the beginning of occlusal splint therapy showed a significant improvement in TMJ function (P > 0.05), cervical spine ROM, and a reduction of spinal pain. The conclusion is that there is a significant association between TMD treatment and reduction of cervical spine pain, as far as improvement of cervical spine mobility. PMID:25050363

Phosphorus saturation and superficial fertilizer application as key parameters to assess the risk of diffuse phosphorus losses from agricultural soils in Brazil.

PubMed

Fischer, P; Pöthig, R; Gücker, B; Venohr, M

2018-07-15

In Brazil, a steady increase in phosphorus (P) fertilizer application and agricultural intensification has been reported for recent decades. The concomitant P accumulation in soils potentially threatens surface water bodies with eutrophication through diffuse P losses. Here, we demonstrated the applicability of a soil type-independent approach for estimating the degree of P saturation (DPS; a risk parameter of P loss) by a standard method of water-soluble phosphorus (WSP) for two major soil types (Oxisols, Entisols) of the São Francisco catchment in Brazil. Subsequently, soil Mehlich-1P (M1P) levels recommended by Brazilian agricultural institutions were transformed into DPS values. Recommended M1P values for optimal agronomic production corresponded to DPS values below critical thresholds of high risks of P losses (DPS=80%) for major crops of the catchment. Higher risks of reaching critical DPS values due to P accumulation were found for Entisols due to their total sorption capacities being only half those of Oxisols. For complementary information on soil mineralogy and its influence on P sorption and P binding forms, Fourier transformation infrared (FTIR) spectroscopic analyses were executed. FTIR analyses suggested the occurrence of the clay minerals palygorskite and sepiolite in some of the analyzed Entisols and the formation of crandallite as the soil specific P binding form in the investigated Oxisols. Palygorskite and sepiolite can enhance P solubility and hence the risk of P losses. In contrast, the reshaping of superphosphate grains into crandallite may explain the chemical processes leading to previously observed low dissolved P concentrations in surface runoff from Oxisols. To prevent high risk of P losses, we recommend avoiding superficial fertilizer application and establishing environmental thresholds for soil M1P based on DPS. These measures could help to prevent eutrophication of naturally oligotrophic surface waters, and subsequent adverse effects on biodiversity and ecosystem function. Copyright © 2018 Elsevier B.V. All rights reserved.

Cognitive control, attention, and the other race effect in memory.

PubMed

Brown, Thackery I; Uncapher, Melina R; Chow, Tiffany E; Eberhardt, Jennifer L; Wagner, Anthony D

2017-01-01

People are better at remembering faces from their own race than other races-a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an "old/new" recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces.

Cognitive control, attention, and the other race effect in memory

PubMed Central

Uncapher, Melina R.; Chow, Tiffany E.; Eberhardt, Jennifer L.; Wagner, Anthony D.

2017-01-01

People are better at remembering faces from their own race than other races–a phenomenon with significant societal implications. This Other Race Effect (ORE) in memory could arise from different attentional allocation to, and cognitive control over, same- and other-race faces during encoding. Deeper or more differentiated processing of same-race faces could yield more robust representations of same- vs. other-race faces that could support better recognition memory. Conversely, to the extent that other-race faces may be characterized by lower perceptual expertise, attention and cognitive control may be more important for successful encoding of robust, distinct representations of these stimuli. We tested a mechanistic model in which successful encoding of same- and other-race faces, indexed by subsequent memory performance, is differentially predicted by (a) engagement of frontoparietal networks subserving top-down attention and cognitive control, and (b) interactions between frontoparietal networks and fusiform cortex face processing. European American (EA) and African American (AA) participants underwent fMRI while intentionally encoding EA and AA faces, and ~24 hrs later performed an “old/new” recognition memory task. Univariate analyses revealed greater engagement of frontoparietal top-down attention and cognitive control networks during encoding for same- vs. other-race faces, stemming particularly from a failure to engage the cognitive control network during processing of other-race faces that were subsequently forgotten. Psychophysiological interaction (PPI) analyses further revealed that OREs were characterized by greater functional interaction between medial intraparietal sulcus, a component of the top-down attention network, and fusiform cortex during same- than other-race face encoding. Together, these results suggest that group-based face memory biases at least partially stem from differential allocation of cognitive control and top-down attention during encoding, such that same-race memory benefits from elevated top-down attentional engagement with face processing regions; conversely, reduced recruitment of cognitive control circuitry appears more predictive of memory failure when encoding out-group faces. PMID:28282414

IQ and schizophrenia in a Swedish national sample: their causal relationship and the interaction of IQ with genetic risk.

PubMed

Kendler, Kenneth S; Ohlsson, Henrik; Sundquist, Jan; Sundquist, Kristina

2015-03-01

The authors sought to clarify the relationship between IQ and subsequent risk for schizophrenia. IQ was assessed at ages 18-20 in 1,204,983 Swedish males born between 1951 and 1975. Schizophrenia was assessed by hospital diagnosis through 2010. Cox proportional hazards models were used to investigate future risk for schizophrenia in individuals as a function of their IQ score, and then stratified models using pairs of relatives were used to adjust for familial cluster. Finally, regression models were used to examine the interaction between IQ and genetic liability on risk for schizophrenia. IQ had a monotonic relationship with schizophrenia risk across the IQ range, with a mean increase in risk of 3.8% per 1-point decrease in IQ; this association was stronger in the lower than the higher IQ range. Co-relative control analyses showed a similar association between IQ and schizophrenia in the general population and in cousin, half-sibling, and full-sibling pairs. A robust interaction was seen between genetic liability to schizophrenia and IQ in predicting schizophrenia risk. Genetic susceptibility for schizophrenia had a much stronger impact on risk of illness for those with low than high intelligence. The IQ-genetic liability interaction arose largely from IQ differences between close relatives. IQ assessed in late adolescence is a robust risk factor for subsequent onset of schizophrenia. This association is not the result of a declining IQ associated with insidious onset. In this large, representative sample, we found no evidence for a link between genius and schizophrenia. Co-relative control analyses showed that the association between lower IQ and schizophrenia is not the result of shared familial risk factors and may be causal. The strongest effect was seen with IQ differences within families. High intelligence substantially attenuates the impact of genetic liability on the risk for schizophrenia.

Self-rated health is associated with subsequent functional decline among older adults in Japan.

PubMed

Hirosaki, Mayumi; Okumiya, Kiyohito; Wada, Taizo; Ishine, Masayuki; Sakamoto, Ryota; Ishimoto, Yasuko; Kasahara, Yoriko; Kimura, Yumi; Fukutomi, Eriko; Chen, Wen Ling; Nakatsuka, Masahiro; Fujisawa, Michiko; Otsuka, Kuniaki; Matsubayashi, Kozo

2017-09-01

Previous studies have reported that self-rated health (SRH) predicts subsequent mortality. However, less is known about the association between SRH and functional ability. The aim of this study was to examine whether SRH predicts decline in basic activities of daily living (ADL), even after adjustment for depression, among community-dwelling older adults in Japan. A three-year prospective cohort study was conducted among 654 residents aged 65 years and older without disability in performing basic ADL at baseline. SRH was assessed using a visual analogue scale (range; 0-100), and dichotomized into low and high groups. Information on functional ability, sociodemographic factors, depressive symptoms, and medical conditions were obtained using a self-administered questionnaire. Logistic regression analysis was used to examine the association between baseline SRH and functional decline three years later. One hundred and eight (16.5%) participants reported a decline in basic ADL at the three-year follow-up. Multiple logistic regression analysis showed that the low SRH group had a higher risk for functional decline compared to the high SRH group, even after controlling for potential confounding factors (odds ratio (OR) = 2.4; 95% confidence interval (CI) = 1.3-4.4). Furthermore, a 10-point difference in SRH score was associated with subsequent functional decline (OR = 1.37; 95% CI = 1.16-1.61). SRH was an independent predictor of functional decline. SRH could be a simple assessment tool for predicting the loss or maintenance of functional ability in community-dwelling older adults. Positive self-evaluation might be useful to maintain an active lifestyle and stay healthy.

Cognition and objectively measured sleep duration in children: a systematic review and meta-analysis.

PubMed

Short, Michelle A; Blunden, Sarah; Rigney, Gabrielle; Matricciani, Lisa; Coussens, Scott; M Reynolds, Chelsea; Galland, Barbara

2018-06-01

Sleep recommendations are widely used to guide communities on children's sleep needs. Following recent adjustments to guidelines by the National Sleep Foundation and the subsequent consensus statement by the American Academy of Sleep Medicine, we undertook a systematic literature search to evaluate the current evidence regarding relationships between objectively measured sleep duration and cognitive function in children aged 5 to 13 years. Cognitive function included measures of memory, attention, processing speed, and intelligence in children aged 5 to 13 years. Keyword searches of 7 databases to December 2016 found 23 meeting inclusion criteria from 137 full articles reviewed, 19 of which were suitable for meta-analysis. A significant effect (r = .06) was found between sleep duration and cognition, suggesting that longer sleep durations were associated with better cognitive functioning. Analyses of different cognitive domains revealed that full/verbal IQ was significantly associated with sleep loss, but memory, fluid IQ, processing speed and attention were not. Comparison of study sleep durations with current sleep recommendations showed that most children studied had sleep durations that were not within the range of recommended sleep. As such, the true effect of sleep loss on cognitive function may be obscured in these samples, as most children were sleep restricted. Future research using more rigorous experimental methodologies is needed to properly elucidate the relationship between sleep duration and cognition in this age group. Copyright © 2018 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

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

Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.

2010-10-11

Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that lossmore » of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.« less

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series

PubMed Central

Fransson, Peter

2016-01-01

Abstract Assessment of dynamic functional brain connectivity based on functional magnetic resonance imaging (fMRI) data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transformation, which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is, however, unclear how well the stabilization of signal variance performed by the Fisher transformation works for each connectivity time series, when the true correlation is assumed to be fluctuating. This is of importance because many subsequent analyses either assume or perform better when the time series have stable variance or adheres to an approximate Gaussian distribution. In this article, using simulations and analysis of resting-state fMRI data, we analyze the effect of applying different variance stabilization strategies on connectivity time series. We focus our investigation on the Fisher transformation, the Box–Cox (BC) transformation and an approach that combines both transformations. Our results show that, if the intention of stabilizing the variance is to use metrics on the time series, where stable variance or a Gaussian distribution is desired (e.g., clustering), the Fisher transformation is not optimal and may even skew connectivity time series away from being Gaussian. Furthermore, we show that the suboptimal performance of the Fisher transformation can be substantially improved by including an additional BC transformation after the dynamic functional connectivity time series has been Fisher transformed. PMID:27784176

On Stabilizing the Variance of Dynamic Functional Brain Connectivity Time Series.

PubMed

Thompson, William Hedley; Fransson, Peter

2016-12-01

Assessment of dynamic functional brain connectivity based on functional magnetic resonance imaging (fMRI) data is an increasingly popular strategy to investigate temporal dynamics of the brain's large-scale network architecture. Current practice when deriving connectivity estimates over time is to use the Fisher transformation, which aims to stabilize the variance of correlation values that fluctuate around varying true correlation values. It is, however, unclear how well the stabilization of signal variance performed by the Fisher transformation works for each connectivity time series, when the true correlation is assumed to be fluctuating. This is of importance because many subsequent analyses either assume or perform better when the time series have stable variance or adheres to an approximate Gaussian distribution. In this article, using simulations and analysis of resting-state fMRI data, we analyze the effect of applying different variance stabilization strategies on connectivity time series. We focus our investigation on the Fisher transformation, the Box-Cox (BC) transformation and an approach that combines both transformations. Our results show that, if the intention of stabilizing the variance is to use metrics on the time series, where stable variance or a Gaussian distribution is desired (e.g., clustering), the Fisher transformation is not optimal and may even skew connectivity time series away from being Gaussian. Furthermore, we show that the suboptimal performance of the Fisher transformation can be substantially improved by including an additional BC transformation after the dynamic functional connectivity time series has been Fisher transformed.

Antioxidant multi-walled carbon nanotubes by free radical grafting of gallic acid: new materials for biomedical applications.

PubMed

Cirillo, Giuseppe; Hampel, Silke; Klingeler, Rüdiger; Puoci, Francesco; Iemma, Francesca; Curcio, Manuela; Parisi, Ortensia Ilaria; Spizzirri, Umile Gianfranco; Picci, Nevio; Leonhardt, Albrecht; Ritschel, Manfred; Büchner, Bernd

2011-02-01

To prove the possibility of covalently functionalizing multi-walled carbon nanotubes (CNTs) by free radical grafting of gallic acid on their surface with the subsequent synthesis of materials with improved biological properties evaluated by specific in-vitro assays. Antioxidant CNTs were synthesized by radical grafting of gallic acid onto pristine CNTs. The synthesis of carbon nanotubes was carried out in a fixed-bed reactor and, after the removal of the amorphous carbon, the grafting process was performed. The obtained materials were characterized by fluorescence and Fourier transform infrared spectroscopy (FT-IR) analyses. After assessment of the biocompatibility and determination of the disposable phenolic group content, the antioxidant properties were evaluated in terms of total antioxidant activity and scavenger ability against 2,2'-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl and peroxyl radicals. Finally the inhibition activity on acetylcholinesterase was evaluated.   The covalent functionalization of CNTs with gallic acid was confirmed and the amount of gallic acid bound per g of CNTs was found to be 2.1±0.2 mg. Good antioxidant and scavenging properties were recorded in the functionalized CNTs, which were found to be able to inhibit the acetylcholinesterase with potential improved activity for biomedical and pharmaceutical applications. For the first time, a free radical grafting procedure was proposed as a synthetic approach for the covalent functionalization of CNTs with an antioxidant polyphenol. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

Effect of breakfast on selected serum and cardiovascular variables

NASA Technical Reports Server (NTRS)

Frey, Mary A. B.; Merz, Marion P.; Hoffler, G. W.

1992-01-01

In view of the objections of many subjects to overnight fasting prior to their blood being drawn for analyses, the effect of eating breakfast on the results of subsequent blood analyses of selected blood constituents and on cardiovascular variables was investigated in 47 men and 34 women who were subjected to blood analyses on two occasions, one week apart: once fasting and once after breakfast. Results suggest that subjects need not fast overnight before blood is being drawn for determinations of the HDL-C levels, hemoglobin, hematocrit, total cholesterol, or phosphorus. However, based on other studies, it is suggested breakfast should not have a high content of fat.

Employability Deconstructed: Perceptions of Bologna Stakeholders

ERIC Educational Resources Information Center

Sin, Cristina; Neave, Guy

2016-01-01

The paper analyses employability as a floating signifier--a construct that accommodates different and often contending meanings. A preliminary analysis of scholarly literature identifies two opposed interpretations of employability--an individual responsibility versus a comprehensive context-aware construct. These are subsequently applied to the…

Reinforcement and validation of the analyses and conclusions related to fishway evaluation data from Bunt et al.: ‘Performance of fish passage structures at upstream barriers to migration’

USGS Publications Warehouse

Bunt, C.M.; Castro-Santos, Theodore R.; Haro, Alexander

2016-01-01

Detailed re-examination of the datasets that were used for a meta-analysis of fishway attraction and passage revealed a number of errors that we addressed and corrected. We subsequently re-analysed the revised dataset, and results showed no significant changes in the primary conclusions of the original study; for most species, effective performance cannot be assured for any fishway type.

Doping Level of Boron-Doped Diamond Electrodes Controls the Grafting Density of Functional Groups for DNA Assays.

PubMed

Švorc, Ĺubomír; Jambrec, Daliborka; Vojs, Marian; Barwe, Stefan; Clausmeyer, Jan; Michniak, Pavol; Marton, Marián; Schuhmann, Wolfgang

2015-09-02

The impact of different doping levels of boron-doped diamond on the surface functionalization was investigated by means of electrochemical reduction of aryldiazonium salts. The grafting efficiency of 4-nitrophenyl groups increased with the boron levels (B/C ratio from 0 to 20,000 ppm). Controlled grafting of nitrophenyldiazonium was used to adjust the amount of immobilized single-stranded DNA strands at the surface and further on the hybridization yield in dependence on the boron doping level. The grafted nitro functions were electrochemically reduced to the amine moieties. Subsequent functionalization with a succinic acid introduced carboxyl groups for subsequent binding of an amino-terminated DNA probe. DNA hybridization significantly depends on the probe density which is in turn dependent on the boron doping level. The proposed approach opens new insights for the design and control of doped diamond surface functionalization for the construction of DNA hybridization assays.

Cognitive functioning and insight in schizophrenia and in schizoaffective disorder.

PubMed

Birindelli, Nadia; Montemagni, Cristiana; Crivelli, Barbara; Bava, Irene; Mancini, Irene; Rocca, Paola

2014-01-01

The aim of this study was to investigate cognitive functioning and insight of illness in two groups of patients during their stable phases, one with schizophrenia and one with schizoaffective disorder. We recruited 104 consecutive outpatients, 64 with schizophrenia, 40 with schizoaffective disorder, in the period between July 2010 and July 2011. They all fulfilled formal Diagnostic and Statistical Manual of Mental disorders (DSM-IV-TR) diagnostic criteria for schizophrenia and schizoaffective disorder. Psychiatric assessment included the Clinical Global Impression Scale-Severity (CGI-S), the Positive and Negative Sindrome Scale (PANSS), the Calgary Depression Scale for Schizophrenia (CDSS) and the Global Assessment of Functioning (GAF). Insight of illness was evaluated using SUMD. Neuropsychological assessment included Winsconsin Card Sorting Test (WCST), California Verbal Learning Test (CVLT), Stroop Test and Trail Making Test (TMT). Differences between the groups were tested using Chi-square test for categorical variables and one-way analysis of variance (ANOVA) for continuous variables. All variables significantly different between the two groups of subjects were subsequently analysed using a logistic regression with a backward stepwise procedure using diagnosis (schizophrenia/schizoaffective disorder) as dependent variable. After backward selection of variables, four variables predicted a schizoaffective disorder diagnosis: marital status, a higher number of admission, better attentive functions and awareness of specific signs or symptoms of disease. The prediction model accounted for 55% of the variance of schizoaffective disorder diagnosis. With replication, our findings would allow higher diagnostic accuracy and have an impact on clinical decision making, in light of an amelioration of vocational functioning.

A high-throughput single-cell analysis of human CD8+ T cell functions reveals discordance for cytokine secretion and cytolysis

PubMed Central

Varadarajan, Navin; Julg, Boris; Yamanaka, Yvonne J.; Chen, Huabiao; Ogunniyi, Adebola O.; McAndrew, Elizabeth; Porter, Lindsay C.; Piechocka-Trocha, Alicja; Hill, Brenna J.; Douek, Daniel C.; Pereyra, Florencia; Walker, Bruce D.; Love, J. Christopher

2011-01-01

CD8+ T cells are a key component of the adaptive immune response to viral infection. An inadequate CD8+ T cell response is thought to be partly responsible for the persistent chronic infection that arises following infection with HIV. It is therefore critical to identify ways to define what constitutes an adequate or inadequate response. IFN-γ production has been used as a measure of T cell function, but the relationship between cytokine production and the ability of a cell to lyse virus-infected cells is not clear. Moreover, the ability to assess multiple CD8+ T cell functions with single-cell resolution using freshly isolated blood samples, and subsequently to recover these cells for further functional analyses, has not been achieved. As described here, to address this need, we have developed a high-throughput, automated assay in 125-pl microwells to simultaneously evaluate the ability of thousands of individual CD8+ T cells from HIV-infected patients to mediate lysis and to produce cytokines. This concurrent, direct analysis enabled us to investigate the correlation between immediate cytotoxic activity and short-term cytokine secretion. The majority of in vivo primed, circulating HIV-specific CD8+ T cells were discordant for cytolysis and cytokine secretion, notably IFN-γ, when encountering cognate antigen presented on defined numbers of cells. Our approach should facilitate determination of signatures of functional variance among individual effector CD8+ T cells, including those from mucosal samples and those induced by vaccines. PMID:21965332

Mediating pathways and gender differences between shift work and subjective cognitive function.

PubMed

Wong, Imelda S; Smith, Peter M; Ibrahim, Selahadin; Mustard, Cameron A; Gignac, Monique A M

2016-11-01

Increased injury risk among shift workers is often attributed to cognitive function deficits that come about as a result of sleep disruptions. However, little is known about the intermediate influences of other factors (eg, work stress, health) which may affect this relationship. In addition, gender differences in these the complex relationships have not been fully explored. The purpose of this study is to (1) identify the extent to which work and non-work factors mediate the relationship between shift work, sleep and subsequent subjective cognitive function; and (2) determine if the mediating pathways differ for men and women. Data from the 2010 National Population Health Survey was used to create a cross-sectional sample of 4255 employed Canadians. Using path modelling, we examined the direct and indirect relationships between shift work, sleep duration, sleep quality and subjective cognitive function. Multigroup analyses tested for significantly different pathways between men and women. Potential confounding effects of age and self-reported health and potential mediating effects of work stress were simultaneously examined. Work stress and sleep quality significantly mediated the effects of shift work on cognition. Age and health confounded the relationship between sleep quality and subjective cognition. No differences were found between men and women. Occupational health and safety programmes are needed to address stress and health factors, in addition to sleep hygiene, to effectively address cognitive function among shift workers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Improvements in hip flexibility do not transfer to mobility in functional movement patterns.

PubMed

Moreside, Janice M; McGill, Stuart M

2013-10-01

The purpose of this study was to analyze the transference of increased passive hip range of motion (ROM) and core endurance to functional movement. Twenty-four healthy young men with limited hip mobility were randomly assigned to 4 intervention groups: group 1, stretching; group 2, stretching plus hip/spine disassociation exercises; group 3, core endurance; and group 4, control. Previous work has documented the large increase in passive ROM and core endurance that was attained over the 6-week interventions, but whether these changes transferred to functional activities was unclear. Four dynamic activities were analyzed before and after the 6-week interventions: active standing hip extension, lunge, a standing twist/reach maneuver, and exercising on an elliptical trainer. A Vicon motion capture system collected body segment kinematics, with hip and lumbar spine angles subsequently calculated in Visual 3D. Repeated measures analyses of variance determined group effects on various hip and spine angles, with paired t-tests on specific pre/post pairs. Despite the large increases in passive hip ROM, there was no evidence of increased hip ROM used during functional movement testing. Similarly, the only significant change in lumbar motion was a reduction in lumbar rotation during the active hip extension maneuver (p < 0.05). These results indicate that changes in passive ROM or core endurance do not automatically transfer to changes in functional movement patterns. This implies that training and rehabilitation programs may benefit from an additional focus on 'grooving' new motor patterns if newfound movement range is to be used.

Training Residential Staff to Conduct Trial-Based Functional Analyses

ERIC Educational Resources Information Center

Lambert, Joseph M.; Bloom, Sarah E.; Kunnavatana, S. Shanun; Collins, Shawnee D.; Clay, Casey J.

2013-01-01

We taught 6 supervisors of a residential service provider for adults with developmental disabilities to train 9 house managers to conduct trial-based functional analyses. Effects of the training were evaluated with a nonconcurrent multiple baseline. Results suggest that house managers can be trained to conduct trial-based functional analyses with…

Prediction of the fate of p,p'-DDE in sediment on the Palos Verdes shelf, California, USA

USGS Publications Warehouse

Sherwood, C.R.; Drake, D.E.; Wiberg, P.L.; Wheatcroft, R.A.

2002-01-01

Long-term (60-yr) predictions of vertical profiles of p,p???-DDE concentrations in contaminated bottom sediments on the Palos Verdes shelf were calculated for three locations along the 60-m isobath using a numerical solution of the one-dimensional advection-diffusion equation. The calculations incorporated the following processes: sediment deposition (or erosion), depth-dependent solid-phase biodiffusive mixing, in situ diagenetic transformation, and loss of p,p???-DDE across the sediment-water interface by two mechanisms (resuspension of sediments by wave action and subsequent loss of p,p???-DDE to the water column by desorption, and desorption from sediments to porewater and subsequent molecular diffusion to the water column). A combination of field measurements, laboratory analyses, and calculations with supporting models was used to set parameters for the model. The model explains significant features observed in measurements made every 2 years from 1981 to 1997 by the County Sanitation Districts of Los Angeles (LACSD). Analyses of available data suggest that two sites northwest of the Whites Point sewage outfalls will remain depositional, even as particulate supply from the sewage-treatment plant and nearby Portuguese Bend Landslide decreases. At these sites, model predictions for 1991-2050 indicate that most of the existing inventory of p,p???-DDE will remain buried and that surface concentrations will gradually decrease. Analyses of data southeast of the outfalls suggest that erosion is likely to occur somewhere on the southeast edge of the existing effluent-affected deposit, and model predictions for such a site showed that erosion and biodiffusion will reintroduce the p,p???-DDE to the upper layer of sediments, with subsequent increases in surface concentrations and loss to the overlying water column.

Examining the link between women's exposure to stressful life events prior to conception and infant and toddler health: the role of birth weight.

PubMed

Cheng, Erika R; Park, Hyojun; Wisk, Lauren E; Mandell, Kara C; Wakeel, Fathima; Litzelman, Kristin; Chatterjee, Debanjana; Witt, Whitney P

2016-03-01

The life course perspective suggests a pathway may exist among maternal exposure to stressful life events prior to conception (PSLEs), infant birth weight and subsequent offspring health, whereby PSLEs are part of a 'chains-of-risk' that set children on a certain health pathway. No prior study has examined the link between PSLEs and offspring health in a nationally representative sample of US mothers and their children. We used longitudinal, nationally representative data to evaluate the relation between maternal exposure to PSLEs and subsequent measures of infant and toddler health, taking both maternal and obstetric characteristics into account. We examined 6900 mother-child dyads participating in 2 waves of the nationally representative Early Childhood Longitudinal Study-Birth Cohort (n=6900). Infant and toddler health outcomes assessed at 9 and 24 months included overall health status, special healthcare needs and severe health conditions. Adjusted path analyses examined associations between PSLEs, birth weight and child health outcomes. In adjusted analyses, PSLEs increased the risk for very low birth weight (VLBW, <1500 g), which, in turn, predicted poor health at both 9 and 24 months of age. Path analyses demonstrated that PSLEs had small indirect effects on children's subsequent health that operated through VLBW. Our analysis suggests a chains-of-risk model in which women's exposure to PSLEs increases the risk for giving birth to a VLBW infant, which, in turn, adversely affects infant and toddler health. Addressing women's preconception health may have important downstream benefits for their children, although more research is needed to replicate these findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Examining the link between women’s exposure to stressful life events prior to conception and infant and toddler health: The role of birthweight

PubMed Central

Cheng, Erika R.; Park, Hyojun; Wisk, Lauren E.; Mandell, Kara C.; Wakeel, Fathima; Litzelman, Kristin; Chatterjee, Debanjana; Witt, Whitney P.

2015-01-01

Background The lifecourse perspective suggests a pathway may exist among maternal exposure to stressful life events prior to conception (PSLEs), infant birthweight, and subsequent offspring health, whereby PLSEs are part of a “chains-of-risk” that set children on a certain health pathway. No prior study has examined the link between PSLEs and offspring health in a nationally-representative sample of US mothers and their children. We used longitudinal, nationally-representative data to evaluate the relation between maternal exposure to PSLEs and subsequent measures of infant and toddler health, taking both maternal and obstetric characteristics into account. Methods We examined 6,900 mother-child dyads participating in two waves of the nationally-representative Early Childhood Longitudinal Study-Birth Cohort (n=6,900). Infant and toddler health outcomes assessed at 9 and 24 months included overall health status, special health care needs, and severe health conditions. Adjusted path analyses examined associations between PSLEs, birthweight, and child health outcomes. Results In adjusted analyses, PSLEs increased the risk for very low birthweight (VLBW, <1,500 grams), which, in turn, predicted poor health at both 9 and 24 months of age. Path analyses demonstrated that PSLEs had small indirect effects on children’s subsequent health that operated through VLBW. Conclusion Our analysis suggests a chains-of-risk model in which women’s exposure to PSLEs increases the risk for giving birth to a VLBW infant, which, in turn, adversely affects infant and toddler health. Addressing women’s preconception health may have important downstream benefits for their children, although more research is needed to replicate these findings. PMID:26500337

Intervention to prevent further falls in older people who call an ambulance as a result of a fall: a protocol for the iPREFER randomised controlled trial.

PubMed

Mikolaizak, A Stefanie; Simpson, Paul M; Tiedemann, Anne; Lord, Stephen R; Caplan, Gideon A; Bendall, Jason C; Howard, Kirsten; Close, Jacqueline C T

2013-09-27

An increasing number of falls result in an emergency call and the subsequent dispatch of paramedics. In the absence of physical injury, abnormal physiological parameters or change in usual functional status, it could be argued that routine conveyance by ambulance to the Emergency Department (ED) is not the most effective or efficient use of resources. Further, it is likely that non-conveyed older fallers have the potential to benefit from timely access to fall risk assessment and intervention. The aim of this randomised controlled trial is to evaluate the effect of a timely and tailored falls assessment and management intervention on the number of subsequent falls and fall-related injuries for non-conveyed older fallers. Community dwelling people aged 65 years or older who are not conveyed to the ED following a fall will be eligible to be visited at home by a research physiotherapist. Consenting participants will receive individualised intervention strategies based on risk factors identified at baseline. All pre-test measures will be assessed prior to randomisation. Post-test measures will be undertaken by a researcher blinded to group allocation 6 months post-baseline. Participants in the intervention group will receive individualised pro-active fall prevention strategies from the clinical researcher to ensure that risk factors are addressed adequately and interventions carried out. The primary outcome measure will be the number of falls recorded by a falls diary over a 12 month period. Secondary outcome measures assessed six months after baseline will include the subsequent use of medical and emergency services and uptake of recommendations. Data will be analysed using the intention-to-treat principle. As there is currently little evidence regarding the effectiveness or feasibility of alternate models of care following ambulance non-conveyance of older fallers, there is a need to explore assessment and intervention programs to help reduce subsequent falls, related injuries and subsequent use of health care services. By linking existing services rather than setting up new services, this pragmatic trial aims to utilise the health care system in an efficient and timely manner. Australian New Zealand Clinical Trials Registry: ACTRN 12611000503921.

Symptoms of depression and anxiety as predictors of physical functioning in breast cancer patients. A prospective study using path analysis.

PubMed

Faller, Hermann; Strahl, André; Richard, Matthias; Niehues, Christiane; Meng, Karin

2017-12-01

Although symptoms of depression and anxiety are linked to health-related quality of life (HRQoL), the nature of this relationship remained unclear. We therefore aimed to examine, in a prospective study, both possible directions of impact in this relationship. To avoid conceptual and measurement overlap between depressive and anxiety symptoms, on the one hand, and HRQoL, on the other hand, we focused on the physical functioning component of HRQoL. We conducted a secondary analysis of a prospective cohort study with 436 female breast cancer patients (mean age 51 years). Both at baseline and after 12 months, we measured symptoms of depression and anxiety with the four-item Patient Heath Questionnaire (PHQ-4) and physical functioning with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30). Using path analysis, we estimated (1) the predictive value of symptoms of depression/anxiety for subsequent physical functioning and (2) the predictive value of physical functioning for subsequent symptoms of depression/anxiety, in the same model. Baseline symptoms of depression/anxiety predicted 1-year levels of physical functioning (depression: standardized β =  -.09, p = .024; anxiety: standardized β =  -.10, p = .009), while the reciprocal paths linking baseline physical functioning to subsequent depressive and anxiety symptoms were not significant, adjusting for the baseline scores of all outcome variables. Depressive and anxiety symptoms were predictors of the physical functioning component of HRQoL. Thus, if this relation is causal, treating breast cancer patients' depressive and anxiety symptoms may have a favorable impact on their self-reported physical functioning.

Prediction of recovery of motor function after stroke.

PubMed

Stinear, Cathy

2010-12-01

Stroke is a leading cause of disability. The ability to live independently after stroke depends largely on the reduction of motor impairment and the recovery of motor function. Accurate prediction of motor recovery assists rehabilitation planning and supports realistic goal setting by clinicians and patients. Initial impairment is negatively related to degree of recovery, but inter-individual variability makes accurate prediction difficult. Neuroimaging and neurophysiological assessments can be used to measure the extent of stroke damage to the motor system and predict subsequent recovery of function, but these techniques are not yet used routinely. The use of motor impairment scores and neuroimaging has been refined by two recent studies in which these investigations were used at multiple time points early after stroke. Voluntary finger extension and shoulder abduction within 5 days of stroke predicted subsequent recovery of upper-limb function. Diffusion-weighted imaging within 7 days detected the effects of stroke on caudal motor pathways and was predictive of lasting motor impairment. Thus, investigations done soon after stroke had good prognostic value. The potential prognostic value of cortical activation and neural plasticity has been explored for the first time by two recent studies. Functional MRI detected a pattern of cortical activation at the acute stage that was related to subsequent reduction in motor impairment. Transcranial magnetic stimulation enabled measurement of neural plasticity in the primary motor cortex, which was related to subsequent disability. These studies open interesting new lines of enquiry. WHERE NEXT?: The accuracy of prediction might be increased by taking into account the motor system's capacity for functional reorganisation in response to therapy, in addition to the extent of stroke-related damage. Improved prognostic accuracy could also be gained by combining simple tests of motor impairment with neuroimaging, genotyping, and neurophysiological assessment of neural plasticity. The development of algorithms to guide the sequential combinations of these assessments could also further increase accuracy, in addition to improving rehabilitation planning and outcomes. Copyright © 2010 Elsevier Ltd. All rights reserved.

Recent research on aetiology, development and phenomenology of self-injurious behaviour in people with intellectual disabilities: a systematic review and implications for treatment.

PubMed

Furniss, F; Biswas, A B

2012-05-01

Behavioural interventions conceptualise self-injurious behaviour (SIB) as developing from early repetitive behaviours through acquisition of homeostatic functions in regulating stimulation and subsequent shaping into SIB through socially mediated or automatic operant reinforcement. Despite high success rates, such interventions rarely completely eliminate SIB, and overall effectiveness has not increased since the 1960s. Research (excluding studies of single genetic syndromes) on the early development, functional properties and phenomenology of SIB in persons with intellectual disabilities (IDs) published from 1999 to 2010 inclusive is reviewed. Despite evidence to support the operant shaping hypothesis, in some cases tissue-damaging SIB, especially head-banging, emerges at a similar or younger age than stereotyped behaviours or 'proto-SIB', often associated with tantrums following frustrative non-reward and/or abrupt situational transitions. Many young children show undifferentiated patterns of responding in functional analyses of SIB, and SIB is associated with aggression and impulsivity as well as with repetitive behaviour. One dynamic in the development of SIB may be Pavlovian conditioning of aggression, originally elicited by aversive events or frustrative non-reward, to stimuli associated with such situations. Integration into operant technology of interventions based on Pavlovian principles such as graduated exposure (with or without counterconditioning) to aversive stimuli may enhance the effectiveness of behavioural interventions. © 2012 The Authors. Journal of Intellectual Disability Research © 2012 Blackwell Publishing Ltd.

Molecular Cloning and Analysis of L(1)ogre, a Locus of Drosophila Melanogaster with Prominent Effects on the Postembryonic Development of the Central Nervous System

PubMed Central

Watanabe, T.; Kankel, D. R.

1990-01-01

Previous genetic studies have shown that wild-type function of the l(1)ogre (lethal (1) optic ganglion reduced) locus is essential for the generation and/or maintenance of the postembryonic neuroblasts including those from which the optic lobe is descended. In the present study molecular isolation and characterization of the l(1)ogre locus was carried out to study the structure and expression of this gene in order to gain information about the nature of l(1)ogre function and its relevance to the development of the central nervous system. About 70 kilobases (kb) of genomic DNA were isolated that spanned the region where l(1)ogre was known to reside. Southern analysis of a l(1)ogre mutation and subsequent P element-mediated DNA transformation mapped the l(1)ogre(+) function within a genomic fragment of 12.5 kb. Northern analyses showed that a 2.9-kb message transcribed from this 12.5-kb region represented l(1)ogre. A 2.15-kb portion of a corresponding cDNA clone was sequenced. An open reading frame (ORF) of 1,086 base pairs was found, and a protein sequence of 362 amino acids with one highly hydrophobic segment was deduced from conceptual translation of this ORF. PMID:1963867

Bioengineering a Human Plasma-Based Epidermal Substitute With Efficient Grafting Capacity and High Content in Clonogenic Cells

PubMed Central

Alexaline, Maia M.; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T.; Doucet, Christelle; Fortunel, Nicolas O.

2015-01-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. Significance This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. PMID:25848122

Bioengineering a human plasma-based epidermal substitute with efficient grafting capacity and high content in clonogenic cells.

PubMed

Alexaline, Maia M; Trouillas, Marina; Nivet, Muriel; Bourreau, Emilie; Leclerc, Thomas; Duhamel, Patrick; Martin, Michele T; Doucet, Christelle; Fortunel, Nicolas O; Lataillade, Jean-Jacques

2015-06-01

Cultured epithelial autografts (CEAs) produced from a small, healthy skin biopsy represent a lifesaving surgical technique in cases of full-thickness skin burn covering >50% of total body surface area. CEAs also present numerous drawbacks, among them the use of animal proteins and cells, the high fragility of keratinocyte sheets, and the immaturity of the dermal-epidermal junction, leading to heavy cosmetic and functional sequelae. To overcome these weaknesses, we developed a human plasma-based epidermal substitute (hPBES) for epidermal coverage in cases of massive burn, as an alternative to traditional CEA, and set up critical quality controls for preclinical and clinical studies. In this study, phenotypical analyses in conjunction with functional assays (clonal analysis, long-term culture, or in vivo graft) showed that our new substitute fulfills the biological requirements for epidermal regeneration. hPBES keratinocytes showed high potential for cell proliferation and subsequent differentiation similar to healthy skin compared with a well-known reference material, as ascertained by a combination of quality controls. This work highlights the importance of integrating relevant multiparameter quality controls into the bioengineering of new skin substitutes before they reach clinical development. This work involves the development of a new bioengineered epidermal substitute with pertinent functional quality controls. The novelty of this work is based on this quality approach. ©AlphaMed Press.

Evolutionary Descent of Prion Genes from the ZIP Family of Metal Ion Transporters

PubMed Central

Schmitt-Ulms, Gerold; Ehsani, Sepehr; Watts, Joel C.; Westaway, David; Wille, Holger

2009-01-01

In the more than twenty years since its discovery, both the phylogenetic origin and cellular function of the prion protein (PrP) have remained enigmatic. Insights into a possible function of PrP may be obtained through the characterization of its molecular neighborhood in cells. Quantitative interactome data demonstrated the spatial proximity of two metal ion transporters of the ZIP family, ZIP6 and ZIP10, to mammalian prion proteins in vivo. A subsequent bioinformatic analysis revealed the unexpected presence of a PrP-like amino acid sequence within the N-terminal, extracellular domain of a distinct sub-branch of the ZIP protein family that includes ZIP5, ZIP6 and ZIP10. Additional structural threading and orthologous sequence alignment analyses argued that the prion gene family is phylogenetically derived from a ZIP-like ancestral molecule. The level of sequence homology and the presence of prion protein genes in most chordate species place the split from the ZIP-like ancestor gene at the base of the chordate lineage. This relationship explains structural and functional features found within mammalian prion proteins as elements of an ancient involvement in the transmembrane transport of divalent cations. The phylogenetic and spatial connection to ZIP proteins is expected to open new avenues of research to elucidate the biology of the prion protein in health and disease. PMID:19784368

Altered emotion regulation capacity in social phobia as a function of comorbidity.

PubMed

Burklund, Lisa J; Craske, Michelle G; Taylor, Shelley E; Lieberman, Matthew D

2015-02-01

Social phobia (SP) has been associated with amygdala hyperreactivity to fear-relevant stimuli. However, little is known about the neural basis of SP individuals' capacity to downregulate their responses to such stimuli and how such regulation varies as a function of comorbid depression and anxiety. We completed an functional magnetic resonance imaging (fMRI) study wherein SP participants without comorbidity (n = 30), with comorbid depression (n = 18) and with comorbid anxiety (n = 19) and healthy controls (n = 15) were scanned while completing an affect labeling emotion regulation task. Individuals with SP as a whole exhibited a reversal of the pattern observed in healthy controls in that they showed upregulation of amygdala activity during affect labeling. However, subsequent analyses revealed a more complex picture based on comorbidity type. Although none of the SP subgroups showed the normative pattern of amygdala downregulation, it was those with comorbid depression specifically who showed significant upregulation. Effects could not be attributed to differences in task performance, amygdala reactivity or right ventral lateral prefrontal cortex (RVLPFC) engagement, but may stem from dysfunctional communication between amygdala and RVLPFC. Furthermore, the particularly altered emotion regulation seen in those with comorbid depression could not be fully explained by symptom severity or state anxiety. Results reveal altered emotion regulation in SP, especially when comorbid with depression. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Dimensions of maternal parenting and infants’ autonomic functioning interactively predict early internalizing behavior problems

PubMed Central

Propper, Cathi; Gueron-Sela, Noa; Mills-Koonce, W. Roger

2015-01-01

Developmental pathways to childhood internalizing behavior problems are complex, with both environmental and child-level factors contributing to their emergence. The authors use data from a prospective longitudinal study (n = 206) to examine the associations between dimensions of caregiving experiences in the first year of life and anxious/depressed and withdrawn behaviors in early childhood. Additionally, the authors examine the extent to which these associations were moderated by infants’ autonomic functioning in the first year of life indexed using measures of respiratory sinus arrhythmia (RSA) and heart period (HP). Findings suggest that higher levels of maternal sensitivity in infancy are associated with fewer anxious/depressed and withdrawn behaviors at age 3 years. Negative intrusiveness was found to be positively associated with children’s anxious/depressed behaviors but not withdrawn behaviors. Further, moderation analyses suggested that the link between negative intrusive parenting during infancy and subsequent anxious/depressed behaviors is exacerbated for infants with average or low baseline HP and that positive engaging parenting during infancy was negatively related to withdrawn behaviors for infants demonstrating average to high levels baseline HP. Interestingly, RSA was not found to moderate the associations between parenting in infancy and later internalizing behavior problems suggesting that, during infancy, overall autonomic functioning may have greater implications for the development of internalizing behaviors than do parasympathetic influences alone. Implications of these findings and future directions for research are discussed. PMID:26063322

Blood pressure and cognitive function: a prospective analysis among adolescents in Seychelles.

PubMed

Lyngdoh, Tanica; Viswanathan, Bharathi; Kobrosly, Roni; van Wijngaarden, Edwin; Huber, Brittany; Davidson, Philip W; Cory-Slechta, Deborah A; Strain, John J; Strain, Sean; Myers, Gary J; Bovet, Pascal

2013-06-01

An inverse relationship between blood pressure (BP) and cognitive function has been found in adults, but limited data are available in adolescents and young adults. We examined the prospective relation between BP and cognitive function in adolescence. We examined the association between BP measured at the ages of 12-15 years in school surveys and cognitive endpoints measured in the Seychelles Child Development Study at ages 17 (n = 407) and 19 (n = 429) years, respectively. We evaluated multiple domains of cognition based on subtests of the Cambridge Neurological Test Automated Battery (CANTAB), the Woodcock Johnson Test of Scholastic Achievement (WJTA), the Finger Tapping test (FT) and the Kaufman Brief Intelligence Test (K-BIT). We used age, sex and height-specific z-scores of SBP, DBP and mean arterial pressure (MAP). Six out of the 21 cognitive endpoints tested were associated with BP. However, none of these associations were found to hold for both males and females or for different subtests within the same neurodevelopmental domain or for both SBP and DBP. Most of these associations disappeared when analyses were adjusted for selected potential confounding factors such as socio-economic status, birth weight, gestational age, BMI, alcohol consumption, blood glucose, and total n-3 and n-6 polyunsaturated fats. Our findings do not support a consistent association between BP and subsequent performance on tests assessing various cognitive domains in adolescents.

Thy1.2 YFP-16 Transgenic Mouse Labels a Subset of Large-Diameter Sensory Neurons that Lack TRPV1 Expression

PubMed Central

Taylor-Clark, Thomas E.; Wu, Kevin Y.; Thompson, Julie-Ann; Yang, Kiseok; Bahia, Parmvir K.; Ajmo, Joanne M.

2015-01-01

The Thy1.2 YFP-16 mouse expresses yellow fluorescent protein (YFP) in specific subsets of peripheral and central neurons. The original characterization of this model suggested that YFP was expressed in all sensory neurons, and this model has been subsequently used to study sensory nerve structure and function. Here, we have characterized the expression of YFP in the sensory ganglia (DRG, trigeminal and vagal) of the Thy1.2 YFP-16 mouse, using biochemical, functional and anatomical analyses. Despite previous reports, we found that YFP was only expressed in approximately half of DRG and trigeminal neurons and less than 10% of vagal neurons. YFP-expression was only found in medium and large-diameter neurons that expressed neurofilament but not TRPV1. YFP-expressing neurons failed to respond to selective agonists for TRPV1, P2X2/3 and TRPM8 channels in Ca2+ imaging assays. Confocal analysis of glabrous skin, hairy skin of the back and ear and skeletal muscle indicated that YFP was expressed in some peripheral terminals with structures consistent with their presumed non-nociceptive nature. In summary, the Thy1.2 YFP-16 mouse expresses robust YFP expression in only a subset of sensory neurons. But this mouse model is not suitable for the study of nociceptive nerves or the function of such nerves in pain and neuropathies. PMID:25746468

Functional Profiling Identifies Genes Involved in Organ-Specific Branches of the PIF3 Regulatory Network in Arabidopsis[C][W

PubMed Central

Sentandreu, Maria; Martín, Guiomar; González-Schain, Nahuel; Leivar, Pablo; Soy, Judit; Tepperman, James M.; Quail, Peter H.; Monte, Elena

2011-01-01

The phytochrome (phy)-interacting basic helix-loop-helix transcription factors (PIFs) constitutively sustain the etiolated state of dark-germinated seedlings by actively repressing deetiolation in darkness. This action is rapidly reversed upon light exposure by phy-induced proteolytic degradation of the PIFs. Here, we combined a microarray-based approach with a functional profiling strategy and identified four PIF3-regulated genes misexpressed in the dark (MIDAs) that are novel regulators of seedling deetiolation. We provide evidence that each one of these four MIDA genes regulates a specific facet of etiolation (hook maintenance, cotyledon appression, or hypocotyl elongation), indicating that there is branching in the signaling that PIF3 relays. Furthermore, combining inferred MIDA gene function from mutant analyses with their expression profiles in response to light-induced degradation of PIF3 provides evidence consistent with a model where the action of the PIF3/MIDA regulatory network enables an initial fast response to the light and subsequently prevents an overresponse to the initial light trigger, thus optimizing the seedling deetiolation process. Collectively, the data suggest that at least part of the phy/PIF system acts through these four MIDAs to initiate and optimize seedling deetiolation, and that this mechanism might allow the implementation of spatial (i.e., organ-specific) and temporal responses during the photomorphogenic program. PMID:22108407

Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system.

PubMed

de Boysson, Hubert; Parienti, Jean-Jacques; Arquizan, Caroline; Boulouis, Grégoire; Gaillard, Nicolas; Régent, Alexis; Néel, Antoine; Detante, Olivier; Touzé, Emanuel; Aouba, Achille; Bienvenu, Boris; Guillevin, Loïc; Naggara, Olivier; Zuber, Mathieu; Pagnoux, Christian

2017-10-01

We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS). We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months' follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up. Ninety-seven patients [46 (47%) female, median age: 46 (18-78) years at diagnosis] were followed up for a median of 55 (5-198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3-18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001]. The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes.

PubMed

Rojas, Daniel; Rager, Julia E; Smeester, Lisa; Bailey, Kathryn A; Drobná, Zuzana; Rubio-Andrade, Marisela; Stýblo, Miroslav; García-Vargas, Gonzalo; Fry, Rebecca C

2015-01-01

Prenatal exposure to inorganic arsenic (iAs) is detrimental to the health of newborns and increases the risk of disease development later in life. Here we examined a subset of newborn cord blood leukocyte samples collected from subjects enrolled in the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, who were exposed to a range of drinking water arsenic concentrations (0.456-236 µg/l). Changes in iAs-associated DNA 5-methylcytosine methylation were assessed across 424,935 CpG sites representing 18,761 genes and compared with corresponding mRNA expression levels and birth outcomes. In the context of arsenic exposure, a total of 2919 genes were identified with iAs-associated differences in DNA methylation. Site-specific analyses identified DNA methylation changes that were most predictive of gene expression levels where CpG methylation within CpG islands positioned within the first exon, the 5' untranslated region and 200 bp upstream of the transcription start site yielded the most significant association with gene expression levels. A set of 16 genes was identified with correlated iAs-associated changes in DNA methylation and mRNA expression and all were highly enriched for binding sites of the early growth response (EGR) and CCCTC-binding factor (CTCF) transcription factors. Furthermore, DNA methylation levels of 7 of these genes were associated with differences in birth outcomes including gestational age and head circumference.These data highlight the complex interplay between DNA methylation, functional changes in gene expression and health outcomes and underscore the need for functional analyses coupled to epigenetic assessments. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated recombination system

PubMed Central

Szczesny, Roman J.; Kowalska, Katarzyna; Klosowska-Kosicka, Kamila; Chlebowski, Aleksander; Owczarek, Ewelina P.; Warkocki, Zbigniew; Kulinski, Tomasz M.; Adamska, Dorota; Affek, Kamila; Jedroszkowiak, Agata; Kotrys, Anna V.; Tomecki, Rafal; Krawczyk, Pawel S.; Borowski, Lukasz S.; Dziembowski, Andrzej

2018-01-01

Deciphering a function of a given protein requires investigating various biological aspects. Usually, the protein of interest is expressed with a fusion tag that aids or allows subsequent analyses. Additionally, downregulation or inactivation of the studied gene enables functional studies. Development of the CRISPR/Cas9 methodology opened many possibilities but in many cases it is restricted to non-essential genes. Recombinase-dependent gene integration methods, like the Flp-In system, are very good alternatives. The system is widely used in different research areas, which calls for the existence of compatible vectors and efficient protocols that ensure straightforward DNA cloning and generation of stable cell lines. We have created and validated a robust series of 52 vectors for streamlined generation of stable mammalian cell lines using the FLP recombinase-based methodology. Using the sequence-independent DNA cloning method all constructs for a given coding-sequence can be made with just three universal PCR primers. Our collection allows tetracycline-inducible expression of proteins with various tags suitable for protein localization, FRET, bimolecular fluorescence complementation (BiFC), protein dynamics studies (FRAP), co-immunoprecipitation, the RNA tethering assay and cell sorting. Some of the vectors contain a bidirectional promoter for concomitant expression of miRNA and mRNA, so that a gene can be silenced and its product replaced by a mutated miRNA-insensitive version. Our toolkit and protocols have allowed us to create more than 500 constructs with ease. We demonstrate the efficacy of our vectors by creating stable cell lines with various tagged proteins (numatrin, fibrillarin, coilin, centrin, THOC5, PCNA). We have analysed transgene expression over time to provide a guideline for future experiments and compared the effectiveness of commonly used inducers for tetracycline-responsive promoters. As proof of concept we examined the role of the exoribonuclease XRN2 in transcription termination by RNAseq. PMID:29590189

New perspective on functional capabilities of microbiome associated with spacecraft assembly facilities

NASA Astrophysics Data System (ADS)

Vaishampayan, Parag

2016-07-01

In compliance with Planetary Protection policy, NASA monitors the total microbial burden of spacecraft and associated environments as a means for minimizing forward contamination. Despite numerous characterizations of microbial populations in spacecraft assembly cleanrooms, understanding the metabolic traits responsible for their persistence and survival remains a significant challenge. The principal objective of this study is to establish functional traits by exploring the entire gene content (metagenome) of the cleanroom microbial community. DNA-based techniques are incapable of distinguishing viable microorganisms from dead microbial cells in samples. Consequently, metagenomic analyses based on total environmental DNA extracts do not render a meaningful understanding of the metabolic and/or functional characteristics of living microorganisms in cleanrooms. A molecular viability marker was applied to samples collected from a cleanroom facility, and subsequent metagenomic sequencing experiments showed considerable differences between the resulting viable-only and total microbiomes. Nevertheless, analyses of sequence abundance suggested that the viable microbiome was influenced by both the human microbiome and the ambient ecosystem external to the facility, which resulted in a complex community profile. Also detected were the first viral signatures ever retrieved from a cleanroom facility: the genomes of human cyclovirus 7078A and Propionibacterium phage P14.4. We also wanted to evaluate if the strict cleaning and decontamination procedures selectively favor survival and growth of hardy microrganisms, such as pathogens. Three geographically distinct cleanrooms were sampled during the assembly of three NASA spacecraft: Dawn, Phoenix, and Mars Science Laboratory. Potential pathogens and their corresponding virulence factors were present in all the samples. Decreased microbial and pathogenic diversity during spacecraft assembly, compared to before and after, indicates that decontamination and preventative measures were effective and well implemented. The findings presented here, as well as the innovative methods that enabled their discovery, promise to have profound implications for the design and interpretation of ongoing and future studies in cleanrooms, indoor environments, and potential future human missions to Mars.

TP89 - SIRZ Decomposition Spectral Estimation

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

Seetho, Isacc M.; Azevedo, Steve; Smith, Jerel

2016-12-08

The primary objective of this test plan is to provide X-ray CT measurements of known materials for the purposes of generating and testing MicroCT and EDS spectral estimates. These estimates are to be used in subsequent Ze/RhoE decomposition analyses of acquired data.

Systematic review of kidney transplantation functional predictors.

PubMed

Miret Alomar, E; Trilla Herrera, E; Lorente Garcia, D; Regis Placido, L; López Del Campo, R; Cuadras Solé, M; Pont Castellana, T; Moreso Mateos, F; Serón Micas, D; Morote Robles, J

2018-05-01

Kidney transplantation from donors with expanded criteria has increased the pool of kidneys at the cost of a higher risk of short and long-term graft dysfunction. The main issue lies in determining which kidneys will offer acceptable function and survival compared with the risk represented by surgery and subsequent immunosuppression. The objective of our article is to review the current evidence on the tools for predicting the functionality of kidney transplantation from cadaveric donors with expanded criteria and determining the validity for their use in standard practice. We conducted a systematic literature review according to the PRISM criteria, through Medline (http://www.ncbi.nlm.nih.gov) and using the keywords (in isolation or in conjunction) "cadaveric renal transplantation; kidney graft function appraisal, graft function predictors". We selected prospective and retrospective series and review articles. A total of 375 articles were analysed, 39 of which were ultimately selected for review. The predictors of functionality include the following: The donor risk indices; the calculation of the renal functional weight or the assessment of the nephronic mass; the measurement of vascular resistances during perfusion in hypothermia; the measurement of the donor's biomarkers in urine and in the perfusion liquid; the measurement of functional and reperfusion parameters in normothermia; and the measurement of morphological parameters (microscopic and macroscopic) of the target organ. In this article, we present an explanatory summary of each of these parameters, as well as their most recent evidence on this issue. None of the reviewed parameters in isolation could reliably predict renal function and graft survival. There is a significant void in terms of the macroscopic assessment of kidney transplantation. We need to continue developing predictors of renal functionality to accurately define the distribution of each currently available donor kidney. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Representation of Letter Position in Spelling: Evidence from Acquired Dysgraphia

PubMed Central

Fischer-Baum, Simon; McCloskey, Michael; Rapp, Brenda

2010-01-01

The graphemic representations that underlie spelling performance must encode not only the identities of the letters in a word, but also the positions of the letters. This study investigates how letter position information is represented. We present evidence from two dysgraphic individuals, CM and LSS, who perseverate letters when spelling: that is, letters from previous spelling responses intrude into subsequent responses. The perseverated letters appear more often than expected by chance in the same position in the previous and subsequent responses. We used these errors to address the question of how letter position is represented in spelling. In a series of analyses we determined how often the perseveration errors produced maintain position as defined by a number of alternative theories of letter position encoding proposed in the literature. The analyses provide strong evidence that the grapheme representations used in spelling encode letter position such that position is represented in a graded manner based on distance from both edges of the word. PMID:20378104

The Impact of Asking Intention or Self-Prediction Questions on Subsequent Behavior

PubMed Central

Wood, Chantelle; Conner, Mark; Miles, Eleanor; Sandberg, Tracy; Taylor, Natalie; Godin, Gaston; Sheeran, Paschal

2015-01-01

The current meta-analysis estimated the magnitude of the impact of asking intention and self-prediction questions on rates of subsequent behavior, and examined mediators and moderators of this question–behavior effect (QBE). Random-effects meta-analysis on 116 published tests of the effect indicated that intention/prediction questions have a small positive effect on behavior (d+ = 0.24). Little support was observed for attitude accessibility, cognitive dissonance, behavioral simulation, or processing fluency explanations of the QBE. Multivariate analyses indicated significant effects of social desirability of behavior/behavior domain (larger effects for more desirable and less risky behaviors), difficulty of behavior (larger effects for easy-to-perform behaviors), and sample type (larger effects among student samples). Although this review controls for co-occurrence of moderators in multivariate analyses, future primary research should systematically vary moderators in fully factorial designs. Further primary research is also needed to unravel the mechanisms underlying different variants of the QBE. PMID:26162771

Analysing the connectivity and communication of suicidal users on twitter

PubMed Central

Colombo, Gualtiero B.; Burnap, Pete; Hodorog, Andrei; Scourfield, Jonathan

2016-01-01

In this paper we aim to understand the connectivity and communication characteristics of Twitter users who post content subsequently classified by human annotators as containing possible suicidal intent or thinking, commonly referred to as suicidal ideation. We achieve this understanding by analysing the characteristics of their social networks. Starting from a set of human annotated Tweets we retrieved the authors’ followers and friends lists, and identified users who retweeted the suicidal content. We subsequently built the social network graphs. Our results show a high degree of reciprocal connectivity between the authors of suicidal content when compared to other studies of Twitter users, suggesting a tightly-coupled virtual community. In addition, an analysis of the retweet graph has identified bridge nodes and hub nodes connecting users posting suicidal ideation with users who were not, thus suggesting a potential for information cascade and risk of a possible contagion effect. This is particularly emphasised by considering the combined graph merging friendship and retweeting links. PMID:26973360

Physical activity trajectories during midlife and subsequent risk of physical functioning decline in late mid-life: The Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Gabriel, Kelley Pettee; Sternfeld, Barbara; Colvin, Alicia; Stewart, Andrea; Strotmeyer, Elsa S.; Cauley, Jane A.; Dugan, Sheila; Karvonen-Gutierrez, Carrie

2018-01-01

The purpose of this study was to examine the importance of midlife physical activity on physical functioning in later life. Data are from 1771 Study of Women’s Health Across the Nation (SWAN) participants, aged 42–52 (46.4 ± 2.7) years at baseline (1996–97). Latent class growth analysis was used to identify physical activity trajectory groups using reported sports and exercise index data collected at seven time-points from baseline to Visit 13 (2011–13); objective measures of physical functioning performance were collected at Visit 13. The sports and exercise index (henceforth: physical activity) is a measure of moderate to vigorous intensity physical activity during discretionary periods of the day. Multivariable linear regression analyses were used to model each continuous physical performance measure as a function of the physical activity trajectory class. Across midlife, five physical activity trajectory classes emerged, including: lowest (26.2% of participants), increasing (13.4%), decreasing (22.4%), middle (23.9%), and highest (14.1%) physical activity. After full adjustment, women included in the middle and highest physical activity groups demonstrated ≥5% better physical functioning performance than those who maintained low physical activity levels (all comparisons; p < 0.05). Statistically significant differences were also noted when physical activity trajectory groups were compared to the increasing physical activity group. Results from the current study support health promotion efforts targeting increased (or maintenance of) habitual physical activity in women during midlife to reduce future risk of functional limitations and disability. These findings have important public health and clinical relevance as future generations continue to transition into older adulthood. PMID:28987336

Acute toxicity of functionalized single wall carbon nanotubes: A biochemical, histopathologic and proteomics approach.

PubMed

Ahmadi, Homa; Ramezani, Mohammad; Yazdian-Robati, Rezvan; Behnam, Behzad; Razavi Azarkhiavi, Kamal; Hashem Nia, Azadeh; Mokhtarzadeh, Ahad; Matbou Riahi, Maryam; Razavi, Bibi Marjan; Abnous, Khalil

2017-09-25

Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice). One or 7 days after intravenous injection, the mice were killed and serum and livers were collected. The oxidative stress markers, biochemical and histopathological changes were studied. Subsequently, proteomics approach was used to investigate the alterations of protein expression profiles in the liver. Results showed that there were not any significant differences in malondealdehyde (MDA), glutathione (GSH) levels and biochemical enzymes (ALT and AST) between groups, while the histopathological observations of livers showed some injuries. The results of proteomics analysis revealed indolethylamine N-Methyltransferase (INMT), glycine N-Methyltransferase (GNMT), selenium binding protein (Selenbp), thioredoxin peroxidase (TPx), TNF receptor associated protein 1(Trap1), peroxiredoxin-6 (Prdx6), electron transport flavoprotein (Etf-α), regucalcin (Rgn) and ATP5b proteins were differentially expressed in functionalized SWCNTs groups. Western blot analyses confirmed that the changes in Prdx6 were consistent with 2-DE gel analysis. In summary, acute toxicological study on two functionalized SWCNTs did not show any significant toxicity at selected doses. Proteomics analysis also showed that following exposure to functionalized SWCNTs, the expression of some proteins with antioxidant activity and detoxifying properties were increased in liver tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Impact of robotic surgery on sexual and urinary functions after fully robotic nerve-sparing total mesorectal excision for rectal cancer.

PubMed

Luca, Fabrizio; Valvo, Manuela; Ghezzi, Tiago Leal; Zuccaro, Massimiliano; Cenciarelli, Sabina; Trovato, Cristina; Sonzogni, Angelica; Biffi, Roberto

2013-04-01

Urinary and sexual dysfunctions are recognized complications of rectal cancer surgery. Their incidence after robotic surgery is as yet unknown. The aim of this study was to prospectively evaluate the impact of robotic surgery for rectal cancer on sexual and urinary functions in male and female patients. From April 2008 to December 2010, 74 patients undergoing fully robotic resection for rectal cancer were prospectively included in the study. Urinary and sexual dysfunctions affecting quality of life were assessed with specific self-administered questionnaires in all patients undergoing robotic total mesorectal excision (RTME). Results were calculated with validated scoring systems and statistically analyzed. The analyses of the questionnaires completed by the 74 patients who underwent RTME showed that sexual function and general sexual satisfaction decreased significantly 1 month after intervention: 19.1 ± 8.7 versus 11.9 ± 10.2 (P < 0.05) for erectile function and 6.9 ± 2.4 versus 5.3 ± 2.5 (P < 0.05) for general satisfaction in men; 2.6 ± 3.3 versus 0.8 ± 1.4 (P < 0.05) and 2.4 ± 2.5 versus 0.7 ± 1.6 (P < 0.05) for arousal and general satisfaction, respectively, in women. Subsequently, both parameters increased progressively, and 1 year after surgery, the values were comparable to those measured before surgery. Concerning urinary function, the grade of incontinence measured 1 year after the intervention was unchanged for both sexes. RTME allows for preservation of urinary and sexual functions. This is probably due to the superior movements of the wristed instruments that facilitate fine dissection, coupled with a stable and magnified view that helps in recognizing the inferior hypogastric plexus.

Network Analysis of Sequence-Function Relationships and Exploration of Sequence Space of TEM β-Lactamases.

PubMed

Zeil, Catharina; Widmann, Michael; Fademrecht, Silvia; Vogel, Constantin; Pleiss, Jürgen

2016-05-01

The Lactamase Engineering Database (www.LacED.uni-stuttgart.de) was developed to facilitate the classification and analysis of TEM β-lactamases. The current version contains 474 TEM variants. Two hundred fifty-nine variants form a large scale-free network of highly connected point mutants. The network was divided into three subnetworks which were enriched by single phenotypes: one network with predominantly 2be and two networks with 2br phenotypes. Fifteen positions were found to be highly variable, contributing to the majority of the observed variants. Since it is expected that a considerable fraction of the theoretical sequence space is functional, the currently sequenced 474 variants represent only the tip of the iceberg of functional TEM β-lactamase variants which form a huge natural reservoir of highly interconnected variants. Almost 50% of the variants are part of a quartet. Thus, two single mutations that result in functional enzymes can be combined into a functional protein. Most of these quartets consist of the same phenotype, or the mutations are additive with respect to the phenotype. By predicting quartets from triplets, 3,916 unknown variants were constructed. Eighty-seven variants complement multiple quartets and therefore have a high probability of being functional. The construction of a TEM β-lactamase network and subsequent analyses by clustering and quartet prediction are valuable tools to gain new insights into the viable sequence space of TEM β-lactamases and to predict their phenotype. The highly connected sequence space of TEM β-lactamases is ideally suited to network analysis and demonstrates the strengths of network analysis over tree reconstruction methods. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Controlled growth of silica-titania hybrid functional nanoparticles through a multistep microfluidic approach.

PubMed

Shiba, K; Sugiyama, T; Takei, T; Yoshikawa, G

2015-11-11

Silica/titania-based functional nanoparticles were prepared through controlled nucleation of titania and subsequent encapsulation by silica through a multistep microfluidic approach, which was successfully applied to obtaining aminopropyl-functionalized silica/titania nanoparticles for a highly sensitive humidity sensor.

Prospective Cohort Study of Work Functioning Impairment and Subsequent Absenteeism Among Japanese Workers.

PubMed

Fujino, Yoshihisa; Shazuki, Shuichiro; Izumi, Hiroyuki; Uehara, Masamichi; Muramatsu, Keiji; Kubo, Tatsuhiko; Oyama, Ichiro; Matsuda, Shinya

2016-07-01

This study examined the association of work functioning impairment as measured by work functioning impairment scale (WFun) and subsequent sick leave. A prospective cohort study was conducted at a manufacturer in Japan, and 1263 employees participated. Information on sick leave was gathered during an 18-month follow-up period. The hazard ratios (HRs) of long-term sick leave were substantially increased for those with a WFun score greater than 25 (HR = 3.99, P = 0.003). The incidence rate ratios (IRRs) of days of short-term absence gradually increased as scores of WFun increased (IRR = 1.18, P < 0.001 in the subjects with WFun of over 25 comparing with those with WFun of 14 or less). Assessing work functioning impairment is a useful way of classifying risk for future sick leave among employees.

Two general models that generate long range correlation

NASA Astrophysics Data System (ADS)

Gan, Xiaocong; Han, Zhangang

2012-06-01

In this paper we study two models that generate sequences with LRC (long range correlation). For the IFT (inverse Fourier transform) model, our conclusion is the low frequency part leads to LRC, while the high frequency part tends to eliminate it. Therefore, a typical method to generate a sequence with LRC is multiplying the spectrum of a white noise sequence by a decaying function. A special case is analyzed: the linear combination of a smooth curve and a white noise sequence, in which the DFA plot consists of two line segments. For the patch model, our conclusion is long subsequences leads to LRC, while short subsequences tend to eliminate it. Therefore, we can generate a sequence with LRC by using a fat-tailed PDF (probability distribution function) of the length of the subsequences. A special case is also analyzed: if a patch model with long subsequences is mixed with a white noise sequence, the DFA plot will consist of two line segments. We have checked known models and actual data, and found they are all consistent with this study.

Corra: Computational framework and tools for LC-MS discovery and targeted mass spectrometry-based proteomics

PubMed Central

Brusniak, Mi-Youn; Bodenmiller, Bernd; Campbell, David; Cooke, Kelly; Eddes, James; Garbutt, Andrew; Lau, Hollis; Letarte, Simon; Mueller, Lukas N; Sharma, Vagisha; Vitek, Olga; Zhang, Ning; Aebersold, Ruedi; Watts, Julian D

2008-01-01

Background Quantitative proteomics holds great promise for identifying proteins that are differentially abundant between populations representing different physiological or disease states. A range of computational tools is now available for both isotopically labeled and label-free liquid chromatography mass spectrometry (LC-MS) based quantitative proteomics. However, they are generally not comparable to each other in terms of functionality, user interfaces, information input/output, and do not readily facilitate appropriate statistical data analysis. These limitations, along with the array of choices, present a daunting prospect for biologists, and other researchers not trained in bioinformatics, who wish to use LC-MS-based quantitative proteomics. Results We have developed Corra, a computational framework and tools for discovery-based LC-MS proteomics. Corra extends and adapts existing algorithms used for LC-MS-based proteomics, and statistical algorithms, originally developed for microarray data analyses, appropriate for LC-MS data analysis. Corra also adapts software engineering technologies (e.g. Google Web Toolkit, distributed processing) so that computationally intense data processing and statistical analyses can run on a remote server, while the user controls and manages the process from their own computer via a simple web interface. Corra also allows the user to output significantly differentially abundant LC-MS-detected peptide features in a form compatible with subsequent sequence identification via tandem mass spectrometry (MS/MS). We present two case studies to illustrate the application of Corra to commonly performed LC-MS-based biological workflows: a pilot biomarker discovery study of glycoproteins isolated from human plasma samples relevant to type 2 diabetes, and a study in yeast to identify in vivo targets of the protein kinase Ark1 via phosphopeptide profiling. Conclusion The Corra computational framework leverages computational innovation to enable biologists or other researchers to process, analyze and visualize LC-MS data with what would otherwise be a complex and not user-friendly suite of tools. Corra enables appropriate statistical analyses, with controlled false-discovery rates, ultimately to inform subsequent targeted identification of differentially abundant peptides by MS/MS. For the user not trained in bioinformatics, Corra represents a complete, customizable, free and open source computational platform enabling LC-MS-based proteomic workflows, and as such, addresses an unmet need in the LC-MS proteomics field. PMID:19087345

Patent information retrieval: approaching a method and analysing nanotechnology patent collaborations.

PubMed

Ozcan, Sercan; Islam, Nazrul

2017-01-01

Many challenges still remain in the processing of explicit technological knowledge documents such as patents. Given the limitations and drawbacks of the existing approaches, this research sets out to develop an improved method for searching patent databases and extracting patent information to increase the efficiency and reliability of nanotechnology patent information retrieval process and to empirically analyse patent collaboration. A tech-mining method was applied and the subsequent analysis was performed using Thomson data analyser software. The findings show that nations such as Korea and Japan are highly collaborative in sharing technological knowledge across academic and corporate organisations within their national boundaries, and China presents, in some cases, a great illustration of effective patent collaboration and co-inventorship. This study also analyses key patent strengths by country, organisation and technology.

The effects of valence and arousal on the neural activity leading to subsequent memory.

PubMed

Mickley Steinmetz, Katherine R; Kensinger, Elizabeth A

2009-11-01

This study examined how valence and arousal affect the processes linked to subsequent memory for emotional information. While undergoing an fMRI scan, participants viewed neutral pictures and emotional pictures varying by valence and arousal. After the scan, participants performed a recognition test. Subsequent memory for negative or high arousal information was associated with occipital and temporal activity, whereas memory for positive or low arousal information was associated with frontal activity. Regression analyses confirmed that for negative or high arousal items, temporal lobe activity was the strongest predictor of later memory whereas for positive or low arousal items, frontal activity corresponded most strongly with later memory. These results suggest that the types of encoding processes relating to memory (e.g., sensory vs. elaborative processing) can differ based on the affective qualities of emotional information.

The effects of valence and arousal on the neural activity leading to subsequent memory

PubMed Central

Mickley Steinmetz, Katherine R.; Kensinger, Elizabeth A.

2010-01-01

This study examined how valence and arousal affect the processes linked to subsequent memory for emotional information. While undergoing an fMRI scan, participants viewed neutral pictures and emotional pictures varying by valence and arousal. After the scan, participants performed a recognition test. Subsequent memory for negative or high arousal information was associated with occipital and temporal activity, while memory for positive or low arousal information was associated with frontal activity. Regression analyses confirmed that for negative or high arousal items, temporal lobe activity was the strongest predictor of later memory whereas for positive or low arousal items, frontal activity corresponded most strongly with later memory. These results suggest that the types of encoding processes relating to memory (e.g., sensory vs. elaborative processing) can differ based on the affective qualities of emotional information. PMID:19674398

A survey of functional behavior assessment methods used by behavior analysts in practice.

PubMed

Oliver, Anthony C; Pratt, Leigh A; Normand, Matthew P

2015-12-01

To gather information about the functional behavior assessment (FBA) methods behavior analysts use in practice, we sent a web-based survey to 12,431 behavior analysts certified by the Behavior Analyst Certification Board. Ultimately, 724 surveys were returned, with the results suggesting that most respondents regularly use FBA methods, especially descriptive assessments. Moreover, the data suggest that the majority of students are being formally taught about the various FBA methods and that educators are emphasizing the range of FBA methods in their teaching. However, less than half of the respondents reported using functional analyses in practice, although many considered descriptive assessments and functional analyses to be the most useful FBA methods. Most respondents reported using informant and descriptive assessments more frequently than functional analyses, and a majority of respondents indicated that they "never" or "almost never" used functional analyses to identify the function of behavior. © Society for the Experimental Analysis of Behavior.