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1.  Conflict Adaptation in Prefrontal Cortex: Now You See It, Now You Don’t 
Daily life requires people to monitor and resolve conflict arising from distracting information irrelevant to current goals. The highly influential conflict monitoring theory (CMT) holds that the anterior cingulate cortex (ACC) detects conflict and subsequently triggers the dorsolateral prefrontal cortex (DLPFC) to regulate that conflict. Multiple lines of evidence have provided support for CMT. For example, performance is faster on incongruent trials that follow other incongruent trials (iI), and is accompanied by reduced ACC and increased DLPFC activation (the conflict adaptation effect). In this fMRI study, we explored whether ACC-DLPFC conflict signaling can result in behavioral adjustments beyond on-line contexts. Participants completed a modified version of the Stroop conflict adaptation paradigm which tested for conflict adaptation effects on the current (N) trial associated with not only by the immediately preceding (N-1) trial, but also 2-back (N-2) trials. Results demonstrated evidence for direct relationships between ACC activity on N-2 trials and both N trial DLPFC activity and behavioral adjustment when intervening trials were congruent (i.e., icI). In contrast, when N-1 trials were incongruent (i.e., iiI), ACC-DLPFC signaling failed and conflict adaptation was absent. These results provide new evidence demonstrating that the conflict monitor-controller maintains previously experienced conflict in the service of subsequent behavioral adjustment. However, the processing of multiple, temporally proximal conflict signals takes a toll on the working memory system, which appears to require re-setting in order to adapt our behavior to frequently changing environmental demands.
doi:10.1016/j.cortex.2013.08.011
PMCID: PMC3872513  PMID: 24074459
Prefrontal cortex; Cognitive control; Conflict adaptation; fMRI
2.  Altered motility of Caulobacter Crescentus in viscous and viscoelastic media 
BMC Microbiology  2014;14(1):322.
Background
Motility of flagellated bacteria depends crucially on their organelles such as flagella and pili, as well as physical properties of the external medium, such as viscosity and matrix elasticity. We studied the motility of wild-type and two mutant strains of Caulobacter crescentus swarmer cells in two different types of media: a viscous and hyperosmotic glycerol-growth medium mixture and a viscoelastic growth medium, containing polyethylene glycol or polyethylene oxide of different defined sizes.
Results
For all three strains in the medium containing glycerol, we found linear drops in percentage of motile cells and decreases in speed of those that remained motile to be inversely proportional to viscosity. The majority of immobilized cells lost viability, evidenced by their membrane leakage. In the viscoelastic media, we found less loss of motility and attenuated decrease of swimming speed at shear viscosity values comparable to the viscous medium. In both types of media, we found more severe loss in percentage of motile cells of wild-type than the mutants without pili, indicating that the interference of pili with flagellated motility is aggravated by increased viscosity. However, we found no difference in swimming speed among all three strains under all test conditions for the cells that remained motile. Finally, the viscoelastic medium caused no significant change in intervals between flagellar motor switches unless the motor stalled.
Conclusion
Hyperosmotic effect causes loss of motility and cell death. Addition of polymers into the cell medium also causes loss of motility due to increased shear viscosity, but the majority of immobilized bacteria remain viable. Both viscous and viscoelastic media alter the motility of flagellated bacteria without affecting the internal regulation of their motor switching behavior.
Electronic supplementary material
The online version of this article (doi:10.1186/s12866-014-0322-3) contains supplementary material, which is available to authorized users.
doi:10.1186/s12866-014-0322-3
PMCID: PMC4302598  PMID: 25539737
Bacterial motility; Hydrodynamics; Hyperosmolarity; Rheology; Viscous agent; Viscoelasticity
3.  Socioeconomic status is positively correlated with frontal white matter integrity in aging 
Age  2012;35(6):2045-2056.
Socioeconomic status (SES) is an important reserve variable which has been shown to benefit the aging brain’s macrostructure. However, it remains unknown whether SES affects age-related changes in the brain’s white matter (WM) microstructure. Here, we used diffusion tensor imaging to explore the relationship between SES and three components of the diffusion tensor [fractional anisotropy (FA), axial diffusivity, and radial diffusivity (DR)]. Participants were 40 (16 male) cognitively normal young adults (mean age = 33.3 years, SD = 4.27) and 44 (19 male) cognitively normal community dwelling seniors (mean age = 66.2 years, SD = 7.5). Age-related FA declines were observed across a large portion of the WM skeleton. However, seniors with high SES showed lower age-related WM integrity declines in three frontal tracts: the right anterior corona radiata and bilateral portions of WM underlying the superior frontal gyri (SFG–WM). Positive SES–FA correlations were primarily driven by negative DR–SES correlations, suggesting that SES may buffer age-related declines in myelin. The functional significance of high SES in these frontal tracts was demonstrated through positive correlations with working memory performance. Possible mechanisms through which SES may attenuate the effects of age on frontal WM integrity are discussed.
doi:10.1007/s11357-012-9493-8
PMCID: PMC3825008  PMID: 23160736
Socioeconomic status; Diffusion tensor imaging; White matter; Brain imaging; Aging; Reserve
4.  Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging 
Neuropsychologia  2013;51(13):10.1016/j.neuropsychologia.2013.09.037.
Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.
doi:10.1016/j.neuropsychologia.2013.09.037
PMCID: PMC3856701  PMID: 24103400
cognitive reserve; brain reserve; bilingualism; DTI; aging
5.  Continuous Exercise but Not High Intensity Interval Training Improves Fat Distribution in Overweight Adults 
Journal of Obesity  2014;2014:834865.
Objective. The purpose of this study was to assess the effect of high intensity interval training (HIIT) versus continuous aerobic exercise training (CONT) or placebo (PLA) on body composition by randomized controlled design. Methods. Work capacity and body composition (dual-energy X-ray absorptiometry) were measured before and after 12 weeks of intervention in 38 previously inactive overweight adults. Results. There was a significant group × time interaction for change in work capacity (P < 0.001), which increased significantly in CONT (23.8 ± 3.0%) and HIIT (22.3 ± 3.5%) but not PLA (3.1 ± 5.0%). There was a near-significant main effect for percentage trunk fat, with trunk fat reducing in CONT by 3.1 ± 1.6% and in PLA by 1.1 ± 0.4%, but not in HIIT (increase of 0.7 ± 1.0%) (P = 0.07). There was a significant reduction in android fat percentage in CONT (2.7 ± 1.3%) and PLA (1.4 ± 0.8%) but not HIIT (increase of 0.8 ± 0.7%) (P = 0.04). Conclusion. These data suggest that HIIT may be advocated as a time-efficient strategy for eliciting comparable fitness benefits to traditional continuous exercise in inactive, overweight adults. However, in this population HIIT does not confer the same benefit to body fat levels as continuous exercise training.
doi:10.1155/2014/834865
PMCID: PMC3942093  PMID: 24669314
6.  The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy 
PLoS Currents  2013;5:ecurrents.md.8273cf41db10e2d15dd3ab827cb4b027.
Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knocks down zebrafish Dystrophin (dmd-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the dmd-MO dystrophic phenotype closely resembles the zebrafish dmd mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the mdx mouse Duchenne model, can rescue muscle fiber damage in both dmd-MO and dmd mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish dmd model for rapid and cost-effective small molecule screening.
doi:10.1371/currents.md.8273cf41db10e2d15dd3ab827cb4b027
PMCID: PMC3870918  PMID: 24459606
7.  WiggleTools: parallel processing of large collections of genome-wide datasets for visualization and statistical analysis 
Bioinformatics  2013;30(7):1008-1009.
Motivation: Using high-throughput sequencing, researchers are now generating hundreds of whole-genome assays to measure various features such as transcription factor binding, histone marks, DNA methylation or RNA transcription. Displaying so much data generally leads to a confusing accumulation of plots. We describe here a multithreaded library that computes statistics on large numbers of datasets (Wiggle, BigWig, Bed, BigBed and BAM), generating statistical summaries within minutes with limited memory requirements, whether on the whole genome or on selected regions.
Availability and Implementation: The code is freely available under Apache 2.0 license at www.github.com/Ensembl/Wiggletools
Contact: zerbino@ebi.ac.uk or flicek@ebi.ac.uk
doi:10.1093/bioinformatics/btt737
PMCID: PMC3967112  PMID: 24363377
8.  Ensembl 2014 
Nucleic Acids Research  2013;42(Database issue):D749-D755.
Ensembl (http://www.ensembl.org) creates tools and data resources to facilitate genomic analysis in chordate species with an emphasis on human, major vertebrate model organisms and farm animals. Over the past year we have increased the number of species that we support to 77 and expanded our genome browser with a new scrollable overview and improved variation and phenotype views. We also report updates to our core datasets and improvements to our gene homology relationships from the addition of new species. Our REST service has been extended with additional support for comparative genomics and ontology information. Finally, we provide updated information about our methods for data access and resources for user training.
doi:10.1093/nar/gkt1196
PMCID: PMC3964975  PMID: 24316576
9.  Lifelong Bilingualism Maintains Neural Efficiency for Cognitive Control in Aging 
Recent behavioral data have shown that lifelong bilingualism can maintain youthful cognitive control abilities in aging. Here, we provide the first direct evidence of a neural basis for the bilingual cognitive control boost in aging. Two experiments were conducted, using a perceptual task switching paradigm, and including a total of 110 participants. In Experiment 1, older adult bilinguals showed better perceptual switching performance than their monolingual peers. In Experiment 2, younger and older adult monolinguals and bilinguals completed the same perceptual task switching experiment while fMRI was performed. Typical age-related performance reductions and fMRI activation increases were observed. However, like younger adults, bilingual older adults outperformed their monolingual peers while displaying decreased activation in left lateral frontal cortex and cingulate cortex. Critically, this attenuation of age-related over-recruitment associated with bilingualism was directly correlated with better task switching performance. In addition, the lower BOLD response in frontal regions accounted for 82% of the variance in the bilingual task switching reaction time advantage. These results suggest that lifelong bilingualism offsets age-related declines in the neural efficiency for cognitive control processes.
doi:10.1523/JNEUROSCI.3837-12.2013
PMCID: PMC3710134  PMID: 23303919
10.  White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions 
Biochimica et Biophysica Acta  2011;1822(3):416-422.
Neuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect grey matter structures associated with memory function. These tracts include parahippocampal WM, the cinglum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD.
doi:10.1016/j.bbadis.2011.07.009
PMCID: PMC3213315  PMID: 21803153
DTI; diffusion tensor imaging; APOE; presymptomatic; Alzheimer's; Alzheimer's risk
11.  Cardiorespiratory Fitness is Positively Correlated with Cerebral White Matter Integrity in Healthy Seniors 
NeuroImage  2011;59(2):1514-1523.
High cardiorespiratory fitness (CRF) is an important protective factor reducing the risk of cardiac-related disability and mortality. Recent research suggests that high CRF also has protective effects on the brain’s macrostructure and functional response. However, little is known about the potential relationship between CRF and the brain’s white matter (WM) microstructure. This study explored the relationship between a comprehensive measure of CRF (VO2 peak, total time on treadmill, and 1-minute heart rate recovery) and multiple diffusion tensor imaging measures of WM integrity. Participants were 26 healthy community dwelling seniors between the ages of 60 and 69 (mean = 64.79 years, SD = 2.8). Results indicated a positive correlation between comprehensive CRF and fractional anisotropy (FA) in a large portion of the corpus callosum. Both VO2 peak and total time on treadmill contributed significantly to explaining the variance in mean FA in this region. The CRF-FA relationship observed in the corpus callosum was primarily characterized by a negative correlation between CRF and radial diffusivity in the absence of CRF correlations with either axial diffusivity or mean diffusivity. Tractography results demonstrated that portions of the corpus callosum associated with CRF primarily involved those interconnecting frontal regions associated with high-level motor planning. These results suggest that high CRF may attenuate age-related myelin declines in portions of the corpus callosum that interconnect homologous premotor cortex regions involved in motor planning.
doi:10.1016/j.neuroimage.2011.08.032
PMCID: PMC3230672  PMID: 21875674
Fitness; Diffusion Tensor Imaging; White Matter; Brain Imaging; Aging; Exercise
12.  Discovery of diversity in xylan biosynthetic genes by transcriptional profiling of a heteroxylan containing mucilaginous tissue 
The exact biochemical steps of xylan backbone synthesis remain elusive. In Arabidopsis, three non-redundant genes from two glycosyltransferase (GT) families, IRX9 and IRX14 from GT43 and IRX10 from GT47, are candidates for forming the xylan backbone. In other plants, evidence exists that different tissues express these three genes at widely different levels, which suggests that diversity in the makeup of the xylan synthase complex exists. Recently we have profiled the transcripts present in the developing mucilaginous tissue of psyllium (Plantago ovata Forsk). This tissue was found to have high expression levels of an IRX10 homolog, but very low levels of the two GT43 family members. This contrasts with recent wheat endosperm tissue profiling that found a relatively high abundance of the GT43 family members. We have performed an in-depth analysis of all GTs genes expressed in four developmental stages of the psyllium mucilagenous layer and in a single stage of the psyllium stem using RNA-Seq. This analysis revealed several IRX10 homologs, an expansion in GT61 (homologs of At3g18170/At3g18180), and several GTs from other GT families that are highly abundant and specifically expressed in the mucilaginous tissue. Our current hypothesis is that the four IRX10 genes present in the mucilagenous tissues have evolved to function without the GT43 genes. These four genes represent some of the most divergent IRX10 genes identified to date. Conversely, those present in the psyllium stem are very similar to those in other eudicots. This suggests these genes are under selective pressure, likely due to the synthesis of the various xylan structures present in mucilage that has a different biochemical role than that present in secondary walls. The numerous GT61 family members also show a wide sequence diversity and may be responsible for the larger number of side chain structures present in the psyllium mucilage.
doi:10.3389/fpls.2013.00183
PMCID: PMC3675317  PMID: 23761806
xylan; psyllium; secondary cell wall; irx; glycosyltransferase; mucilage
13.  OnWARD: Ontology-driven Web-based Framework for Multi-center Clinical Studies 
Journal of biomedical informatics  2011;44(Suppl 1):S48-S53.
With a large percentage of clinical trials still using paper forms as the primary data collection tool, there is much potential for increasing efficiency through web-based data collection systems, especially for large-scale multi-center trials. This paper presents OnWARD, an ontology-driven, secure, rapidly-deployed, web-based framework supporting data capture for large-scale multi-center clinical research. Our approach is developed using the agile methodology to provide a flexible, user-centered dynamic form generator, which can be quickly deployed and customized for any clinical study without the need of deep technical expertise. Because of the flexible framework, the data management system can be extended to accommodate a large variety of data types, including genetic, genomic and proteomic data. In this paper, we demonstrate the initial deployment of OnWARD for a Phase II multi-center clinical trial after a development period of merely three months. The study utilizes 23 clinical report forms containing more than 1500 data points. Preliminary evaluation results show that OnWARD exceeded expectations of the clinical investigators in efficiency, flexibility and ease in setting up.
doi:10.1016/j.jbi.2011.08.019
PMCID: PMC3251701  PMID: 21924379
ontology; clinical research form; dynamic form; web-based data entry
14.  Ensembl 2013 
Nucleic Acids Research  2012;41(Database issue):D48-D55.
The Ensembl project (http://www.ensembl.org) provides genome information for sequenced chordate genomes with a particular focus on human, mouse, zebrafish and rat. Our resources include evidenced-based gene sets for all supported species; large-scale whole genome multiple species alignments across vertebrates and clade-specific alignments for eutherian mammals, primates, birds and fish; variation data resources for 17 species and regulation annotations based on ENCODE and other data sets. Ensembl data are accessible through the genome browser at http://www.ensembl.org and through other tools and programmatic interfaces.
doi:10.1093/nar/gks1236
PMCID: PMC3531136  PMID: 23203987
15.  Common and Distinct Neural Mechanisms of Attentional Switching and Response Conflict 
Brain research  2012;1469:92-102.
The human capacities for overcoming prepotent actions and flexibly switching between tasks represent cornerstones of cognitive control. Functional neuroimaging has implicated a diverse set of brain regions contributing to each of these cognitive control processes. However, the extent to which attentional switching and response conflict draw on shared or distinct neural mechanisms remains unclear. The current study examined the neural correlates of response conflict and attentional switching using event-related functional magnetic resonance imaging (fMRI) and a fully randomized 2×2 design. We manipulated an arrow-word version of the Stroop task to measure conflict and switching in the context of a single task decision, in response to a common set of stimuli. Under these common conditions, both behavioral and imaging data showed significant main effects of conflict and switching but no interaction. However, conjunction analyses identified frontal regions involved in both switching and response conflict, including the dorsal anterior cingulate cortex (dACC) and left inferior frontal junction. In addition, connectivity analyses demonstrated task-dependent functional connectivity patterns between dACC and inferior temporal cortex for attentional switching and between dACC and posterior parietal cortex for response conflict. These results suggest that the brain makes use of shared frontal regions, but can dynamically modulate the connectivity patterns of some of those regions, to deal with attentional switching and response conflict.
doi:10.1016/j.brainres.2012.06.013
PMCID: PMC3411858  PMID: 22750124
Cognitive control; Attentional switching; Response conflict; Prefrontal cortex; fMRI; functional connectivity
16.  Domain General and Domain Preferential Brain Regions Associated with Different Types of Task Switching: A Meta-Analysis 
Human brain mapping  2011;33(1):130-142.
One of our highest evolved functions as human beings is our capacity to switch between multiple tasks effectively. A body of research has identified a distributed frontoparietal network of brain regions which contribute to task switching. However, relatively less is known about whether some brain regions may contribute to switching in a domain-general manner while others may be more preferential for different kinds of switching. To explore this issue, we conducted three meta-analyses focusing on different types of task switching frequently used in the literature (perceptual, response, and context switching), and created a conjunction map of these distinct switch types. A total of 36 switching studies with 562 activation coordinates were analyzed using the activation likelihood estimation method. Common areas associated with switching across switch type included the inferior frontal junction and posterior parietal cortex. In contrast, domain-preferential activation was observed for perceptual switching in the dorsal portion of the premotor cortex and for context switching in frontopolar cortex. Our results suggest that some regions within the frontoparietal network contribute to domain-general switching processes while others contribute to more domain-preferential processes, according to the type of task switch performed.
doi:10.1002/hbm.21199
PMCID: PMC3421461  PMID: 21391260
Cognitive control; Task switching; Meta-analysis; Switch type; Perceptual switching; Response switching; Context switching
17.  CORRELATES OF ADOLESCENT SLEEP TIME AND VARIABILITY IN SLEEP TIME: THE ROLE OF INDIVIDUAL AND HEALTH RELATED CHARACTERISTICS 
Sleep medicine  2011;12(3):239-245.
Objectives
Adolescents are predisposed to short sleep duration and irregular sleep patterns due to certain host characteristics (e.g., age, pubertal status, gender, ethnicity, socioeconomic class, and neighborhood distress) and health-related variables (e.g., ADHD, asthma, birth weight, and BMI). The aim of the current study was to investigate the relationship between such variables and actigraphic measures of sleep duration and variability.
Method
Cross-sectional study of 247 adolescents (48.5% female, 54.3% ethnic minority, mean age of 13.7 years) involved in a larger community-based cohort study.
Results
Significant univariate predictors of sleep duration included gender, minority ethnicity, neighborhood distress, parent income, and BMI. In multivariate models, gender, minority status, and BMI were significantly associated with sleep duration (all p<.05), with girls, non-minority adolescents, and those of a lower BMI obtaining more sleep. Univariate models demonstrated that age, minority ethnicity, neighborhood distress, parent education, parent income, pubertal status, and BMI were significantly related to variability in total sleep time. In the multivariate model, age, minority status, and BMI were significantly related to variability in total sleep time (all p<.05), with younger adolescents, non-minority adolescents, and those of a lower BMI obtaining more regular sleep.
Conclusions
These data show differences in sleep patterns in population sub-groups of adolescents which may be important in understanding pediatric health risk profiles. Subgroups that may particularly benefit from interventions aimed at improving sleep patterns include boys, overweight, and minority adolescents.
doi:10.1016/j.sleep.2010.07.020
PMCID: PMC3050885  PMID: 21316300
18.  High-Volume Resistance Training Session Acutely Diminishes Respiratory Muscle Strength 
This study investigated the effect of a high-volume compared to a low-volume resistance training session on maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Twenty male subjects with resistance training experience (6.2 ± 3.2 y), in a crossover trial, completed two resistance training protocols (high-volume: 5 sets per exercise; low-volume: 2 sets per exercise) and a control session (no exercise) on 3 separate occasions. MIP and MEP decreased by 13.6% (p < 0.01) and 14.7% (p < 0.01) respectively from pre-session MIP and MEP, following the high-volume session. MIP and MEP were unaffected following the low-volume or the control sessions. MIP returned to pre-session values after 40 minutes, whereas MEP remained significantly reduced after 60 minutes post-session by 9.2% compared to pre-session (p < 0.01). The findings suggest that the high-volume session significantly decreased MIP and MEP post-session, implicating a substantially increased demand on the respiratory muscles and that adequate recovery is mandatory following this mode of training.
Key pointsRespiratory muscular strength performance is acutely diminished following a high-volume whole-body resistance training session.Greater ventilatory requirements and generation of IAP during the high-volume resistance training session may have contributed to the increased demand placed on the respiratory muscles.Protracted return of respiratory muscular strength performance to baseline levels may have implications for individuals prior to engaging in subsequent exercise bouts.
PMCID: PMC3737833  PMID: 24149119
Respiratory pressures; core stability; hyperventilation; intra-abdominal pressure; Valsalva maneuver
19.  Ensembl 2012 
Nucleic Acids Research  2011;40(Database issue):D84-D90.
The Ensembl project (http://www.ensembl.org) provides genome resources for chordate genomes with a particular focus on human genome data as well as data for key model organisms such as mouse, rat and zebrafish. Five additional species were added in the last year including gibbon (Nomascus leucogenys) and Tasmanian devil (Sarcophilus harrisii) bringing the total number of supported species to 61 as of Ensembl release 64 (September 2011). Of these, 55 species appear on the main Ensembl website and six species are provided on the Ensembl preview site (Pre!Ensembl; http://pre.ensembl.org) with preliminary support. The past year has also seen improvements across the project.
doi:10.1093/nar/gkr991
PMCID: PMC3245178  PMID: 22086963
20.  Common and Distinct Mechanisms of Cognitive Flexibility in Prefrontal Cortex 
The human ability to flexibly alternate between tasks represents a central component of cognitive control. Neuroimaging studies have linked task switching with a diverse set of prefrontal cortex (PFC) regions but the contributions of these regions to various forms of cognitive flexibility remains largely unknown. Here, subjects underwent functional brain imaging while they completed a paradigm which selectively induced stimulus, response, or cognitive set switches in the context of a single task decision performed on a common set of stimuli. Behavioral results indicated comparable reaction time costs associated with each switch type. Domain-general task switching activation was observed in the inferior frontal junction and posterior parietal cortex, suggesting core roles for these regions in switching such as updating and representing task sets. In contrast, multiple domain-preferential PFC activations were observed across lateral and medial PFC, with progressively more rostral regions recruited as switches became increasingly abstract. Specifically, highly abstract cognitive set switches recruited anterior-PFC regions, moderately abstract response switches recruited mid-PFC regions, and highly constrained stimulus switches recruited posterior-PFC regions. These results demonstrate a functional organization across lateral and medial PFC according to the level of abstraction associated with acts of cognitive flexibility.
doi:10.1523/JNEUROSCI.5923-10.2011
PMCID: PMC3086290  PMID: 21451015
Cognitive control; Task switching; Prefrontal cortex; Stimulus switching; Response switching; Set switching
21.  Ensembl 2011 
Nucleic Acids Research  2010;39(Database issue):D800-D806.
The Ensembl project (http://www.ensembl.org) seeks to enable genomic science by providing high quality, integrated annotation on chordate and selected eukaryotic genomes within a consistent and accessible infrastructure. All supported species include comprehensive, evidence-based gene annotations and a selected set of genomes includes additional data focused on variation, comparative, evolutionary, functional and regulatory annotation. The most advanced resources are provided for key species including human, mouse, rat and zebrafish reflecting the popularity and importance of these species in biomedical research. As of Ensembl release 59 (August 2010), 56 species are supported of which 5 have been added in the past year. Since our previous report, we have substantially improved the presentation and integration of both data of disease relevance and the regulatory state of different cell types.
doi:10.1093/nar/gkq1064
PMCID: PMC3013672  PMID: 21045057
22.  Relationships Among Sleepiness, Sleep Time, and Psychological Functioning in Adolescents 
Journal of Pediatric Psychology  2009;34(10):1175-1183.
Objective This study examined associations among adolescent sleepiness, sleep duration, variability in sleep duration, and psychological functioning (symptoms of anxiety, depression, externalizing behaviors, and perceived health). Methods This was a cross-sectional analysis of data from a community-based cohort study of sleep and health. Participants were 247 adolescents (48.6% female, 54.3% ethnic minority, mean age of 13.7 years). Sleep duration and variability in sleep duration were measured by actigraphy and sleepiness was measured by adolescent questionnaire. Primary outcomes were measured by parent, teacher, and adolescent questionnaires. Results Sleepiness was associated with higher scores on measures of anxiety (Adjusted partial r2 = .28, p < .001), depression (Adjusted partial r2 = .23, p < .001), and perceived health (indicating more negative outcomes) (Adjusted partial r2 = .19, p < .01). Significant associations between sleep duration or variability in sleep duration with psychological variables were not found. Conclusions Findings highlight the inter-relationships between sleepiness and psychological functioning and the potential importance of addressing sleepiness in health and psychological evaluations of adolescents.
doi:10.1093/jpepsy/jsp039
PMCID: PMC2782255  PMID: 19494088
adolescents; sleep; psychosocial functioning.
23.  Obesity and obesity related co-morbidities in a referral population of children with asthma 
Pediatric pulmonology  2009;44(9):877-884.
Objective
Although there is mounting evidence that childhood obesity is a risk factor for incident asthma, it remains unclear if there is a distinct “asthma-obesity” phenotype. This study characterized body composition, obesity related co-morbidities, and traditional risk factors for asthma in a cohort of children referred for asthma management in a pulmonary clinic. We hypothesized that children with asthma and obesity would have distinct risk factors and co-morbidities, particularly with respect to metabolic and sleep abnormalities.
Participants and Methods
116 asthmatic children ages 4 to 18 years underwent comprehensive measurements of common asthma risk factors as well as measurements of obesity-related morbidities, including lung function tests, atopy, and assessments of sleep (overnight oximetry and actigraphy), physical activity (accelerometry), and metabolism. Characteristics of children who were obese (BMI ≥ 95th percentile) were compared to those who were not obese (BMI < 95th percentile).
Results
Obesity was present in 44% of participants. Obese participants had similar rates of atopy and family history of atopy, lung function, and asthma control at enrollment as their non-obese peers. A significantly higher proportion of obese participants had metabolic syndrome (23% vs 0%) and habitual snoring (60% vs 33%) compared to non-obese participants; insufficient sleep and nocturnal desaturations tended to be more prevalent among obese subjects.
Conclusions
Obesity and obesity related co-morbidities were common in a referral population of children with asthma. The specific influence of metabolic abnormalities on asthma morbidity and management is still uncertain and likely will need to be addressed in prospective studies.
doi:10.1002/ppul.21065
PMCID: PMC2940418  PMID: 19639627
obesity; asthma
24.  Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array 
Pharmaceutical Research  2010;28(1):31-40.
ABSTRACT
Purpose
The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application.
Methods
3M’s hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins. Blood samples were collected after delivery and analyzed via HPLC or ELISA to provide a PK profile for the delivered drug. Site evaluations were conducted post delivery to determine skin tolerability.
Results
Up to 1.5 mL of formulation was infused into swine at a max rate of approximately 0.25 mL/min. A red blotch, the size of the hMTS array, was observed immediately after patch removal, but had faded so as to be almost indistinguishable 10 min post-patch removal. One-mL deliveries of commercial formulations of naloxone hydrochloride and human growth hormone and a formulation of equine anti-tetanus toxin were completed in swine. With few notable differences, the resulting PK profiles were similar to those achieved following subcutaneous injection of these formulations.
Conclusions
3M’s hMTS can provide rapid, intradermal delivery of 300–1,500 µL of liquid formulations of small molecules salts and proteins, compounds not typically compatible with passive transdermal delivery.
doi:10.1007/s11095-010-0177-8
PMCID: PMC3003827  PMID: 20582455
transdermal drug delivery; microneedles; intradermal; hollow microstructures; MTS
25.  Consistent annotation of gene expression arrays 
BMC Genomics  2010;11:294.
Background
Gene expression arrays are valuable and widely used tools for biomedical research. Today's commercial arrays attempt to measure the expression level of all of the genes in the genome. Effectively translating the results from the microarray into a biological interpretation requires an accurate mapping between the probesets on the array and the genes that they are targeting. Although major array manufacturers provide annotations of their gene expression arrays, the methods used by various manufacturers are different and the annotations are difficult to keep up to date in the rapidly changing world of biological sequence databases.
Results
We have created a consistent microarray annotation protocol applicable to all of the major array manufacturers. We constantly keep our annotations updated with the latest Ensembl Gene predictions, and thus cross-referenced with a large number of external biomedical sequence database identifiers. We show that these annotations are accurate and address in detail reasons for the minority of probesets that cannot be annotated. Annotations are publicly accessible through the Ensembl Genome Browser and programmatically through the Ensembl Application Programming Interface. They are also seamlessly integrated into the BioMart data-mining tool and the biomaRt package of BioConductor.
Conclusions
Consistent, accurate and updated gene expression array annotations remain critical for biological research. Our annotations facilitate accurate biological interpretation of gene expression profiles.
doi:10.1186/1471-2164-11-294
PMCID: PMC2894801  PMID: 20459806

Results 1-25 (33)