Functional recovery differences after stroke rehabilitation in patients with uni- or bilateral hemiparesis

PubMed Central

Bindawas, Saad M.; Mawajdeh, Hussam M.; Vennu, Vishal S.; Alhaidary, Hisham M.

2017-01-01

Objective: To examine the functional recovery differences after stroke rehabilitation in patients with uni- or bilateral hemiparesis. Methods: In this retrospective study, we included data from the medical record of all 383 patients with uni- or bilateral hemiparesis after stroke who were admitted to King Fahad Medical City-Rehabilitation Hospital between 2008 and 2014 in Riyadh, Kingdom of Saudi Arabia. According to the site of hemiparesis, we classified patients into 3 groups: right hemiparesis (n=208), left hemiparesis (n=157), and bilateral hemipareses (n=18). The patients (n=49) who did not have either site of hemiparesis were excluded. The Functional Independence Measures (FIM) instrument was used to assess the score at admission and discharge. A post hoc test was conducted to examine the functional recovery differences between groups. Multiple regression analyses were used to confirm the findings. Results: Amongst the three groups, there were significant (p<0.05) differences in the total-FIM score as well as motor- and cognitive-FIM sub-scores between admission and discharge of stroke rehabilitation. The differences were significantly greater in the bilateral hemipareses group than in either unilateral hemiparesis group. Multiple regression analyses also confirmed that the site of hemiparesis significantly (p<0.05) differs in the total-FIM score as well as motor-FIM and cognitive-FIM sub-scores. Conclusion: Our results demonstrate that differences in functional recovery after stroke rehabilitation may be influenced by the site of hemiparesis after stroke. PMID:28678212

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

PubMed

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Skin problems of the stump in lower-limb amputees: 2. Influence on functioning in daily life.

PubMed

Meulenbelt, Henk E J; Geertzen, Jan H B; Jonkman, Marcel F; Dijkstra, Pieter U

2011-03-01

The aim of this study was to analyse the influence of stump skin problems on functioning in daily life in lower-limb amputees. A cross-sectional study was performed by means of a questionnaire containing 9 questions assessing functioning in daily life. Question scores were added to give a total score (range 0 (no influence) to 27 (maximum negative influence)). Two thousand and thirty-nine people were invited to participate, with 805 participants completing a questionnaire. Of these, 507 reported one or more skin problems. Skin problems had a negative influence on ability to perform household tasks, prosthesis use, social functioning, and participation in sports. The mean total score was 5.5 ± 4.1. This correlated significantly with the number of skin complaints (r = 0.483; p = 0.01). In linear regression analyses, gender (β = -0.15) and number of skin problems (β = 0.25) accounted for 23% of the total score. This study confirms the influence of skin problems on functioning in daily life.

Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species closely related to the zebrafish

PubMed Central

Zardoya, Rafael; Abouheif, Ehab; Meyer, Axel

1996-01-01

The study of development has relied primarily on the isolation of mutations in genes with specific functions in development and on the comparison of their expression patterns in normal and mutant phenotypes. Comparative evolutionary analyses can complement these approaches. Phylogenetic analyses of Sonic hedgehog (Shh) and Hoxd-10 genes from 18 cyprinid fish species closely related to the zebrafish provide novel insights into the functional constraints acting on Shh. Our results confirm and extend those gained from expression and crystalline structure analyses of this gene. Unexpectedly, exon 1 of Shh is found to be almost invariant even in third codon positions among these morphologically divergent species suggesting that this exon encodes for a functionally important domain of the hedgehog protein. This is surprising because the main functional domain of Shh had been thought to be that encoded by exon 2. Comparisons of Shh and Hoxd-10 gene sequences and of resulting gene trees document higher evolutionary constraints on the former than on the latter. This might be indicative of more general evolutionary patterns in networks of developmental regulatory genes interacting in a hierarchical fashion. The presence of four members of the hedgehog gene family in cyprinid fishes was documented and their homologies to known hedgehog genes in other vertebrates were established. PMID:8917540

Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species closely related to the zebrafish.

PubMed

Zardoya, R; Abouheif, E; Meyer, A

1996-11-12

The study of development has relied primarily on the isolation of mutations in genes with specific functions in development and on the comparison of their expression patterns in normal and mutant phenotypes. Comparative evolutionary analyses can complement these approaches. Phylogenetic analyses of Sonic hedgehog (Shh) and Hoxd-10 genes from 18 cyprinid fish species closely related to the zebrafish provide novel insights into the functional constraints acting on Shh. Our results confirm and extend those gained from expression and crystalline structure analyses of this gene. Unexpectedly, exon 1 of Shh is found to be almost invariant even in third codon positions among these morphologically divergent species suggesting that this exon encodes for a functionally important domain of the hedgehog protein. This is surprising because the main functional domain of Shh had been thought to be that encoded by exon 2. Comparisons of Shh and Hoxd-10 gene sequences and of resulting gene trees document higher evolutionary constraints on the former than on the latter. This might be indicative of more general evolutionary patterns in networks of developmental regulatory genes interacting in a hierarchical fashion. The presence of four members of the hedgehog gene family in cyprinid fishes was documented and their homologies to known hedgehog genes in other vertebrates were established.

Large-Scale Comparative Phenotypic and Genomic Analyses Reveal Ecological Preferences of Shewanella Species and Identify Metabolic Pathways Conserved at the Genus Level ▿ †

PubMed Central

Rodrigues, Jorge L. M.; Serres, Margrethe H.; Tiedje, James M.

2011-01-01

The use of comparative genomics for the study of different microbiological species has increased substantially as sequence technologies become more affordable. However, efforts to fully link a genotype to its phenotype remain limited to the development of one mutant at a time. In this study, we provided a high-throughput alternative to this limiting step by coupling comparative genomics to the use of phenotype arrays for five sequenced Shewanella strains. Positive phenotypes were obtained for 441 nutrients (C, N, P, and S sources), with N-based compounds being the most utilized for all strains. Many genes and pathways predicted by genome analyses were confirmed with the comparative phenotype assay, and three degradation pathways believed to be missing in Shewanella were confirmed as missing. A number of previously unknown gene products were predicted to be parts of pathways or to have a function, expanding the number of gene targets for future genetic analyses. Ecologically, the comparative high-throughput phenotype analysis provided insights into niche specialization among the five different strains. For example, Shewanella amazonensis strain SB2B, isolated from the Amazon River delta, was capable of utilizing 60 C compounds, whereas Shewanella sp. strain W3-18-1, isolated from deep marine sediment, utilized only 25 of them. In spite of the large number of nutrient sources yielding positive results, our study indicated that except for the N sources, they were not sufficiently informative to predict growth phenotypes from increasing evolutionary distances. Our results indicate the importance of phenotypic evaluation for confirming genome predictions. This strategy will accelerate the functional discovery of genes and provide an ecological framework for microbial genome sequencing projects. PMID:21642407

Design data needs modular high-temperature gas-cooled reactor. Revision 2

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

NONE

1987-03-01

The Design Data Needs (DDNs) provide summary statements for program management, of the designer`s need for experimental data to confirm or validate assumptions made in the design. These assumptions were developed using the Integrated Approach and are tabulated in the Functional Analysis Report. These assumptions were also necessary in the analyses or trade studies (A/TS) to develop selections of hardware design or design requirements. Each DDN includes statements providing traceability to the function and the associated assumption that requires the need.

Synthesis, growth, structural, spectroscopic and optical studies of a new semiorganic nonlinear optical crystal: L-valine hydrochloride.

PubMed

Kirubavathi, K; Selvaraju, K; Valluvan, R; Vijayan, N; Kumararaman, S

2008-04-01

Single crystals of a new semiorganic nonlinear optical (NLO) material, L-valine hydrochloride (LVHCl), having dimensions up to 20 mm x 6 mm x 4 mm have been grown by slow evaporation solution growth technique. Single crystal X-ray diffraction studies confirm that the grown crystal belongs to the monoclinic system. The functional groups presented in the crystal were confirmed by Fourier transform infrared (FTIR) technique. Optical transmission spectrum shows very low absorption in the entire visible region. Differential thermal and thermogravimetric analyses confirmed that the crystal is stable up to 211 degrees C. The powder second harmonic generation (SHG) efficiency of LVHCl is 1.7 times efficient as potassium dihydrogen phosphate (KDP).

Porcine uterus cryopreservation: an analysis of contractile function using different uterotonics.

PubMed

Schölch, Daniel; Schölch, Sebastian; Strahl, Olga; Hoffmann, Inge; Beckmann, Matthias W; Dittrich, Ralf

2012-10-01

Cryopreservation of whole organs has become increasingly successful in recent years, and establishing reliable methods for confirming the success of specific cryopreservation procedures has therefore become extremely important. On the assumption that methods such as histological evaluation do not provide definitive evidence of long-term cryopreservation and that clear signs of conserved function in an organ are good evidence of its viability, contractile function was analysed in porcine uteri (n=60), either after long-term (group A) or short-term (group B) cryopreservation and post-thaw treatment with three different uterotonics. A slow freezing protocol was used to preserve the organs. Fifteen fresh uteri were analysed similarly for contractile function, which was evaluated by measuring intrauterine pressure after administration of oxytocin, prostaglandin E(1) (PGE(1)), and carbachol. After cryopreservation, all but three uteri (95%) showed rhythmic contractions similar to those in fresh uteri except for differences in the heights of contraction peaks, with lower contractions in PGE(1) subgroup B (P<0.05). With the exception of three nonresponsive uteri in group A, there were no differences in contractility between uteri after long-term cryopreservation and fresh uteri. The results of this study thus contribute to the debate on whether slow freezing or vitrification techniques are best for whole-organ cryopreservation. In summary, (1) preservation of muscular function in porcine uteri is feasible with a slow freezing protocol; (2) measurement of contractile function following administration of uterotonics is a useful method of confirming functionality; and (3) long-term cryopreservation does not significantly impair post-thaw contractibility in comparison with fresh uteri. Copyright © 2012 Elsevier Inc. All rights reserved.

A confirmative clinimetric analysis of the 36-item Family Assessment Device.

PubMed

Timmerby, Nina; Cosci, Fiammetta; Watson, Maggie; Csillag, Claudio; Schmitt, Florence; Steck, Barbara; Bech, Per; Thastum, Mikael

2018-02-07

The Family Assessment Device (FAD) is a 60-item questionnaire widely used to evaluate self-reported family functioning. However, the factor structure as well as the number of items has been questioned. A shorter and more user-friendly version of the original FAD-scale, the 36-item FAD, has therefore previously been proposed, based on findings in a nonclinical population of adults. We aimed in this study to evaluate the brief 36-item version of the FAD in a clinical population. Data from a European multinational study, examining factors associated with levels of family functioning in adult cancer patients' families, were used. Both healthy and ill parents completed the 60-item version FAD. The psychometric analyses conducted were Principal Component Analysis and Mokken-analysis. A total of 564 participants were included. Based on the psychometric analysis we confirmed that the 36-item version of the FAD has robust psychometric properties and can be used in clinical populations. The present analysis confirmed that the 36-item version of the FAD (18 items assessing 'well-being' and 18 items assessing 'dysfunctional' family function) is a brief scale where the summed total score is a valid measure of the dimensions of family functioning. This shorter version of the FAD is, in accordance with the concept of 'measurement-based care', an easy to use scale that could be considered when the aim is to evaluate self-reported family functioning.

Hippocampal hypometabolism in older adults with memory complaints and increased amyloid burden.

PubMed

Vannini, Patrizia; Hanseeuw, Bernard; Munro, Catherine E; Amariglio, Rebecca E; Marshall, Gad A; Rentz, Dorene M; Pascual-Leone, Alvaro; Johnson, Keith A; Sperling, Reisa A

2017-05-02

To identify the functional and pathologic correlates underlying subjective memory complaints (SMCs) in cognitively normal older adults. Two hundred fifty-one older adults underwent resting-state fluorodeoxyglucose (FDG)-PET and Pittsburg compound B-PET β-amyloid (Aβ) imaging and filled out a questionnaire regarding SMCs. Participants were classified into 2 groups based on their Aβ burden. Age-adjusted voxel-wise correlations were used to examine SMCs, amyloid status (Aβ + vs Aβ - ), and the interaction between SMCs and Aβ status as predictors of metabolism. Region-of-interest (ROI) analyses were performed to confirm the whole-brain analyses and to test for additional covariates. Greater SMCs correlated with decreased FDG metabolism in the bilateral precuneus, bilateral inferior parietal lobes, right inferior temporal lobe, right medial frontal gyrus, and right orbitofrontal gyrus. A significant interaction effect between SMCs and amyloid burden was found such that Aβ + individuals with increased complaints had decreased FDG metabolism in the bilateral medial temporal lobes. ROI analyses confirmed the voxel-wise analyses result in that decreased precuneus metabolism was associated with greater SMCs regardless of Aβ status, age, or thickness, whereas the relationship between hippocampal metabolism and SMCs was a function of Aβ, even after adjustment for age, hippocampal volume, or depressive symptoms. These data show the relevant role of posterior and anterior midline regions in SMCs in older individuals. Decreased hippocampal metabolism may be a specific marker of subclinical changes in cognition due to amyloid pathology. However, longitudinal studies are needed to determine whether our findings foreshadow clinical decline. © 2017 American Academy of Neurology.

Development of a local size hierarchy causes regular spacing of trees in an even-aged Abies forest: analyses using spatial autocorrelation and the mark correlation function.

PubMed

Suzuki, Satoshi N; Kachi, Naoki; Suzuki, Jun-Ichirou

2008-09-01

During the development of an even-aged plant population, the spatial distribution of individuals often changes from a clumped pattern to a random or regular one. The development of local size hierarchies in an Abies forest was analysed for a period of 47 years following a large disturbance in 1959. In 1980 all trees in an 8 x 8 m plot were mapped and their height growth after the disturbance was estimated. Their mortality and growth were then recorded at 1- to 4-year intervals between 1980 and 2006. Spatial distribution patterns of trees were analysed by the pair correlation function. Spatial correlations between tree heights were analysed with a spatial autocorrelation function and the mark correlation function. The mark correlation function was able to detect a local size hierarchy that could not be detected by the spatial autocorrelation function alone. The small-scale spatial distribution pattern of trees changed from clumped to slightly regular during the 47 years. Mortality occurred in a density-dependent manner, which resulted in regular spacing between trees after 1980. The spatial autocorrelation and mark correlation functions revealed the existence of tree patches consisting of large trees at the initial stage. Development of a local size hierarchy was detected within the first decade after the disturbance, although the spatial autocorrelation was not negative. Local size hierarchies that developed persisted until 2006, and the spatial autocorrelation became negative at later stages (after about 40 years). This is the first study to detect local size hierarchies as a prelude to regular spacing using the mark correlation function. The results confirm that use of the mark correlation function together with the spatial autocorrelation function is an effective tool to analyse the development of a local size hierarchy of trees in a forest.

Association between social contact frequency and negative symptoms, psychosocial functioning and quality of life in patients with schizophrenia.

PubMed

Siegrist, Karin; Millier, Aurelie; Amri, Ikbal; Aballéa, Samuel; Toumi, Mondher

2015-12-30

The lack of social contacts may be an important element in the presumed vicious circle aggravating, or at least stabilising negative symptoms in patients with schizophrenia. A European 2-year cohort study collected negative symptom scores, psychosocial functioning scores, objective social contact frequency scores and quality of life scores every 6 months. Bivariate analyses, correlation analyses, multivariate regressions and random effects regressions were conducted to describe relations between social contact and outcomes of interest and to gain a better understanding of this relation over time. Using data from 1208 patients with schizophrenia, a link between social contact frequency and negative symptom scores, functioning and quality of life at baseline was established. Regression models confirmed the significant association between social contact and negative symptoms as well as psychosocial functioning. This study aimed at demonstrating the importance of social contact for deficient behavioural aspects of schizophrenia. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

The TRANSPARENT TESTA16 Locus Encodes the ARABIDOPSIS BSISTER MADS Domain Protein and Is Required for Proper Development and Pigmentation of the Seed Coat

PubMed Central

Nesi, Nathalie; Debeaujon, Isabelle; Jond, Clarisse; Stewart, Amanda J.; Jenkins, Gareth I.; Caboche, Michel; Lepiniec, Loïc

2002-01-01

Screening for seed pigmentation phenotypes in Arabidopsis led to the isolation of three allelic yellow-seeded mutants, which defined the novel TRANSPARENT TESTA16 (TT16) locus. Cloning of TT16 was performed by T-DNA tagging and confirmed by genetic complementation and sequencing of two mutant alleles. TT16 encodes the ARABIDOPSIS BSISTER (ABS) MADS domain protein. ABS belongs to the recently identified “B-sister” (BS) clade, which contains genes of unknown function that are expressed mainly in female organs. Phylogenetic analyses using a maximum parsimony approach confirmed that TT16/ABS and related proteins form a monophyletic group. TT16/ABS was expressed mainly in the ovule, as are the other members of the BS clade. TT16/ABS is necessary for BANYULS expression and proanthocyanidin accumulation in the endothelium of the seed coat, with the exception of the chalazal-micropylar area. In addition, mutant phenotype and ectopic expression analyses suggested that TT16/ABS also is involved in the specification of endothelial cells. Nevertheless, TT16/ABS apparently is not required for proper ovule function. We report the functional characterization of a member of the BS MADS box gene subfamily, demonstrating its involvement in endothelial cell specification as well as in the increasingly complex genetic control of flavonoid biosynthesis in the Arabidopsis seed coat. PMID:12368498

Differential Adjustment Among Rural Adolescents Exposed to Family Violence

PubMed Central

Sianko, Natallia; Hedge, Jasmine M.; McDonell, James R.

2016-01-01

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents’ reactions to violence. Implications for future research and practical interventions are discussed. PMID:27106255

Stuttering, Induced Fluency, and Natural Fluency: A Hierarchical Series of Activation Likelihood Estimation Meta-Analyses

PubMed Central

Budde, Kristin S.; Barron, Daniel S.; Fox, Peter T.

2015-01-01

Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as “neural signatures of stuttering” (Brown 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: 1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and 2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). PMID:25463820

The relationship between social functioning and subjective memory complaints in older persons: a population-based longitudinal cohort study.

PubMed

Kuiper, Jisca S; Oude Voshaar, Richard C; Zuidema, Sytse U; Stolk, Ronald P; Zuidersma, Marij; Smidt, Nynke

2017-10-01

Poor social functioning is associated with cognitive decline in older adults. It is unclear whether social functioning is also associated with subjective memory complaints (SMC). We investigated the association between social functioning and incident SMC and SMC recovery. A population-based sample of 8762 older adults (aged ≥65 years) with good objective cognitive functioning at baseline (MMSE ≥26) from the LifeLines Cohort Study were followed for 1.5 years. Self-reported SMC were measured at baseline and after 1.5 years follow-up. Aspects of social functioning included marital status, household composition, social network size, social activity, quality of social relationships, social support, affection, behavioral confirmation, and status. Thirteen percent (513/3963) developed SMC during follow-up (incident SMC). Multivariate logistic regression analyses (adjusted for age, gender, education level, physical activity, alcohol use, smoking status, depression, arrhythmia, myocardial infarction, heart failure, stroke) showed that participants with better feelings of affection, behavioral confirmation and stable good social support had a lower risk of incident SMC. Thirty-four percent (1632/4799) reported recovery. Participants with good social functioning at baseline on all determinants reported more SMC recovery. People who remained stable in a relationship, stable in good quality of social relationships or increased in quality of social relationships more often report SMC recovery. Good social functioning is associated with less incident SMC and more SMC recovery over a follow-up period of 1.5 years. Albeit future confirmative studies are needed, we argue for targeting also social functioning when designing multidomain interventions to prevent or slow down cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

NEK1 variants confer susceptibility to amyotrophic lateral sclerosis

PubMed Central

Kenna, Kevin P; van Doormaal, Perry T C; Dekker, Annelot M; Ticozzi, Nicola; Kenna, Brendan J; Diekstra, Frank P; van Rheenen, Wouter; van Eijk, Kristel R; Jones, Ashley R; Keagle, Pamela; Shatunov, Aleksey; Sproviero, William; Smith, Bradley N; van Es, Michael A; Topp, Simon D; Kenna, Aoife; Miller, Jack W; Fallini, Claudia; Tiloca, Cinzia; McLaughlin, Russell L; Vance, Caroline; Troakes, Claire; Colombrita, Claudia; Mora, Gabriele; Calvo, Andrea; Verde, Federico; Al-Sarraj, Safa; King, Andrew; Calini, Daniela; de Belleroche, Jacqueline; Baas, Frank; van der Kooi, Anneke J; de Visser, Marianne; Asbroek, Anneloor L M A ten; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Muñoz-Blanco, José Luis; Strom, Tim M; Meitinger, Thomas; Morrison, Karen E; Lauria, Giuseppe; Williams, Kelly L; Leigh, P Nigel; Nicholson, Garth A; Blair, Ian P; Leblond, Claire S; Dion, Patrick A; Rouleau, Guy A; Pall, Hardev; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Taroni, Franco; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Esteban-Pérez, Jesús; García-Redondo, Alberto; Van Damme, Phillip; Robberecht, Wim; Chio, Adriano; Gellera, Cinzia; Drepper, Carsten; Sendtner, Michael; Ratti, Antonia; Glass, Jonathan D; Mora, Jesús S; Basak, Nazli A; Hardiman, Orla; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Brown, Robert H; Al-Chalabi, Ammar; Silani, Vincenzo; Shaw, Christopher E; van den Berg, Leonard H; Veldink, Jan H; Landers, John E

2017-01-01

To identify genetic factors contributing to amyotrophic lateral sclerosis (ALS), we conducted whole-exome analyses of 1,022 index familial ALS (FALS) cases and 7,315 controls. In a new screening strategy, we performed gene-burden analyses trained with established ALS genes and identified a significant association between loss-of-function (LOF) NEK1 variants and FALS risk. Independently, autozygosity mapping for an isolated community in the Netherlands identified a NEK1 p.Arg261His variant as a candidate risk factor. Replication analyses of sporadic ALS (SALS) cases and independent control cohorts confirmed significant disease association for both p.Arg261His (10,589 samples analyzed) and NEK1 LOF variants (3,362 samples analyzed). In total, we observed NEK1 risk variants in nearly 3% of ALS cases. NEK1 has been linked to several cellular functions, including cilia formation, DNA-damage response, microtubule stability, neuronal morphology and axonal polarity. Our results provide new and important insights into ALS etiopathogenesis and genetic etiology. PMID:27455347

Correlation of tryptophan fluorescence intensity decay parameters with sup 1 H NMR-determined rotamer conformations: (tryptophan sup 2 )oxytocin

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

Ross, J.B.A.; Schwartz, G.P.; Laws, W.R.

1992-02-18

While the fluorescence decay kinetics of tyrosine model compounds can be explained in terms of heterogeneity derived from the three ground-state {chi}{sup 1} rotamers, a similar correlation has yet to be directly observed for a tryptophan residue. In addition, the asymmetric indole ring might also lead to heterogeneity from {chi}{sup 2} rotations. In this paper, the time-resolved and steady-state fluorescence properties of (tryptophan{sup 2})oxytocin at pH 3 are presented and compared with {sup 1}H NMR results. According to the unrestricted analyses of individual fluorescence decay curves taken as a function of emission wavelength-independent decay constants, only three exponential terms aremore » required. In addition, the preexponential weighting factors (amplitudes) have the same relative relationship (weights) as the {sup 1}H NMR-determined {chi}{sup 1} rotamer populations of the indole side chain. {sup 15}N was used in heteronuclear coupling experiments to confirm the rotamer assignments. Inclusion of a linked function restricting the decay amplitudes to the {chi}{sup 1} rotamer populations in the individual decay curve analyses and in the global analysis confirms this correlation. According to qualitative nuclear Overhauser data, there are two {chi}{sup 2} populations.« less

Effect of filter type on the statistics of energy transfer between resolved and subfilter scales from a-priori analysis of direct numerical simulations of isotropic turbulence

NASA Astrophysics Data System (ADS)

Buzzicotti, M.; Linkmann, M.; Aluie, H.; Biferale, L.; Brasseur, J.; Meneveau, C.

2018-02-01

The effects of different filtering strategies on the statistical properties of the resolved-to-subfilter scale (SFS) energy transfer are analysed in forced homogeneous and isotropic turbulence. We carry out a-priori analyses of the statistical characteristics of SFS energy transfer by filtering data obtained from direct numerical simulations with up to 20483 grid points as a function of the filter cutoff scale. In order to quantify the dependence of extreme events and anomalous scaling on the filter, we compare a sharp Fourier Galerkin projector, a Gaussian filter and a novel class of Galerkin projectors with non-sharp spectral filter profiles. Of interest is the importance of Galilean invariance and we confirm that local SFS energy transfer displays intermittency scaling in both skewness and flatness as a function of the cutoff scale. Furthermore, we quantify the robustness of scaling as a function of the filtering type.

Self-propagated combustion synthesis of few-layered graphene: an optical properties perspective.

PubMed

Mohandoss, Manonmani; Sen Gupta, Soujit; Kumar, Ramesh; Islam, Md Rabiul; Som, Anirban; Mohd, Azhardin Ganayee; Pradeep, T; Maliyekkal, Shihabudheen M

2018-04-26

This paper describes a labour efficient and cost-effective strategy to prepare few-layered of reduced graphene oxide like (RGOL) sheets from graphite. The self-propagated combustion route enables the bulk production of RGOL sheets. Microscopic and spectroscopic analyses confirmed the formation of few-layer graphene sheets of an average thickness of ∼3 nm and the presence of some oxygen functional groups with a C/O ratio of 8.74. A possible mechanistic pathway for the formation of RGOL sheets is proposed. The optical properties of the RGOL sample were studied in detail by means of Spectroscopic Ellipsometry (SE). The experimental abilities of SE in relating the optical properties with the number of oxygen functionalities present in the samples are explored. The data were analysed by a double-layered optical model along with the Drude-Lorentz oscillatory dispersion relation. The refractive index (n = 2.24), extinction coefficient (k = 2.03), and dielectric functions are obtained using point-by-point analysis and are also checked for Kramers-Kronig (KK) consistency.

The AMINO experiment: exposure of amino acids in the EXPOSE-R experiment on the International Space Station and in laboratory

NASA Astrophysics Data System (ADS)

Bertrand, Marylène; Chabin, Annie; Colas, Cyril; Cadène, Martine; Chaput, Didier; Brack, Andre; Cottin, Herve

2015-01-01

In order to confirm the results of previous experiments concerning the chemical behaviour of organic molecules in the space environment, organic molecules (amino acids and a dipeptide) in pure form and embedded in meteorite powder were exposed in the AMINO experiment in the EXPOSE-R facility onboard the International Space Station. After exposure to space conditions for 24 months (2843 h of irradiation), the samples were returned to the Earth and analysed in the laboratory for reactions caused by solar ultraviolet (UV) and other electromagnetic radiation. Laboratory UV exposure was carried out in parallel in the Cologne DLR Center (Deutsches Zentrum für Luft und Raumfahrt). The molecules were extracted from the sample holder and then (1) derivatized by silylation and analysed by gas chromatography coupled to a mass spectrometer (GC-MS) in order to quantify the rate of degradation of the compounds and (2) analysed by high-resolution mass spectrometry (HRMS) in order to understand the chemical reactions that occurred. The GC-MS results confirm that resistance to irradiation is a function of the chemical nature of the exposed molecules and of the wavelengths of the UV light. They also confirm the protective effect of a coating of meteorite powder. The most altered compounds were the dipeptides and aspartic acid while the most robust were compounds with a hydrocarbon chain. The MS analyses document the products of reactions, such as decarboxylation and decarbonylation of aspartic acid, taking place after UV exposure. Given the universality of chemistry in space, our results have a broader implication for the fate of organic molecules that seeded the planets as soon as they became habitable as well as for the effects of UV radiation on exposed molecules at the surface of Mars, for example.

Green's function integral equation method for propagation of electromagnetic waves in an anisotropic dielectric-magnetic slab

NASA Astrophysics Data System (ADS)

Shu, Weixing; Lv, Xiaofang; Luo, Hailu; Wen, Shuangchun

2010-08-01

We extend the Green's function integral method to investigate the propagation of electromagnetic waves through an anisotropic dielectric-magnetic slab. From a microscopic perspective, we analyze the interaction of wave with the slab and derive the propagation characteristics by self-consistent analyses. Applying the results, we find an alternative explanation to the general mechanism for the photon tunneling. The results are confirmed by numerical simulations and disclose the underlying physics of wave propagation through slab. The method extended is applicable to other problems of propagation in dielectric-magnetic materials, including metamaterials.

Nanofilter platform based on functionalized carbon nanotubes for adsorption and elimination of Acrolein, a toxicant in cigarette smoke

NASA Astrophysics Data System (ADS)

Yoosefian, Mehdi; Pakpour, Atef; Etminan, Nazanin

2018-06-01

This paper discusses the use of carboxylated single-walled carbon nanotube as a general nanofilter platform for the removal of acrolein carcinogen from cigarette smoke. The analyses carried out in the detailed study of the electronic and structural effects of the adsorption of acrolein onto COOH loaded on single-walled carbon nanotube under the density functional theory framework. The results of Bader theory of atoms in molecules, natural bond orbital, molecular potential electron surface and density of state confirm the potential application of the suggested nanofilter platform.

The effect of nanofiber based filter morphology on bacteria deactivation during water filtration

NASA Astrophysics Data System (ADS)

Kimmer, Dusan; Vincent, Ivo; Lev, Jaroslav; Kalhotka, Libor; Mikula, Premysl; Korinkova, Radka; Sambaer, Wannes; Zatloukal, Martin

2013-04-01

Procedures permitting to prepare homogeneous functionalized nanofibre structures based on polyurethanes modified by phthalocyanines (PCs) by employing a suitable combination of variables during the electrospinning process are presented. Compared are filtration and bacteria deactivation properties of open and planar nanostructures with PCs embedded into polyurethane chain by a covalent bond protecting the release of active organic compound during the filtration process. Finding that the morphology of functionalized nanofibre structures have an effect on bacterial growth was confirmed by microbiological and physico-chemical analyses, such as the inoculation in a nutrient agar culture medium and flow cytometry.

Chiral 1,2- and 1,3-diol-functionalized chromophores as Lego building blocks for coupled structures.

PubMed

Spange, Stefan; Hofmann, Katja; Walfort, Bernhard; Rüffer, Tobias; Lang, Heinrich

2005-10-14

Chiral nitroanilines containing 1,2- or 1,3-diol functionalities have been synthesized by nucleophilic aromatic substitution of fluoronitroanilines with 1-aminopropane-2,3-diols and 2-aminopropane-1,3-diol in the melt. X-ray structure analyses confirm retention of the configuration of the chiral center. The novel chromophores are suitable to link reversibly to various substituted arylboronic acids which allows the construction of new solvatochromic sensor molecules suitable to response to solvent and anion coordination by fluoride. The solvatochromism of the new compounds has been studied using the Kamlet-Taft LSE relationship.

Subcellular localization of celery mannitol dehydrogenase. A cytosolic metabolic enzyme in nuclei.

PubMed Central

Yamamoto, Y T; Zamski, E; Williamson, J D; Conkling, M A; Pharr, D M

1997-01-01

Mannitol dehydrogenase (MTD) is the first enzyme in mannitol catabolism in celery (Apium graveolens L. var dulce [Mill] Pers. cv Florida 638). Mannitol is an important photoassimilate, as well as providing plants with resistance to salt and osmotic stress. Previous work has shown that expression of the celery Mtd gene is regulated by many factors, such as hexose sugars, salt and osmotic stress, and salicylic acid. Furthermore, MTD is present in cells of sink organs, phloem cells, and mannitol-grown suspension cultures. Immunogold localization and biochemical analyses presented here demonstrate that celery MTD is localized in the cytosol and nuclei. Although the cellular density of MTD varies among different cell types, densities of nuclear and cytosolic MTD in a given cell are approximately equal. Biochemical analyses of nuclear extracts from mannitol-grown cultured cells confirmed that the nuclear-localized MTD is enzymatically active. The function(s) of nuclear-localized MTD is unknown. PMID:9414553

Determination and interpretation of the optical constants for solar cell materials

NASA Astrophysics Data System (ADS)

Fujiwara, Hiroyuki; Fujimoto, Shohei; Tamakoshi, Masato; Kato, Masato; Kadowaki, Hideyuki; Miyadera, Tetsuhiko; Tampo, Hitoshi; Chikamatsu, Masayuki; Shibata, Hajime

2017-11-01

Solar cell materials in thin film form often exhibit quite rough surface, which makes the accurate determination of the optical constants using spectroscopic ellipsometry (SE) quite difficult. In this study, we investigate the effect of the rough surface on the SE analysis and establish an analysis procedure, which is quite helpful for the correction of the underestimated roughness contribution. As examples, the roughness analyses for CuInSe2 and CH3NH3PbI3 hybrid-perovskite thin films are presented. Moreover, to interpret the dielectric functions of emerging solar cell materials, such as CH3NH3PbI3 and Cu2ZnSnSe4, the optical transition analyses are performed based on density functional theory (DFT). The excellent agreement observed between the experimental and DFT results allows the detailed assignment of the transition peaks, confirming the importance of DFT for revealing fundamental optical characteristics.

Negative regulation of ABA signaling by WRKY33 is critical for Arabidopsis immunity towards Botrytis cinerea 2100

PubMed Central

Liu, Shouan; Kracher, Barbara; Ziegler, Jörg; Birkenbihl, Rainer P; Somssich, Imre E

2015-01-01

The Arabidopsis mutant wrky33 is highly susceptible to Botrytis cinerea. We identified >1680 Botrytis-induced WRKY33 binding sites associated with 1576 Arabidopsis genes. Transcriptional profiling defined 318 functional direct target genes at 14 hr post inoculation. Comparative analyses revealed that WRKY33 possesses dual functionality acting either as a repressor or as an activator in a promoter-context dependent manner. We confirmed known WRKY33 targets involved in hormone signaling and phytoalexin biosynthesis, but also uncovered a novel negative role of abscisic acid (ABA) in resistance towards B. cinerea 2100. The ABA biosynthesis genes NCED3 and NCED5 were identified as direct targets required for WRKY33-mediated resistance. Loss-of-WRKY33 function resulted in elevated ABA levels and genetic studies confirmed that WRKY33 acts upstream of NCED3/NCED5 to negatively regulate ABA biosynthesis. This study provides the first detailed view of the genome-wide contribution of a specific plant transcription factor in modulating the transcriptional network associated with plant immunity. DOI: http://dx.doi.org/10.7554/eLife.07295.001 PMID:26076231

Differential Adjustment Among Rural Adolescents Exposed to Family Violence.

PubMed

Sianko, Natallia; Hedge, Jasmine M; McDonell, James R

2016-04-22

This study examines differences in psychological adjustment in a sample of rural adolescents who have been exposed to family violence. Self-report questionnaires were administered to 580 adolescents and their primary caregivers. The results revealed that over two thirds of the study participants (68.8%) had been exposed to violence in their families. As hypothesized, cluster analysis identified several profiles among adolescents, distinguished by their psychological and emotional functioning: well adjusted (46.2%), moderately adjusted (44.3%), and struggling (9.5%). Discriminant function analysis confirmed the groupings and revealed that family functioning was among the most influential factors explaining adjustment differences. Multivariate analyses of variance (MANOVAs) further showed that adolescents from each of the three adjustment profiles reported significantly different levels of family social support, parental involvement, and perceived neighborhood safety. Overall, the results confirm heterogeneity of adolescent adaptation in the aftermath of family violence and provide insights into family and neighborhood factors that account for variability in adolescents' reactions to violence. Implications for future research and practical interventions are discussed. © The Author(s) 2016.

Stuttering, induced fluency, and natural fluency: a hierarchical series of activation likelihood estimation meta-analyses.

PubMed

Budde, Kristin S; Barron, Daniel S; Fox, Peter T

2014-12-01

Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). Copyright © 2014 Elsevier Inc. All rights reserved.

Reminiscence Therapy Improves Cognitive Functions and Reduces Depressive Symptoms in Elderly People With Dementia: A Meta-Analysis of Randomized Controlled Trials.

PubMed

Huang, Hui-Chuan; Chen, Yu-Ting; Chen, Pin-Yuan; Huey-Lan Hu, Sophia; Liu, Fang; Kuo, Ying-Ling; Chiu, Hsiao-Yean

2015-12-01

Cognitive function impairments and depressive symptoms are common in elderly people with dementia. Previous meta-analyses of outdated and small-scale studies have reported inconsistent results regarding the effects of reminiscence therapy on cognitive functions and depressive symptoms; therefore, we conducted a meta-analysis by including more recent randomized controlled trials (RCTs) with large sample sizes to investigate the immediate and long-term (6-10 months) effects of reminiscence therapy on cognitive functions and depressive symptoms in elderly people with dementia. Electronic databases, including PubMed, Medline, CINAHL, PsycINFO, the Cochrane Central Register of Controlled Trials, ProQuest, Google Scholar, and Chinese databases were searched to select eligible articles. Primary outcome measures included the scores of cognitive functions and depressive symptoms. In total, 12 RCT studies investigating the effects of reminiscence therapy on cognitive functions and depressive symptoms in elderly people with dementia were included. Two reviewers independently extracted data. All analyses were performed using a random-effects model. Reminiscence therapy had a small-size effect on cognitive functions (g = 0.18, 95% confidence interval [CI] 0.05-0.30) and a moderate-size effect on depressive symptoms (g = -0.49, 95% CI -0.70 to -0.28) in elderly people with dementia. Long-term effects of reminiscence therapy on cognitive functions and depressive symptoms were not confirmed. Moderator analysis revealed that institutionalized elderly people with dementia exhibited greater improvement in depressive symptoms than community-dwelling people with dementia did (g = -0.59 vs. -0.16, P = .003). This meta-analysis confirms that reminiscence therapy is effective in improving cognitive functions and depressive symptoms in elderly people with dementia. Our findings suggest that regular reminiscence therapy should be considered for inclusion as routine care for the improvement of cognitive functions and depressive symptoms in elderly people with dementia, particularly in institutionalized residents with dementia. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Immobilization Effect of Morphological, Thermal and Optical Properties in Biotemplate on Zinc Oxide Nanocomposite from Chitosan

NASA Astrophysics Data System (ADS)

Karpuraranjith, M.; Thambidurai, S.

Biotemplate-based zinc oxide nanocomposite was effectively prepared via simple chemical precipitation route. The functional groups of amino (-NH2), hydroxyl (-OH) and O-Zn-O were confirmed and characterized by FTIR spectroscopy. The structural and morphological properties were confirmed by XRD, UV-Vis DRS, HR-SEM and TEM analyses. The elemental composition of carbon, nitrogen, zinc and oxygen was confirmed by energy-dispersive X-ray analysis (EDAX) and Brunauer-Emmett-Teller high surface area of materials was estimated to be 52.49m2/g, respectively. Thermogravimetric analysis (TGA) shows that biotemplate on zinc oxide nanocomposite has higher thermal stability than chitosan matrix. The results demonstrate that biotemplate on zinc oxide matrix causes immobilization effect among the two components. Therefore, chitosan-ZnO nanocomposite has a microcrystalline morphological structure and also good thermal stability, so it can be a promising material for sensors, medical, tissue engineering and wastewater treatment applications.

GAT: a graph-theoretical analysis toolbox for analyzing between-group differences in large-scale structural and functional brain networks.

PubMed

Hosseini, S M Hadi; Hoeft, Fumiko; Kesler, Shelli R

2012-01-01

In recent years, graph theoretical analyses of neuroimaging data have increased our understanding of the organization of large-scale structural and functional brain networks. However, tools for pipeline application of graph theory for analyzing topology of brain networks is still lacking. In this report, we describe the development of a graph-analysis toolbox (GAT) that facilitates analysis and comparison of structural and functional network brain networks. GAT provides a graphical user interface (GUI) that facilitates construction and analysis of brain networks, comparison of regional and global topological properties between networks, analysis of network hub and modules, and analysis of resilience of the networks to random failure and targeted attacks. Area under a curve (AUC) and functional data analyses (FDA), in conjunction with permutation testing, is employed for testing the differences in network topologies; analyses that are less sensitive to the thresholding process. We demonstrated the capabilities of GAT by investigating the differences in the organization of regional gray-matter correlation networks in survivors of acute lymphoblastic leukemia (ALL) and healthy matched Controls (CON). The results revealed an alteration in small-world characteristics of the brain networks in the ALL survivors; an observation that confirm our hypothesis suggesting widespread neurobiological injury in ALL survivors. Along with demonstration of the capabilities of the GAT, this is the first report of altered large-scale structural brain networks in ALL survivors.

Experimental and density functional theory (DFT): A dual approach to probe the key properties of creatininium L-tartrate monohydrate single crystal for nonlinear optical applications

NASA Astrophysics Data System (ADS)

Thirumurugan, R.; Babu, B.; Anitha, K.; Chandrasekaran, J.

2017-12-01

A novel organic nonlinear optical (NLO) material, creatininium L-tartrate monohydrate (CTM) was synthesized and it was grown as single crystals with optical quality. 1H and 13C NMR spectral studies were performed and molecular structure of synthesized CTM compound was confirmed. Single crystal X-ray diffraction (SXRD) analysis confirmed that CTM was crystallized in orthorhombic system with non-centrosymmetric (NCS), P212121, space group. The grown crystal exhibited admirable properties such as second harmonic generation efficiency (SHG) (1.9 times KDP), and high laser damage threshold (LDT) value of 3.7 GW cm-2. CTM crystal displayed high transparency (∼60%) in the visible and near-IR region with low cut-off wavelength at 249 nm. Photoluminescence study confirmed blue wavelength emission (∼463 nm) of grown crystal. Thermal and mechanical behaviours have been successfully analysed for grown crystals. The dielectric studies were carried out for grown crystal as a function of frequencies at different temperatures. Hirshfeld surface and fingerprint plots provided the percentage of individual interactions contributed by each atom. Moreover, density functional theory (DFT) calculations have been employed to probe the frontier molecular orbitals (FMOs) and first hyperpolarizability (β) analysis of the optimized CTM structure. These results validated CTM as a suitable NLO candidate and were discussed in this work.

Synthesis, characterization and magnetic property of maghemite (γ-Fe{sub 2}O{sub 3}) nanoparticles and their protective coating with pepsin for bio-functionalization

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

Bandhu, A.; Sutradhar, S.; Mukherjee, S.

Highlights: • Maghemite nanoparticles were prepared by a modified co-precipitation method. • Nanoparticles were then successfully coated with pepsin for bio-functionlization. • XRD and Mössbauer spectra confirmed the maghemite phase of the nanoparticles. • Magnetic data were analysed to evaluate particle size, anisotropy etc. - Abstract: Maghemite nanoparticles (γ-Fe{sub 2}O{sub 3}) are prepared by co-precipitation method. To obtain bio-functionalized magnetic nanoparticles for magnetically controlled drug delivery, the prepared nanoparticles are successfully coated with pepsin, a bio-compatible polymer and digestive enzyme. Crystallographic phase of the nanoparticles is confirmed by X-ray diffractograms (XRD), high resolution transmission electron microscopy (HRTEM) and {sup 57}Femore » Mössbauer spectrometry. The average size of nanoparticles/nanocrystallites is estimated from the (3 1 1) peak of the XRD pattern using Debye–Scherrer formula. Results of HRTEM of coated and bare samples are in good agreement with those extracted from the XRD analysis. The dynamic magnetic properties are observed and different quantities viz., coercive field, magnetization, remanence, hysteresis losses etc., are estimated, which confirmed the presence of superparamagnetic relaxation of nanoparticles. Mössbauer spectra of the samples recorded at both 300 and 77 K, confirmed that the majority of particles are maghemite together with a very small fraction of magnetite nanoparticles.« less

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.

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways.

PubMed

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian'an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O'Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tõnu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-09-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.

Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways

PubMed Central

Scott, Robert A; Lagou, Vasiliki; Welch, Ryan P; Wheeler, Eleanor; Montasser, May E; Luan, Jian’an; Mägi, Reedik; Strawbridge, Rona J; Rehnberg, Emil; Gustafsson, Stefan; Kanoni, Stavroula; Rasmussen-Torvik, Laura J; Yengo, Loïc; Lecoeur, Cecile; Shungin, Dmitry; Sanna, Serena; Sidore, Carlo; Johnson, Paul C D; Jukema, J Wouter; Johnson, Toby; Mahajan, Anubha; Verweij, Niek; Thorleifsson, Gudmar; Hottenga, Jouke-Jan; Shah, Sonia; Smith, Albert V; Sennblad, Bengt; Gieger, Christian; Salo, Perttu; Perola, Markus; Timpson, Nicholas J; Evans, David M; Pourcain, Beate St; Wu, Ying; Andrews, Jeanette S; Hui, Jennie; Bielak, Lawrence F; Zhao, Wei; Horikoshi, Momoko; Navarro, Pau; Isaacs, Aaron; O’Connell, Jeffrey R; Stirrups, Kathleen; Vitart, Veronique; Hayward, Caroline; Esko, Tönu; Mihailov, Evelin; Fraser, Ross M; Fall, Tove; Voight, Benjamin F; Raychaudhuri, Soumya; Chen, Han; Lindgren, Cecilia M; Morris, Andrew P; Rayner, Nigel W; Robertson, Neil; Rybin, Denis; Liu, Ching-Ti; Beckmann, Jacques S; Willems, Sara M; Chines, Peter S; Jackson, Anne U; Kang, Hyun Min; Stringham, Heather M; Song, Kijoung; Tanaka, Toshiko; Peden, John F; Goel, Anuj; Hicks, Andrew A; An, Ping; Müller-Nurasyid, Martina; Franco-Cereceda, Anders; Folkersen, Lasse; Marullo, Letizia; Jansen, Hanneke; Oldehinkel, Albertine J; Bruinenberg, Marcel; Pankow, James S; North, Kari E; Forouhi, Nita G; Loos, Ruth J F; Edkins, Sarah; Varga, Tibor V; Hallmans, Göran; Oksa, Heikki; Antonella, Mulas; Nagaraja, Ramaiah; Trompet, Stella; Ford, Ian; Bakker, Stephan J L; Kong, Augustine; Kumari, Meena; Gigante, Bruna; Herder, Christian; Munroe, Patricia B; Caulfield, Mark; Antti, Jula; Mangino, Massimo; Small, Kerrin; Miljkovic, Iva; Liu, Yongmei; Atalay, Mustafa; Kiess, Wieland; James, Alan L; Rivadeneira, Fernando; Uitterlinden, Andre G; Palmer, Colin N A; Doney, Alex S F; Willemsen, Gonneke; Smit, Johannes H; Campbell, Susan; Polasek, Ozren; Bonnycastle, Lori L; Hercberg, Serge; Dimitriou, Maria; Bolton, Jennifer L; Fowkes, Gerard R; Kovacs, Peter; Lindström, Jaana; Zemunik, Tatijana; Bandinelli, Stefania; Wild, Sarah H; Basart, Hanneke V; Rathmann, Wolfgang; Grallert, Harald; Maerz, Winfried; Kleber, Marcus E; Boehm, Bernhard O; Peters, Annette; Pramstaller, Peter P; Province, Michael A; Borecki, Ingrid B; Hastie, Nicholas D; Rudan, Igor; Campbell, Harry; Watkins, Hugh; Farrall, Martin; Stumvoll, Michael; Ferrucci, Luigi; Waterworth, Dawn M; Bergman, Richard N; Collins, Francis S; Tuomilehto, Jaakko; Watanabe, Richard M; de Geus, Eco J C; Penninx, Brenda W; Hofman, Albert; Oostra, Ben A; Psaty, Bruce M; Vollenweider, Peter; Wilson, James F; Wright, Alan F; Hovingh, G Kees; Metspalu, Andres; Uusitupa, Matti; Magnusson, Patrik K E; Kyvik, Kirsten O; Kaprio, Jaakko; Price, Jackie F; Dedoussis, George V; Deloukas, Panos; Meneton, Pierre; Lind, Lars; Boehnke, Michael; Shuldiner, Alan R; van Duijn, Cornelia M; Morris, Andrew D; Toenjes, Anke; Peyser, Patricia A; Beilby, John P; Körner, Antje; Kuusisto, Johanna; Laakso, Markku; Bornstein, Stefan R; Schwarz, Peter E H; Lakka, Timo A; Rauramaa, Rainer; Adair, Linda S; Smith, George Davey; Spector, Tim D; Illig, Thomas; de Faire, Ulf; Hamsten, Anders; Gudnason, Vilmundur; Kivimaki, Mika; Hingorani, Aroon; Keinanen-Kiukaanniemi, Sirkka M; Saaristo, Timo E; Boomsma, Dorret I; Stefansson, Kari; van der Harst, Pim; Dupuis, Josée; Pedersen, Nancy L; Sattar, Naveed; Harris, Tamara B; Cucca, Francesco; Ripatti, Samuli; Salomaa, Veikko; Mohlke, Karen L; Balkau, Beverley; Froguel, Philippe; Pouta, Anneli; Jarvelin, Marjo-Riitta; Wareham, Nicholas J; Bouatia-Naji, Nabila; McCarthy, Mark I; Franks, Paul W; Meigs, James B; Teslovich, Tanya M; Florez, Jose C; Langenberg, Claudia; Ingelsson, Erik; Prokopenko, Inga; Barroso, Inês

2012-01-01

Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have raised the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional follow-up of these newly discovered loci will further improve our understanding of glycemic control. PMID:22885924

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.

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.

Structure and mechanism of the phage T4 recombination mediator protein UvsY

DOE PAGES

Gajewski, Stefan; Waddell, Michael Brett; Vaithiyalingam, Sivaraja; ...

2016-03-07

The UvsY recombination mediator protein is critical for efficient homologous recombination in bacteriophage T4 and is the functional analog of the eukaryotic Rad52 protein. During T4 homologous recombination, the UvsX recombinase has to compete with the prebound gp32 single-stranded binding protein for DNA-binding sites and UvsY stimulates this filament nucleation event. We report here the crystal structure of UvsY in four similar open-barrel heptameric assemblies and provide structural and biophysical insights into its function. The UvsY heptamer was confirmed in solution by centrifugation and light scattering, and thermodynamic analyses revealed that the UvsY–ssDNA interaction occurs within the assembly via twomore » distinct binding modes. Using surface plasmon resonance, we also examined the binding of UvsY to both ssDNA and the ssDNA–gp32 complex. These analyses confirmed that ssDNA can bind UvsY and gp32 independently and also as a ternary complex. They also showed that residues located on the rim of the heptamer are required for optimal binding to ssDNA, thus identifying the putative ssDNA-binding surface. We propose a model in which UvsY promotes a helical ssDNA conformation that disfavors the binding of gp32 and initiates the assembly of the ssDNA–UvsX filament.« less

Genomics and expression profiles of the Hedgehog and Notch signaling pathways in sea urchin development.

PubMed

Walton, Katherine D; Croce, Jenifer C; Glenn, Thomas D; Wu, Shu-Yu; McClay, David R

2006-12-01

The Hedgehog (Hh) and Notch signal transduction pathways control a variety of developmental processes including cell fate choice, differentiation, proliferation, patterning and boundary formation. Because many components of these pathways are conserved, it was predicted and confirmed that pathway components are largely intact in the sea urchin genome. Spatial and temporal location of these pathways in the embryo, and their function in development offer added insight into their mechanistic contributions. Accordingly, all major components of both pathways were identified and annotated in the sea urchin Strongylocentrotus purpuratus genome and the embryonic expression of key components was explored. Relationships of the pathway components, and modifiers predicted from the annotation of S. purpuratus, were compared against cnidarians, arthropods, urochordates, and vertebrates. These analyses support the prediction that the pathways are highly conserved through metazoan evolution. Further, the location of these two pathways appears to be conserved among deuterostomes, and in the case of Notch at least, display similar capacities in endomesoderm gene regulatory networks. RNA expression profiles by quantitative PCR and RNA in situ hybridization reveal that Hedgehog is produced by the endoderm beginning just prior to invagination, and signals to the secondary mesenchyme-derived tissues at least until the pluteus larva stage. RNA in situ hybridization of Notch pathway members confirms that Notch functions sequentially in the vegetal-most secondary mesenchyme cells and later in the endoderm. Functional analyses in future studies will embed these pathways into the growing knowledge of gene regulatory networks that govern early specification and morphogenesis.

Genomic and Coexpression Analyses Predict Multiple Genes Involved in Triterpene Saponin Biosynthesis in Medicago truncatula[C][W

PubMed Central

Naoumkina, Marina A.; Modolo, Luzia V.; Huhman, David V.; Urbanczyk-Wochniak, Ewa; Tang, Yuhong; Sumner, Lloyd W.; Dixon, Richard A.

2010-01-01

Saponins, an important group of bioactive plant natural products, are glycosides of triterpenoid or steroidal aglycones (sapogenins). Saponins possess many biological activities, including conferring potential health benefits for humans. However, most of the steps specific for the biosynthesis of triterpene saponins remain uncharacterized at the molecular level. Here, we use comprehensive gene expression clustering analysis to identify candidate genes involved in the elaboration, hydroxylation, and glycosylation of the triterpene skeleton in the model legume Medicago truncatula. Four candidate uridine diphosphate glycosyltransferases were expressed in Escherichia coli, one of which (UGT73F3) showed specificity for multiple sapogenins and was confirmed to glucosylate hederagenin at the C28 position. Genetic loss-of-function studies in M. truncatula confirmed the in vivo function of UGT73F3 in saponin biosynthesis. This report provides a basis for future studies to define genetically the roles of multiple cytochromes P450 and glycosyltransferases in triterpene saponin biosynthesis in Medicago. PMID:20348429

Soil functional diversity analysis of a bauxite-mined restoration chronosequence.

PubMed

Lewis, Dawn E; White, John R; Wafula, Denis; Athar, Rana; Dickerson, Tamar; Williams, Henry N; Chauhan, Ashvini

2010-05-01

Soil microorganisms are sensitive to environmental perturbations such that changes in microbial community structure and function can provide early signs of anthropogenic disturbances and even predict restoration success. We evaluated the bacterial functional diversity of un-mined and three chronosequence sites at various stages of rehabilitation (0, 10, and 20 years old) located in the Mocho Mountains of Jamaica. Samples were collected during the dry and wet seasons and analyzed for metal concentrations, microbial biomass carbon, bacterial numbers, and functional responses of soil microbiota using community-level physiological profile (CLPP) assays. Regardless of the season, un-mined soils consisted of higher microbial biomass and numbers than any of the rehabilitated sites. Additionally, the number and rate of substrates utilized and substrate evenness (the distribution of color development between the substrates) were significantly greater in the un-mined soils with carbohydrates being preferentially utilized than amino acids, polymers, carboxylic acids, and esters. To some extent, functional responses varied with the seasons but the least physiological activity was shown by the site rehabilitated in 1987 indicating long-term perturbation to this ecosystem. Small subunit ribosomal DNA (SSUrDNA)-denaturing gradient-gel electrophoresis analyses on the microbiota collected from the most preferred CLPP substrates followed by taxonomic analyses showed Proteobacteria, specifically the gamma-proteobacteria, as the most functionally active phyla, indicating a propensity of this phyla to out-compete other groups under the prevailing conditions. Additionally, multivariate statistical analyses, Shannon's diversity, and evenness indices, principal component analysis, biplot and un-weighted-pair-group method with arithmetic averages dendrograms further confirmed that un-mined sites were distinctly different from the rehabilitated soils.

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

Engineering the work function of buckled boron α-sheet by lithium adsorption: a first-principles investigation.

PubMed

Zheng, Bing; Yu, Hai-tao; Xie, Ying; Lian, Yong-fu

2014-11-26

First-principles density functional theory calculations were performed to study the effect of Li adsorption on the structural and electronic properties, particularly the work function, of boron α-sheet. The calculated binding energies indicated that boron α-sheet could be well stabilized by the adsorption of Li atoms. Furthermore, the work functions of Li-adsorbed boron α-sheets were observed to decrease drastically with increasing Li coverage. The work functions are lower than that of Mg and even, for some of them, lower than that of Ca, indicating a considerable potential application of Li-adsorbed boron α-sheets as field-emission and electrode materials. Based on the calculated geometric and electronic structures, we discuss in details some possible aspects affecting the work function. The Li coverage dependence of the work functions of Li-adsorbed boron α-sheets was further confirmed by electrostatic potential analyses. The relationship between the work function variation and the Fermi and vacuum energy level shifts was also discussed, and we observed that the variation of the work function is primarily associated with the shift of the Fermi energy level. It is the surface dipole formed by the interaction between adatoms and substrate that should be responsible for the observed variation of the work function, whereas the increasing negative charge and rumpling for boron α-sheet only play minor roles. Additionally, the effect of Li adatoms on the work function of boron α-sheet was confirmed to be much stronger than that of graphene or a graphene double layer.

Trends and variability of cloud fraction cover in the Arctic, 1982-2009

NASA Astrophysics Data System (ADS)

Boccolari, Mauro; Parmiggiani, Flavio

2018-05-01

Climatology, trends and variability of cloud fraction cover (CFC) data over the Arctic (north of 70°N), were analysed over the 1982-2009 period. Data, available from the Climate Monitoring Satellite Application Facility (CM SAF), are derived from satellite measurements by AVHRR. Climatological means confirm permanent high CFC values over the Atlantic sector during all the year and during summer over the eastern Arctic Ocean. Lower values are found in the rest of the analysed area especially over Greenland and the Canadian Archipelago, nearly continuously during all the months. These results are confirmed by CFC trends and variability. Statistically significant trends were found during all the months over the Greenland Sea, particularly during the winter season (negative, less than -5 % dec -1) and over the Beaufort Sea in spring (positive, more than +5 % dec -1). CFC variability, investigated by the Empirical Orthogonal Functions, shows a substantial "non-variability" in the Northern Atlantic Ocean. Statistically significant correlations between CFC principal components elements and both the Pacific Decadal Oscillation index and Pacific North America patterns are found.

Selective O 2 Sorption at Ambient Temperatures via Node Distortions in Sc-MIL-100

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

Sava Gallis, Dorina F.; Chapman, Karena W.; Rodriguez, Mark A.

2016-05-24

An open pored metal–organic framework (MOF) with oxygen selectivity at exceptionally high temperatures is confirmed by synthesis, sorption, and synchrotron structural analyses. The large-pore MIL-100 framework with access to the metal center (e.g., Sc and Fe) resulted in preferential O2 over N2 gas uptake at temperatures ranging from 77 K to ambient temperatures (258, 298, and 313 K). Most notably, Sc-MIL-100 shows exceptional O2 sorption; pair distribution function analyses indicate that this is due to distortions in the framework owing to the size of Sc atoms, in particular in the trimer metal cluster. Experimental studies also correlate very well withmore » GCMC simulations, confirming more favorable O2-framework interactions at pressures up to 1 bar, due to the close proximity of O2 to the high density of metal centers in the small tetrahedral cages. Both materials maintain their crystallinity upon gas adsorption cycling, are regenerable, and show exceptional promise for use in energy efficient oxygen purification processes, such as Pressure Swing Adsorption.« less

Discovery of new enzymes and metabolic pathways by using structure and genome context.

PubMed

Zhao, Suwen; Kumar, Ritesh; Sakai, Ayano; Vetting, Matthew W; Wood, B McKay; Brown, Shoshana; Bonanno, Jeffery B; Hillerich, Brandan S; Seidel, Ronald D; Babbitt, Patricia C; Almo, Steven C; Sweedler, Jonathan V; Gerlt, John A; Cronan, John E; Jacobson, Matthew P

2013-10-31

Assigning valid functions to proteins identified in genome projects is challenging: overprediction and database annotation errors are the principal concerns. We and others are developing computation-guided strategies for functional discovery with 'metabolite docking' to experimentally derived or homology-based three-dimensional structures. Bacterial metabolic pathways often are encoded by 'genome neighbourhoods' (gene clusters and/or operons), which can provide important clues for functional assignment. We recently demonstrated the synergy of docking and pathway context by 'predicting' the intermediates in the glycolytic pathway in Escherichia coli. Metabolite docking to multiple binding proteins and enzymes in the same pathway increases the reliability of in silico predictions of substrate specificities because the pathway intermediates are structurally similar. Here we report that structure-guided approaches for predicting the substrate specificities of several enzymes encoded by a bacterial gene cluster allowed the correct prediction of the in vitro activity of a structurally characterized enzyme of unknown function (PDB 2PMQ), 2-epimerization of trans-4-hydroxy-L-proline betaine (tHyp-B) and cis-4-hydroxy-D-proline betaine (cHyp-B), and also the correct identification of the catabolic pathway in which Hyp-B 2-epimerase participates. The substrate-liganded pose predicted by virtual library screening (docking) was confirmed experimentally. The enzymatic activities in the predicted pathway were confirmed by in vitro assays and genetic analyses; the intermediates were identified by metabolomics; and repression of the genes encoding the pathway by high salt concentrations was established by transcriptomics, confirming the osmolyte role of tHyp-B. This study establishes the utility of structure-guided functional predictions to enable the discovery of new metabolic pathways.

Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs)

PubMed Central

Dreyer, Ingo; Gomez-Porras, Judith Lucia; Riaño-Pachón, Diego Mauricio; Hedrich, Rainer; Geiger, Dietmar

2012-01-01

Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant) SLAC-like and 422 (402 non-redundant) ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general. PMID:23226151

Molecular Evolution of Slow and Quick Anion Channels (SLACs and QUACs/ALMTs).

PubMed

Dreyer, Ingo; Gomez-Porras, Judith Lucia; Riaño-Pachón, Diego Mauricio; Hedrich, Rainer; Geiger, Dietmar

2012-01-01

Electrophysiological analyses conducted about 25 years ago detected two types of anion channels in the plasma membrane of guard cells. One type of channel responds slowly to changes in membrane voltage while the other responds quickly. Consequently, they were named SLAC, for SLow Anion Channel, and QUAC, for QUick Anion Channel. Recently, genes SLAC1 and QUAC1/ALMT12, underlying the two different anion current components, could be identified in the model plant Arabidopsis thaliana. Expression of the gene products in Xenopus oocytes confirmed the quick and slow current kinetics. In this study we provide an overview on our current knowledge on slow and quick anion channels in plants and analyze the molecular evolution of ALMT/QUAC-like and SLAC-like channels. We discovered fingerprints that allow screening databases for these channel types and were able to identify 192 (177 non-redundant) SLAC-like and 422 (402 non-redundant) ALMT/QUAC-like proteins in the fully sequenced genomes of 32 plant species. Phylogenetic analyses provided new insights into the molecular evolution of these channel types. We also combined sequence alignment and clustering with predictions of protein features, leading to the identification of known conserved phosphorylation sites in SLAC1-like channels along with potential sites that have not been yet experimentally confirmed. Using a similar strategy to analyze the hydropathicity of ALMT/QUAC-like channels, we propose a modified topology with additional transmembrane regions that integrates structure and function of these membrane proteins. Our results suggest that cross-referencing phylogenetic analyses with position-specific protein properties and functional data could be a very powerful tool for genome research approaches in general.

Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency.

PubMed

Breitfeld, Jana; Martens, Susanne; Klammt, Jürgen; Schlicke, Marina; Pfäffle, Roland; Krause, Kerstin; Weidle, Kerstin; Schleinitz, Dorit; Stumvoll, Michael; Führer, Dagmar; Kovacs, Peter; Tönjes, Anke

2013-12-01

The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD. We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure. Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools. A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD.

Genetic analyses of bone morphogenetic protein 2, 4 and 7 in congenital combined pituitary hormone deficiency

PubMed Central

2013-01-01

Background The complex process of development of the pituitary gland is regulated by a number of signalling molecules and transcription factors. Mutations in these factors have been identified in rare cases of congenital hypopituitarism but for most subjects with combined pituitary hormone deficiency (CPHD) genetic causes are unknown. Bone morphogenetic proteins (BMPs) affect induction and growth of the pituitary primordium and thus represent plausible candidates for mutational screening of patients with CPHD. Methods We sequenced BMP2, 4 and 7 in 19 subjects with CPHD. For validation purposes, novel genetic variants were genotyped in 1046 healthy subjects. Additionally, potential functional relevance for most promising variants has been assessed by phylogenetic analyses and prediction of effects on protein structure. Results Sequencing revealed two novel variants and confirmed 30 previously known polymorphisms and mutations in BMP2, 4 and 7. Although phylogenetic analyses indicated that these variants map within strongly conserved gene regions, there was no direct support for their impact on protein structure when applying predictive bioinformatics tools. Conclusions A mutation in the BMP4 coding region resulting in an amino acid exchange (p.Arg300Pro) appeared most interesting among the identified variants. Further functional analyses are required to ultimately map the relevance of these novel variants in CPHD. PMID:24289245

Quantification of the impact of a confounding variable on functional connectivity confirms anti-correlated networks in the resting-state.

PubMed

Carbonell, F; Bellec, P; Shmuel, A

2014-02-01

The effect of regressing out the global average signal (GAS) in resting state fMRI data has become a concern for interpreting functional connectivity analyses. It is not clear whether the reported anti-correlations between the Default Mode and the Dorsal Attention Networks are intrinsic to the brain, or are artificially created by regressing out the GAS. Here we introduce a concept, Impact of the Global Average on Functional Connectivity (IGAFC), for quantifying the sensitivity of seed-based correlation analyses to the regression of the GAS. This voxel-wise IGAFC index is defined as the product of two correlation coefficients: the correlation between the GAS and the fMRI time course of a voxel, times the correlation between the GAS and the seed time course. This definition enables the calculation of a threshold at which the impact of regressing-out the GAS would be large enough to introduce spurious negative correlations. It also yields a post-hoc impact correction procedure via thresholding, which eliminates spurious correlations introduced by regressing out the GAS. In addition, we introduce an Artificial Negative Correlation Index (ANCI), defined as the absolute difference between the IGAFC index and the impact threshold. The ANCI allows a graded confidence scale for ranking voxels according to their likelihood of showing artificial correlations. By applying this method, we observed regions in the Default Mode and Dorsal Attention Networks that were anti-correlated. These findings confirm that the previously reported negative correlations between the Dorsal Attention and Default Mode Networks are intrinsic to the brain and not the result of statistical manipulations. Our proposed quantification of the impact that a confound may have on functional connectivity can be generalized to global effect estimators other than the GAS. It can be readily applied to other confounds, such as systemic physiological or head movement interferences, in order to quantify their impact on functional connectivity in the resting state. © 2013.

Age-Neutrality of a Brief Assessment of the Section III Alternative Model for Personality Disorders in Older Adults.

PubMed

Debast, Inge; Rossi, Gina; van Alphen, S P J

2018-04-01

The alternative model for personality disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders ( DSM-5) is considered an important step toward a possibly better conceptualization of personality pathology in older adulthood, by the introduction of levels of personality functioning (Criterion A) and trait dimensions (Criterion B). Our main aim was to examine age-neutrality of the Short Form of the Severity Indices of Personality Problems (SIPP-SF; Criterion A) and Personality Inventory for DSM-5-Brief Form (PID-5-BF; Criterion B). Differential item functioning (DIF) analyses and more specifically the impact on scale level through differential test functioning (DTF) analyses made clear that the SIPP-SF was more age-neutral (6% DIF, only one of four domains showed DTF) than the PID-5-BF (25% DIF, all four tested domains had DTF) in a community sample of older and younger adults. Age differences in convergent validity also point in the direction of differences in underlying constructs. Concurrent and criterion validity in geriatric psychiatry inpatients suggest that both the SIPP-SF scales measuring levels of personality functioning (especially self-functioning) and the PID-5-BF might be useful screening measures in older adults despite age-neutrality not being confirmed.

A combined computational-experimental analyses of selected metabolic enzymes in Pseudomonas species.

PubMed

Perumal, Deepak; Lim, Chu Sing; Chow, Vincent T K; Sakharkar, Kishore R; Sakharkar, Meena K

2008-09-10

Comparative genomic analysis has revolutionized our ability to predict the metabolic subsystems that occur in newly sequenced genomes, and to explore the functional roles of the set of genes within each subsystem. These computational predictions can considerably reduce the volume of experimental studies required to assess basic metabolic properties of multiple bacterial species. However, experimental validations are still required to resolve the apparent inconsistencies in the predictions by multiple resources. Here, we present combined computational-experimental analyses on eight completely sequenced Pseudomonas species. Comparative pathway analyses reveal that several pathways within the Pseudomonas species show high plasticity and versatility. Potential bypasses in 11 metabolic pathways were identified. We further confirmed the presence of the enzyme O-acetyl homoserine (thiol) lyase (EC: 2.5.1.49) in P. syringae pv. tomato that revealed inconsistent annotations in KEGG and in the recently published SYSTOMONAS database. These analyses connect and integrate systematic data generation, computational data interpretation, and experimental validation and represent a synergistic and powerful means for conducting biological research.

Unbiased transcriptomic analyses reveal distinct effects of immune deficiency in CNS function with and without injury.

PubMed

Luo, Dandan; Ge, Weihong; Hu, Xiao; Li, Chen; Lee, Chia-Ming; Zhou, Liqiang; Wu, Zhourui; Yu, Juehua; Lin, Sheng; Yu, Jing; Xu, Wei; Chen, Lei; Zhang, Chong; Jiang, Kun; Zhu, Xingfei; Li, Haotian; Gao, Xinpei; Geng, Yanan; Jing, Bo; Wang, Zhen; Zheng, Changhong; Zhu, Rongrong; Yan, Qiao; Lin, Quan; Ye, Keqiang; Sun, Yi E; Cheng, Liming

2018-06-28

The mammalian central nervous system (CNS) is considered an immune privileged system as it is separated from the periphery by the blood brain barrier (BBB). Yet, immune functions have been postulated to heavily influence the functional state of the CNS, especially after injury or during neurodegeneration. There is controversy regarding whether adaptive immune responses are beneficial or detrimental to CNS injury repair. In this study, we utilized immunocompromised SCID mice and subjected them to spinal cord injury (SCI). We analyzed motor function, electrophysiology, histochemistry, and performed unbiased RNA-sequencing. SCID mice displayed improved CNS functional recovery compared to WT mice after SCI. Weighted gene-coexpression network analysis (WGCNA) of spinal cord transcriptomes revealed that SCID mice had reduced expression of immune function-related genes and heightened expression of neural transmission-related genes after SCI, which was confirmed by immunohistochemical analysis and was consistent with better functional recovery. Transcriptomic analyses also indicated heightened expression of neurotransmission-related genes before injury in SCID mice, suggesting that a steady state of immune-deficiency potentially led to CNS hyper-connectivity. Consequently, SCID mice without injury demonstrated worse performance in Morris water maze test. Taken together, not only reduced inflammation after injury but also dampened steady-state immune function without injury heightened the neurotransmission program, resulting in better or worse behavioral outcomes respectively. This study revealed the intricate relationship between immune and nervous systems, raising the possibility for therapeutic manipulation of neural function via immune modulation.

Growth, structural, optical, mechanical and quantum chemical analysis of unidirectional grown bis(guanidinium) 5-sulfosalicylate (BGSSA) single crystal

NASA Astrophysics Data System (ADS)

Sreedevi, R.; Saravana Kumar, G.; Amarsingh Bhabu, K.; Balu, T.; Murugakoothan, P.; Rajasekaran, T. R.

2018-02-01

Bis(guanidinium) 5-sulfosalicylate single crystal was grown by using Sankaranarayanan-Ramasamy (SR) method from the solution of methanol and water in equimolar ratio. Good quality crystal with 50 mm length and 10 mm in diameter was grown. The grown crystal was subjected to single crystal X-ray diffraction analysis to confirm the crystal structure and it was found to be orthorhombic. UV-Vis-NIR spectroscopic study revealed that the SR method grown crystal had good optical transparency with wide optical band gap of 4.4 eV. The presence of the functional groups and modes of vibrations were identified by FTIR spectroscopy recorded in the range 4000-400 cm-1. The mechanical strength of the grown crystal was confirmed using Vickers microhardness tester by applying load from 25 g to 100 g. Density functional theory (DFT) method with B3LYP/6-31-G (d,p) level basis set was employed and hence the optimized molecular geometry, first order hyperpolarizability, dipole moment, thermodynamic functions, molecular electrostatic potential and frontier molecular orbital analysis of the grown BGSSA sample was computed and analysed.

Myeloid differentiation architecture of leukocyte transcriptome dynamics in perceived social isolation

PubMed Central

Cole, Steven W.; Capitanio, John P.; Chun, Katie; Arevalo, Jesusa M. G.; Ma, Jeffrey; Cacioppo, John T.

2015-01-01

To define the cellular mechanisms of up-regulated inflammatory gene expression and down-regulated antiviral response in people experiencing perceived social isolation (loneliness), we conducted integrative analyses of leukocyte gene regulation in humans and rhesus macaques. Five longitudinal leukocyte transcriptome surveys in 141 older adults showed up-regulation of the sympathetic nervous system (SNS), monocyte population expansion, and up-regulation of the leukocyte conserved transcriptional response to adversity (CTRA). Mechanistic analyses in a macaque model of perceived social isolation confirmed CTRA activation and identified selective up-regulation of the CD14++/CD16− classical monocyte transcriptome, functional glucocorticoid desensitization, down-regulation of Type I and II interferons, and impaired response to infection by simian immunodeficiency virus (SIV). These analyses identify neuroendocrine-related alterations in myeloid cell population dynamics as a key mediator of CTRA transcriptome skewing, which may both propagate perceived social isolation and contribute to its associated health risks. PMID:26598672

Synthesis, growth, structural, thermal and optical studies of pyrrolidinium-2-carboxylate-4-nitrophenol single crystals.

PubMed

Swarna Sowmya, N; Sampathkrishnan, S; Vidyalakshmi, Y; Sudhahar, S; Mohan Kumar, R

2015-06-15

Organic nonlinear optical material, pyrrolidinium-2-carboxylate-4-nitrophenol (PCN) was synthesized and single crystals were grown by slow evaporation solution growth method. Single crystal X-ray diffraction analysis confirmed the structure and lattice parameters of PCN crystals. Infrared, Raman and NMR spectral analyses were used to elucidate the functional groups present in the compound. The thermal behavior of synthesized compound was studied by thermogravimetric and differential scanning calorimetry (TG-DSC) analyses. The photoluminescence property was studied by exciting the crystal at 360 nm. The relative second harmonic generation (SHG) efficiency of grown crystal was estimated by using Nd:YAG laser with fundamental wavelength of 1,064 nm. Copyright © 2015 Elsevier B.V. All rights reserved.

Rare copy number variants in patients with congenital conotruncal heart defects.

PubMed

Xie, Hongbo M; Werner, Petra; Stambolian, Dwight; Bailey-Wilson, Joan E; Hakonarson, Hakon; White, Peter S; Taylor, Deanne M; Goldmuntz, Elizabeth

2017-03-01

Previous studies using different cardiac phenotypes, technologies and designs suggest a burden of large, rare or de novo copy number variants (CNVs) in subjects with congenital heart defects. We sought to identify disease-related CNVs, candidate genes, and functional pathways in a large number of cases with conotruncal and related defects that carried no known genetic syndrome. Cases and control samples were divided into two cohorts and genotyped to assess each subject's CNV content. Analyses were performed to ascertain differences in overall CNV prevalence and to identify enrichment of specific genes and functional pathways in conotruncal cases relative to healthy controls. Only findings present in both cohorts are presented. From 973 total conotruncal cases, a burden of rare CNVs was detected in both cohorts. Candidate genes from rare CNVs found in both cohorts were identified based on their association with cardiac development or disease, and/or their reported disruption in published studies. Functional and pathway analyses revealed significant enrichment of terms involved in either heart or early embryonic development. Our study tested one of the largest cohorts specifically with cardiac conotruncal and related defects. These results confirm and extend previous findings that CNVs contribute to disease risk for congenital heart defects in general and conotruncal defects in particular. As disease heterogeneity renders identification of single recurrent genes or loci difficult, functional pathway and gene regulation network analyses appear to be more informative. Birth Defects Research 109:271-295, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage

PubMed Central

2013-01-01

Background We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species' physiological capacities to withstand extreme anoxia and tissue freezing. Results Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented. Conclusions Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders. PMID:23537068

Validation of the Comprehensive ICF Core Set for obstructive pulmonary diseases from the patient's perspective.

PubMed

Marques, Alda; Jácome, Cristina; Gonçalves, Ana; Silva, Sara; Lucas, Carla; Cruz, Joana; Gabriel, Raquel

2014-06-01

This study aimed to validate the Comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for obstructive pulmonary diseases (OPDs) from the perspective of patients with chronic obstructive pulmonary disease. A cross-sectional qualitative study was carried out with outpatients with chronic obstructive pulmonary disease using focus groups with an ICF-based approach. Qualitative data were analysed using the meaning condensation procedure by two researchers with expertise in the ICF. Thirty-two participants (37.5% women; 63.8 ± 11.3 years old) were included in six focus groups. A total of 61 (86%) ICF categories of the Comprehensive ICF Core Set for OPD were confirmed. Thirty-nine additional second-level categories not included in the Core Set were identified: 15 from the body functions component, four from the body structures, nine from the activities and participation and 11 from the environmental factors. The majority of the categories included in the Comprehensive ICF Core Set for OPD were confirmed from the patients' perspective. However, additional categories, not included in the Core Set, were also reported. The categories included in the Core Set were not confirmed and the additional categories need to be investigated further to develop an instrument tailored to patients' needs. This will promote patient-centred assessments and rehabilitation interventions.

Growth, optical, ICP and thermal studies of nonlinear optical single crystal: Sodium acid phthalate (NaAP)

NASA Astrophysics Data System (ADS)

Mahadevan, M.; Arivanandhan, M.; Elangovan, K.; Anandan, P.; Ramachandran, K.

2017-07-01

Good quality single crystals of sodium acid phthalate (NaAP) were grown by slow evaporation technique. Single crystal X-ray diffraction study of the grown crystal reveals that the crystal belongs to orthorhombic system with space group B2ab. Fourier transform infrared spectrum confirms the presence of the functional groups of the grown material. Inductively coupled plasma emission spectroscopy analysis is used to confirm the presence of Na element in the sample. Thermal analysis of the NaAP crystal shows that the crystal is stable up to 140°C. Optical transmittance of the grown crystal was recorded in the wavelength range from 200 and 800 nm using UV-Vis-NIR spectrophotometer. The second harmonic generation of NaAP was analysed using Kurtz powder technique.

Influence of neural monitoring during thyroid surgery on nerve integrity and postoperative vocal function.

PubMed

Engelsman, A F; Warhurst, S; Fraser, S; Novakovic, D; Sidhu, S B

2018-06-01

Integrity of the recurrent laryngeal nerve (RLN) and the external branch of the superior laryngeal nerve (EBSLN) can be checked by intraoperative nerve monitoring (IONM) after visualization. The aim of this study was to determine the prevalence and nature of voice dysfunction following thyroid surgery with routine IONM. Thyroidectomies were performed with routine division of strap muscles and nerve monitoring to confirm integrity of the RLN and EBSLN following dissection. Patients were assessed for vocal function before surgery and at 1 and 3 months after operation. Assessment included use of the Voice Handicap Index (VHI) 10, maximum phonation time, fundamental frequency, pitch range, harmonic to noise ratio, cepstral peak prominence and smoothed cepstral peak prominence. A total of 172 nerves at risk were analysed in 102 consecutive patients undergoing elective thyroid surgery. In 23·3 per cent of EBSLNs and 0·6 per cent of RLNs nerve identification required the assistance of IONM in addition to visualization. Nerve integrity was confirmed during surgery for 98·8 per cent of EBSLNs and 98·3 per cent of RLNs. There were no differences between preoperative and postoperative VHI-10 scores. Acoustic voice assessment showed small changes in maximum phonation time at 1 and 3 months after surgery. Where there is routine division of strap muscles, thyroidectomy using nerve monitoring confirmation of RLN and EBSLN function following dissection results in no clinically significant voice change.

Bis (3-methoxy-4-hydroxybenzaldehyde-2,4,6-trinitrophenol) organic cocrystal: Synthesis and physico-chemical properties

NASA Astrophysics Data System (ADS)

Sudharsana, N.; Krishnakumar, V.; Nagalakshmi, R.

2016-10-01

A 3-methoxy-4-hydroxybenzaldehyde-2,4,6-trinitrophenol (mhba-tnp) cocrystal was grown by the slow evaporation solution growth technique using ethanol as a solvent. As-grown crystals were characterized by single crystal X-ray diffraction (XRD) study and crystallized with a centrosymmetric space group. Optical properties of the grown crystal have been studied by Ultraviolet-Visible (UV-Vis) absorption spectra in the range from 200 to 800nm and the band gap energy of the crystal was obtained as 2.8eV. Fourier transform infrared (FTIR) and micro Raman spectral analyses have been carried out to confirm the functional groups present in the title compound. Differential scanning calorimetry (DSC) and polarized light thermomicroscopy (PLTM) analyses were carried out to find the melting point. In addition, the optimized geometric parameters and the molecular orbitals were calculated using density functional theory (DFT) with the help of the Gaussian 03W software.

Evaluation of Thermal Protection Tile Transmissibility for Ground Vibration Test

NASA Technical Reports Server (NTRS)

Chung, Y. T.; Fowler, Samuel B.; Lo, Wenso; Towner, Robert

2005-01-01

Transmissibility analyses and tests were conducted on a composite panel with thermal protection system foams to evaluate the quality of the measured frequency response functions. Both the analysis and the test results indicate that the vehicle dynamic responses are fully transmitted to the accelerometers mounted on the thermal protection system in the normal direction below a certain frequency. In addition, the in-plane motions of the accelerometer mounted on the top surface of the thermal protection system behave more actively than those on the composite panel due to the geometric offset of the accelerometer from the panel in the test set-up. The transmissibility tests and analyses show that the frequency response functions measured from the accelerometers mounted on the TPS will provide accurate vehicle responses below 120 Hz for frequency and mode shape identification. By confirming that accurate dynamic responses below a given frequency can be obtained, this study increases the confidence needed for conducting the modal testing, model correlation, and model updating for a vehicle installed with TPS. '

Chemically grafted carbon-coated LiFePO4 using diazonium chemistry

NASA Astrophysics Data System (ADS)

Delaporte, Nicolas; Perea, Alexis; Amin, Ruhul; Zaghib, Karim; Bélanger, Daniel

2015-04-01

The effect of surface functionalization of aminophenyl and bromophenyl groups on carbon-coated LiFePO4 and the electrochemical properties of composite electrode containing these materials are reported. The functionalization was performed by spontaneous reduction of the corresponding in situ generated diazonium ions. The resulting chemically grafted LiFePO4/C materials were characterized by energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) to confirm the presence of the surface organic species. XRD analyses indicated the cathode material was partially oxidized. Thermogravimetric and elemental analyses revealed the loading of grafted molecules was between 0.2 and 1.1 wt.% depending on the reaction conditions. Interestingly, the electrochemical performances of the modified LiFePO4/C are not adversely affected by the presence of either aminophenyl and bromophenyl groups at the carbon surface, and in fact the grafted LiFePO4/C displayed slightly superior discharge capacity at the highest C rate investigated for a low loading of organic molecules.

New genes often acquire male-specific functions but rarely become essential in Drosophila.

PubMed

Kondo, Shu; Vedanayagam, Jeffrey; Mohammed, Jaaved; Eizadshenass, Sogol; Kan, Lijuan; Pang, Nan; Aradhya, Rajaguru; Siepel, Adam; Steinhauer, Josefa; Lai, Eric C

2017-09-15

Relatively little is known about the in vivo functions of newly emerging genes, especially in metazoans. Although prior RNAi studies reported prevalent lethality among young gene knockdowns, our phylogenomic analyses reveal that young Drosophila genes are frequently restricted to the nonessential male reproductive system. We performed large-scale CRISPR/Cas9 mutagenesis of "conserved, essential" and "young, RNAi-lethal" genes and broadly confirmed the lethality of the former but the viability of the latter. Nevertheless, certain young gene mutants exhibit defective spermatogenesis and/or male sterility. Moreover, we detected widespread signatures of positive selection on young male-biased genes. Thus, young genes have a preferential impact on male reproductive system function. © 2017 Kondo et al.; Published by Cold Spring Harbor Laboratory Press.

No mediating effects of glycemic control and inflammation on the association between vitamin D and lung function in the general population.

PubMed

Kaul, Anne; Gläser, Sven; Hannemann, Anke; Stubbe, Beate; Felix, Stefan B; Nauck, Matthias; Ewert, Ralf; Friedrich, Nele

2017-04-01

Vitamin D deficiency is discussed to be associated with lung health. While former studies focused on subjects suffering from pulmonary diseases, we aimed to investigate the association of 25-hydroxy vitamin D [25(OH)D] with lung function in the general population and examined whether mediating effects of inflammation, glycemic control or renal function exist. 1404 participants from the Study of Health in Pomerania with pulmonary function testing assessed by expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), total lung capacity and Krogh index were used. Adjusted analysis of variance, linear regression models and mediation analyses were performed. Significant positive associations between 25(OH)D levels and FEV 1 , FVC and Krogh index were found. Mediator analyses revealed no mediating effect of inflammation (fibrinogen), glycemic control (HbA1c) or renal function (eGFR) on associations with FEV 1 or FVC. With respect to Krogh-Index, the association to 25(OH)D was slightly mediated by fibrinogen with a proportion mediated of 9.7%. Significant positive associations of 25(OH)D with lung function were revealed in a general population. The proposed mediating effects of inflammation, glycemic control and renal function on these relations were not confirmed. Further studies examining the causality of the association between 25(OH)D and lung function are necessary. Copyright © 2017 Elsevier Ltd. All rights reserved.

Development of the performance confirmation program at YUCCA mountain, nevada

USGS Publications Warehouse

LeCain, G.D.; Barr, D.; Weaver, D.; Snell, R.; Goodin, S.W.; Hansen, F.D.

2006-01-01

The Yucca Mountain Performance Confirmation program consists of tests, monitoring activities, experiments, and analyses to evaluate the adequacy of assumptions, data, and analyses that form the basis of the conceptual and numerical models of flow and transport associated with a proposed radioactive waste repository at Yucca Mountain, Nevada. The Performance Confirmation program uses an eight-stage risk-informed, performance-based approach. Selection of the Performance Confirmation activities for inclusion in the Performance Confirmation program was done using a risk-informed performance-based decision analysis. The result of this analysis was a Performance Confirmation base portfolio that consists of 20 activities. The 20 Performance Confirmation activities include geologic, hydrologie, and construction/engineering testing. Some of the activities began during site characterization, and others will begin during construction, or post emplacement, and continue until repository closure.

Functional Inactivation of the Genome-Wide Association Study Obesity Gene Neuronal Growth Regulator 1 in Mice Causes a Body Mass Phenotype

PubMed Central

Lee, Angela W. S.; Berriel-Diaz, Mauricio; Loreth, Desirée; Kirsch, Matthias; Kretz, Oliver; Haas, Carola A.; de Angelis, Martin Hrabě; Herzig, Stephan; Brümmendorf, Thomas; Klingenspor, Martin; Rathjen, Fritz G.; Rozman, Jan; Nicholson, George; Cox, Roger D.; Schäfer, Michael K. E.

2012-01-01

To date, genome-wide association studies (GWAS) have identified at least 32 novel loci for obesity and body mass-related traits. However, the causal genetic variant and molecular mechanisms of specific susceptibility genes in relation to obesity are yet to be fully confirmed and characterised. Here, we examined whether the candidate gene NEGR1 encoding the neuronal growth regulator 1, also termed neurotractin or Kilon, accounts for the obesity association. To characterise the function of NEGR1 for body weight control in vivo, we generated two novel mutant mouse lines, including a constitutive NEGR1-deficient mouse line as well as an ENU-mutagenised line carrying a loss-of-function mutation (Negr1-I87N) and performed metabolic phenotypic analyses. Ablation of NEGR1 results in a small but steady reduction of body mass in both mutant lines, accompanied with a small reduction in body length in the Negr1-I87N mutants. Magnetic resonance scanning reveals that the reduction of body mass in Negr1-I87N mice is due to a reduced proportion of lean mass. Negr1-I87N mutants display reduced food intake and physical activity while normalised energy expenditure remains unchanged. Expression analyses confirmed the brain-specific distribution of NEGR1 including strong expression in the hypothalamus. In vitro assays show that NEGR1 promotes cell-cell adhesion and neurite growth of hypothalamic neurons. Our results indicate a role of NEGR1 in the control of body weight and food intake. This study provides evidence that supports the link of the GWAS candidate gene NEGR1 with body weight control. PMID:22844493

Splicing analysis for exonic and intronic mismatch repair gene variants associated with Lynch syndrome confirms high concordance between minigene assays and patient RNA analyses

PubMed Central

van der Klift, Heleen M; Jansen, Anne M L; van der Steenstraten, Niki; Bik, Elsa C; Tops, Carli M J; Devilee, Peter; Wijnen, Juul T

2015-01-01

A subset of DNA variants causes genetic disease through aberrant splicing. Experimental splicing assays, either RT-PCR analyses of patient RNA or functional splicing reporter minigene assays, are required to evaluate the molecular nature of the splice defect. Here, we present minigene assays performed for 17 variants in the consensus splice site regions, 14 exonic variants outside these regions, and two deep intronic variants, all in the DNA mismatch-repair (MMR) genes MLH1, MSH2, MSH6, and PMS2, associated with Lynch syndrome. We also included two deep intronic variants in APC and PKD2. For one variant (MLH1 c.122A>G), our minigene assay and patient RNA analysis could not confirm the previously reported aberrant splicing. The aim of our study was to further investigate the concordance between minigene splicing assays and patient RNA analyses. For 30 variants results from patient RNA analyses were available, either performed by our laboratory or presented in literature. Some variants were deliberately included in this study because they resulted in multiple aberrant transcripts in patient RNA analysis, or caused a splice effect other than the prevalent exon skip. While both methods were completely concordant in the assessment of splice effects, four variants exhibited major differences in aberrant splice patterns. Based on the present and earlier studies, together showing an almost 100% concordance of minigene assays with patient RNA analyses, we discuss the weight given to minigene splicing assays in the current criteria proposed by InSiGHT for clinical classification of MMR variants. PMID:26247049

Risk of type 1 diabetes progression in islet autoantibody-positive children can be further stratified using expression patterns of multiple genes implicated in peripheral blood lymphocyte activation and function.

PubMed

Jin, Yulan; Sharma, Ashok; Bai, Shan; Davis, Colleen; Liu, Haitao; Hopkins, Diane; Barriga, Kathy; Rewers, Marian; She, Jin-Xiong

2014-07-01

There is tremendous scientific and clinical value to further improving the predictive power of autoantibodies because autoantibody-positive (AbP) children have heterogeneous rates of progression to clinical diabetes. This study explored the potential of gene expression profiles as biomarkers for risk stratification among 104 AbP subjects from the Diabetes Autoimmunity Study in the Young (DAISY) using a discovery data set based on microarray and a validation data set based on real-time RT-PCR. The microarray data identified 454 candidate genes with expression levels associated with various type 1 diabetes (T1D) progression rates. RT-PCR analyses of the top-27 candidate genes confirmed 5 genes (BACH2, IGLL3, EIF3A, CDC20, and TXNDC5) associated with differential progression and implicated in lymphocyte activation and function. Multivariate analyses of these five genes in the discovery and validation data sets identified and confirmed four multigene models (BI, ICE, BICE, and BITE, with each letter representing a gene) that consistently stratify high- and low-risk subsets of AbP subjects with hazard ratios >6 (P < 0.01). The results suggest that these genes may be involved in T1D pathogenesis and potentially serve as excellent gene expression biomarkers to predict the risk of progression to clinical diabetes for AbP subjects. © 2014 by the American Diabetes Association.

Implementation of an integrated op-amp based chaotic neuron model and observation of its chaotic dynamics

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

Jung, Jinwoo; Lee, Jewon; Song, Hanjung

2011-03-15

This paper presents a fully integrated circuit implementation of an operational amplifier (op-amp) based chaotic neuron model with a bipolar output function, experimental measurements, and analyses of its chaotic behavior. The proposed chaotic neuron model integrated circuit consists of several op-amps, sample and hold circuits, a nonlinear function block for chaotic signal generation, a clock generator, a nonlinear output function, etc. Based on the HSPICE (circuit program) simulation results, approximated empirical equations for analyses were formulated. Then, the chaotic dynamical responses such as bifurcation diagrams, time series, and Lyapunov exponent were calculated using these empirical equations. In addition, we performedmore » simulations about two chaotic neuron systems with four synapses to confirm neural network connections and got normal behavior of the chaotic neuron such as internal state bifurcation diagram according to the synaptic weight variation. The proposed circuit was fabricated using a 0.8-{mu}m single poly complementary metal-oxide semiconductor technology. Measurements of the fabricated single chaotic neuron with {+-}2.5 V power supplies and a 10 kHz sampling clock frequency were carried out and compared with the simulated results.« less

Molecular and functional characterization of the first tick CAP2b (periviscerokinin) receptor from Rhipicephalus (Boophilus) microplus (Acari: Ixodidae).

PubMed

Yang, Yunlong; Bajracharya, Prati; Castillo, Paula; Nachman, Ronald J; Pietrantonio, Patricia V

2013-12-01

The cDNA of the receptor for CAP(2b)/periviscerokinin (PVK) neuropeptides, designated Rhimi-CAP(2b)-R, was cloned from synganglia of tick Rhipicephalus (Boophilus) microplus. This receptor is the ortholog of the insect CAP(2b)/PVK receptor, as concluded from analyses of the predicted protein sequence, phylogenetics and functional expression. Expression analyses of synganglion, salivary gland, Malpighian tubule, and ovary revealed Rhimi-CAP(2b)-R transcripts. The expression in mammalian cells of the open reading frame of Rhimi-CAP(2b)-R cDNA fused with a hemagglutinin tag at the receptor N-terminus was confirmed by immunocytochemistry. In a calcium bioluminescence assay the recombinant receptor was activated by the tick Ixodes scapularis CAP(2b)/PVK and a PVK analog with EC₅₀s of 64 nM and 249 nM, respectively. Tick pyrokinins were not active. This is the first report on the functional characterization of the CAP(2b)/PVK receptor from any tick species which will now permit the discovery of the physiological roles of these neuropeptides in ticks, as neurohormones, neuromodulators and/or neurotransmitters. Copyright © 2013 Elsevier Inc. All rights reserved.

Factor structure and gender stability in the multidimensional condom attitudes scale.

PubMed

Starosta, Amy J; Berghoff, Christopher R; Earleywine, Mitch

2015-06-01

Sexually transmitted infections continue to trouble the United States and can be attenuated through increased condom use. Attitudes about condoms are an important multidimensional factor that can affect sexual health choices and have been successfully measured using the Multidimensional Condom Attitudes Scale (MCAS). Such attitudes have the potential to vary between men and women, yet little work has been undertaken to identify if the MCAS accurately captures attitudes without being influenced by underlying gender biases. We examined the factor structure and gender invariance on the MCAS using confirmatory factor analysis and item response theory, within-subscale differential item functioning analyses. More than 770 participants provided data via the Internet. Results of differential item functioning analyses identified three items as differentially functioning between the genders, and removal of these items is recommended. Findings confirmed the previously hypothesized multidimensional nature of condom attitudes and the five-factor structure of the MCAS even after the removal of the three problematic items. In general, comparisons across genders using the MCAS seem reasonable from a methodological standpoint. Results are discussed in terms of improving sexual health research and interventions. © The Author(s) 2014.

The Extended Language Network: A Meta-Analysis of Neuroimaging Studies on Text Comprehension

PubMed Central

Ferstl, Evelyn C.; Neumann, Jane; Bogler, Carsten; von Cramon, D. Yves

2010-01-01

Language processing in context requires more than merely comprehending words and sentences. Important subprocesses are inferences for bridging successive utterances, the use of background knowledge and discourse context, and pragmatic interpretations. The functional neuroanatomy of these text comprehension processes has only recently been investigated. Although there is evidence for right-hemisphere contributions, reviews have implicated the left lateral prefrontal cortex, left temporal regions beyond Wernicke’s area, and the left dorso-medial prefrontal cortex (dmPFC) for text comprehension. To objectively confirm this extended language network and to evaluate the respective contribution of right hemisphere regions, meta-analyses of 23 neuroimaging studies are reported here. The analyses used replicator dynamics based on activation likelihood estimates. Independent of the baseline, the anterior temporal lobes (aTL) were active bilaterally. In addition, processing of coherent compared with incoherent text engaged the dmPFC and the posterior cingulate cortex. Right hemisphere activations were seen most notably in the analysis of contrasts testing specific subprocesses, such as metaphor comprehension. These results suggest task dependent contributions for the lateral PFC and the right hemisphere. Most importantly, they confirm the role of the aTL and the fronto-medial cortex for language processing in context. PMID:17557297

The Impact of Tic Severity, Comorbidity and Peer Attachment on Quality of Life Outcomes and Functioning in Tourette's Syndrome: Parental Perspectives.

PubMed

O'Hare, Deirdre; Helmes, Edward; Eapen, Valsamma; Grove, Rachel; McBain, Kerry; Reece, John

2016-08-01

The aim of this controlled, community-based study based on data from parents of youth (aged 7-16 years) with Tourette's syndrome (TS; n = 86) and parents of age and gender matched peers (n = 108) was to test several hypotheses involving a range of variables salient to the TS population, including peer attachment, quality of life, severity of tics, comorbidity, and psychological, behavioural and social dysfunction. Multivariate between-group analyses confirmed that TS group youth experienced lower quality of life, increased emotional, behavioural and social difficulties, and elevated rates of insecure peer attachment relative to controls, as reported by their primary caregiver. Results also confirmed the main hypothesis that security of peer attachment would be associated with individual variability in outcomes for youth with TS. As predicted, multivariate within-TS group analyses determined strong relationships among adverse quality of life outcomes and insecure attachment to peers, increased tic severity, and the presence of comorbid disorder. Findings suggest that youth with TS are at increased risk for insecure peer attachment and that this might be an important variable impacting the quality of life outcomes for those diagnosed.

Searching for intermediate-mass black holes via optical variability

NASA Astrophysics Data System (ADS)

Adler-Levine, Ryan; Moran, Edward C.; Kay, Laura

2018-01-01

A handful of nearby dwarf galaxies with intermediate-mass black holes (IMBHs) in their nuclei display significant optical variability on short timescales. To investigate whether dwarf galaxy AGNs as a class exhibit similar variability, we have monitored a sample of low-mass galaxies that possess spectroscopically confirmed type 1 AGNs. However, because of the variations in seeing, focus, and guiding errors that occur in images taken at different epochs, analyses based on aperture photometry are ineffective. We have thus developed a new method for matching point-spread functions in images that permits use of image subtraction photometry techniques. Applying this method to our photometric data, we have confirmed that several galaxies with IMBHs are indeed variable, which suggests that variability can be used to search for IMBHs in low-mass galaxies whose emission-line properties are ambiguous.

Growth and characterization of organic material 4-dimethylaminobenzaldehyde single crystal.

PubMed

Jebin, R P; Suthan, T; Rajesh, N P; Vinitha, G; Madhusoodhanan, U

2015-01-25

The organic material 4-dimethylaminobenzaldehyde single crystals were grown by slow evaporation technique. The grown crystal was confirmed by the single crystal and powder X-ray diffraction analyses. The functional groups of the crystal have been identified from the Fourier Transform Infrared (FTIR) and FT-Raman studies. The optical property of the grown crystal was analyzed by UV-Vis-NIR and photoluminescence (PL) spectral measurements. The thermal behavior of the grown crystal was analyzed by thermogravimetric (TG) and differential thermal analyses (DTA). Dielectric measurements were carried out with different frequencies by using parallel plate capacitor method. The third order nonlinear optical properties of 4-dimethylaminobenzaldehyde was measured by the Z-scan technique using 532 nm diode pumped continuous wave (CW) Nd:YAG laser. Copyright © 2014 Elsevier B.V. All rights reserved.

Growth and studies of cyclohexylammonium 4-methoxy benzoate single crystal for nonlinear optical applications

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

Sathya, P.; Gopalakrishnan, R., E-mail: krgkrishnan@annauniv.edu

2015-06-24

Cyclohexylammonium 4-Methoxy Benzoate (C4MB) was synthesised and the functional groups were confirmed by FTIR analysis. The purified C4MB (by repeated recrystallisation) was used for single crystal growth. Single crystal of cyclohexylammonium 4-methoxy benzoate was successfully grown by slow evaporation solution growth method at ambient temperature. Structural orientations were determined from single crystal X-ray diffractometer. Optical absorption and cut off wavelength were identified by UV-Visible spectroscopy. Thermal stability of the crystal was studied from thermogravimetric and differential thermal analyses curves. Mechanical stability of the grown crystal was analysed by Vicker’s microhardness tester. The Second Harmonic Generation (SHG) study revealed that themore » C4MB compound exhibits the SHG efficiency 3.3 times greater than KDP crystal.« less

Testosterone and sexual function in men.

PubMed

Rastrelli, Giulia; Corona, Giovanni; Maggi, Mario

2018-06-01

Testosterone (T) is deeply involved in every step of the male sexual response. However, the occurrence of sexual disorders cannot be automatically related to a decline in T levels. In fact, this relationship is complicated by organic, relational and psychological factors, which can independently impair sexual function. For example, it is recognized that erectile dysfunction (ED) can result from vascular damage as well as from low levels of T. T therapy (TTh) can improve sexual function but meta-analyses show that it improves erectile function only in men with ED and overt hypogonadism. Similarly, impaired sexual desire can result from a wide range of organic, relational and psychological factors, although it is recognized as one of the most specific symptoms of hypogonadism. Accordingly, low desire is improved by TTh in men with overt hypogonadism. The association between low T levels and delayed ejaculation has not been well studied and needs further confirmation, as does the role of TTh in such cases. Meta-analyses have found that TTh can improve orgasmic function in hypogonadal men. Clinicians should bear in mind that sexual dysfunctions have multifactorial causes and hypogonadism represents only one of these. Only hypogonadal men are likely to improve their sexual symptoms when treated with TTh. The assessment of serum T levels is mandatory before patients are prescribed TTh, as are the assessment and possible treatment of other concomitant conditions. Copyright © 2018. Published by Elsevier B.V.

Dielectric, electric and thermal properties of carboxylic functionalized multiwalled carbon nanotubes impregnated polydimethylsiloxane nanocomposite

NASA Astrophysics Data System (ADS)

Sagar, Sadia; Iqbal, Nadeem; Maqsood, Asghari

2013-06-01

The dielectric, electric and thermal properties of carboxylic functionalized multiwalled carbon nanotubes (F-MWCNT) incorporated into the polydimethylsiloxane (PDMS) were evaluated to determine their potential in the field of electronic materials. Carboxylic functionalization of the pristine multi walled carbon tubes (Ps-MWCNT) was confirmed through Fourier transform infrared spectroscopy, X-ray diffraction patterns for both Ps-MWCNTs and F-MWCNTs elaborated that crystalline behavior did not change with carboxylic moieties. Thermogravimetric and differential thermal analyses were performed to elucidate the thermal stability with increasing weight % addition of F-MWCNTs in the polymer matrix. Crystallization/glass transition / melting temperatures were evaluated using differential scanning calorimeter and it was observed that glass transition and crystallization temperatures were diminished while temperatures of first and second melting transitions were progressed with increasing F-MWCNT concentration in the PDMS matrix. Scanning electron microscopy and energy dispersive x-ray spectroscopy were carried out to confirm the morphology, functionalization, and uniform dispersion of F-MWCNTs in the polymer matrix. Electrical resistivity at temperature range (100-300°C), dielectric loss (tanδ) and dielectric parameters (epsilon/ epsilon//) were measured in the frequency range (1MHz-3GHz). The measured data simulate that the aforementioned properties were influenced by increasing filler contents in the polymer matrix because of the high polarization of conductive F-MWCNTs at the reinforcement/polymer interface.

Evaluation of mechanical and transport properties of Zr2CoSi Heusler alloy

NASA Astrophysics Data System (ADS)

Yousuf, Saleem; Khandy, S. A.; Bhat, T. M.; Gupta, D. C.

2017-05-01

Systematic investigation of mechanical and transport properties of Zr2CoSi within the density functional theory have been analysed. From the elastic constants, the shear modulus, Young's modulus, Poisson's ratio, we conclude the ductile nature of alloy. Thermoelectric properties show that Zr2CoSi as an n-type thermoelectric material with a higher increase in Seebeck coefficient with temperature. Further the power factor analysis confirms the heavily doping of the alloy fruitful for increase in thermoelectric performance and its use for the future thermoelectric spin generators.

Segregation of face sensitive areas within the fusiform gyrus using global signal regression? A study on amygdala resting-state functional connectivity.

PubMed

Kruschwitz, Johann D; Meyer-Lindenberg, Andreas; Veer, Ilya M; Wackerhagen, Carolin; Erk, Susanne; Mohnke, Sebastian; Pöhland, Lydia; Haddad, Leila; Grimm, Oliver; Tost, Heike; Romanczuk-Seiferth, Nina; Heinz, Andreas; Walter, Martin; Walter, Henrik

2015-10-01

The application of global signal regression (GSR) to resting-state functional magnetic resonance imaging data and its usefulness is a widely discussed topic. In this article, we report an observation of segregated distribution of amygdala resting-state functional connectivity (rs-FC) within the fusiform gyrus (FFG) as an effect of GSR in a multi-center-sample of 276 healthy subjects. Specifically, we observed that amygdala rs-FC was distributed within the FFG as distinct anterior versus posterior clusters delineated by positive versus negative rs-FC polarity when GSR was performed. To characterize this effect in more detail, post hoc analyses revealed the following: first, direct overlays of task-functional magnetic resonance imaging derived face sensitive areas and clusters of positive versus negative amygdala rs-FC showed that the positive amygdala rs-FC cluster corresponded best with the fusiform face area, whereas the occipital face area corresponded to the negative amygdala rs-FC cluster. Second, as expected from a hierarchical face perception model, these amygdala rs-FC defined clusters showed differential rs-FC with other regions of the visual stream. Third, dynamic connectivity analyses revealed that these amygdala rs-FC defined clusters also differed in their rs-FC variance across time to the amygdala. Furthermore, subsample analyses of three independent research sites confirmed reliability of the effect of GSR, as revealed by similar patterns of distinct amygdala rs-FC polarity within the FFG. In this article, we discuss the potential of GSR to segregate face sensitive areas within the FFG and furthermore discuss how our results may relate to the functional organization of the face-perception circuit. © 2015 Wiley Periodicals, Inc.

Brief Report: Late-Onset Cryopyrin-Associated Periodic Syndrome Due to Myeloid-Restricted Somatic NLRP3 Mosaicism.

PubMed

Mensa-Vilaro, Anna; Teresa Bosque, María; Magri, Giuliana; Honda, Yoshitaka; Martínez-Banaclocha, Helios; Casorran-Berges, Marta; Sintes, Jordi; González-Roca, Eva; Ruiz-Ortiz, Estibaliz; Heike, Toshio; Martínez-Garcia, Juan J; Baroja-Mazo, Alberto; Cerutti, Andrea; Nishikomori, Ryuta; Yagüe, Jordi; Pelegrín, Pablo; Delgado-Beltran, Concha; Aróstegui, Juan I

2016-12-01

Gain-of-function NLRP3 mutations cause cryopyrin-associated periodic syndrome (CAPS), with gene mosaicism playing a relevant role in the pathogenesis. This study was undertaken to characterize the genetic cause underlying late-onset but otherwise typical CAPS. We studied a 64-year-old patient who presented with recurrent episodes of urticaria-like rash, fever, conjunctivitis, and oligoarthritis at age 56 years. DNA was extracted from both unfractionated blood and isolated leukocyte and CD34+ subpopulations. Genetic studies were performed using both the Sanger method of DNA sequencing and next-generation sequencing (NGS) methods. In vitro and ex vivo analyses were performed to determine the consequences that the presence of the variant have in the normal structure or function of the protein of the detected variant. NGS analyses revealed the novel p.Gln636Glu NLRP3 variant in unfractionated blood, with an allele frequency (18.4%) compatible with gene mosaicism. Sanger sequence chromatograms revealed a small peak corresponding to the variant allele. Amplicon-based deep sequencing revealed somatic NLRP3 mosaicism restricted to myeloid cells (31.8% in monocytes, 24.6% in neutrophils, and 11.2% in circulating CD34+ common myeloid progenitor cells) and its complete absence in lymphoid cells. Functional analyses confirmed the gain-of-function behavior of the gene variant and hyperactivity of the NLRP3 inflammasome in the patient. Treatment with anakinra resulted in good control of the disease. We identified the novel gain-of-function p.Gln636Glu NLRP3 mutation, which was detected as a somatic mutation restricted to myeloid cells, as the cause of late-onset but otherwise typical CAPS. Our results expand the diversity of CAPS toward milder phenotypes than previously reported, including those starting during adulthood. © 2016, American College of Rheumatology.

Collins azimuthal asymmetries of hadron production inside jets

DOE PAGES

Kang, Zhong -Bo; Prokudin, Alexei; Ringer, Felix; ...

2017-10-18

Here, we investigate the Collins azimuthal asymmetry of hadrons produced inside jets in transversely polarized proton-proton collisions. Recently, the quark transversity distributions and the Collins fragmentation functions have been extracted within global analyses from data of the processes semi-inclusive deep inelastic scattering and electron-positron annihilation. We calculate the Collins azimuthal asymmetry for charged pions inside jets using these extractions for RHIC kinematics at center-of-mass energies of 200 and 500 GeV. We compare our results with recent data from the STAR Collaboration at RHIC and find good agreement, which confirms the universality of the Collins fragmentation functions. In addition, we furthermore » explore the impact of transverse momentum dependent evolution effects.« less

Collins azimuthal asymmetries of hadron production inside jets

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

Kang, Zhong -Bo; Prokudin, Alexei; Ringer, Felix

Here, we investigate the Collins azimuthal asymmetry of hadrons produced inside jets in transversely polarized proton-proton collisions. Recently, the quark transversity distributions and the Collins fragmentation functions have been extracted within global analyses from data of the processes semi-inclusive deep inelastic scattering and electron-positron annihilation. We calculate the Collins azimuthal asymmetry for charged pions inside jets using these extractions for RHIC kinematics at center-of-mass energies of 200 and 500 GeV. We compare our results with recent data from the STAR Collaboration at RHIC and find good agreement, which confirms the universality of the Collins fragmentation functions. In addition, we furthermore » explore the impact of transverse momentum dependent evolution effects.« less

TSH Receptor Function Is Required for Normal Thyroid Differentiation in Zebrafish

PubMed Central

Opitz, Robert; Maquet, Emilie; Zoenen, Maxime; Dadhich, Rajesh

2011-01-01

TSH is the primary physiological regulator of thyroid gland function. The effects of TSH on thyroid cells are mediated via activation of its membrane receptor [TSH receptor (TSHR)]. In this study, we examined functional thyroid differentiation in zebrafish and characterized the role of TSHR signaling during thyroid organogenesis. Cloning of a cDNA encoding zebrafish Tshr showed conservation of primary structure and functional properties between zebrafish and mammalian TSHR. In situ hybridization confirmed that the thyroid is the major site of tshr expression during zebrafish development. In addition, we identified tpo, iyd, duox, and duoxa as novel thyroid differentiation markers in zebrafish. Temporal analyses of differentiation marker expression demonstrated the induction of an early thyroid differentiation program along with thyroid budding, followed by a delayed onset of duox and duoxa expression coincident with thyroid hormone synthesis. Furthermore, comparative analyses in mouse and zebrafish revealed for the first time a thyroid-enriched expression of cell death regulators of the B-cell lymphoma 2 family during early thyroid morphogenesis. Knockdown of tshr function by morpholino microinjection into embryos did not affect early thyroid morphogenesis but caused defects in later functional differentiation. The thyroid phenotype observed in tshr morphants at later stages comprised a reduction in number and size of functional follicles, down-regulation of differentiation markers, as well as reduced thyroid transcription factor expression. A comparison of our results with phenotypes observed in mouse models of defective TSHR and cAMP signaling highlights the value of zebrafish as a model to enhance the understanding of functional differentiation in the vertebrate thyroid. PMID:21737742

Studying self-awareness in children: validation of the Questionnaire of Executive Functioning (QEF).

PubMed

Geurten, Marie; Catale, Corinne; Geurten, Claire; Wansard, Murielle; Meulemans, Thierry

2016-05-01

People with accurate representations of their own cognitive functioning (i.e. cognitive self-awareness) tend to use appropriate strategies to regulate their behavior. Due to the lack of appropriate instruments, few studies have examined the development of this ability among children. This study tested the measurement properties of the self-rating and other-rating forms of the Questionnaire of Executive Functioning (QEF), designed to tap children's knowledge of their executive functioning. Specifically, the construct, convergent, and discriminant validities were investigated and a self-other discrepancy score was computed to assess children's executive self-awareness. Participants were 317 children aged 7-14 years old. Confirmatory factor analyses carried out on the QEF confirmed the eight-factor structure of both versions. There were significant correlations between the QEF and the parent versions of the Behavior Rating Inventory of Executive Function, the Dysexecutive Questionnaire for Children, and the Childhood Executive Functioning Inventory. Both forms of the QEF were able to distinguish between children who had sustained a traumatic brain injury (TBI) and control participants. A statistical difference was observed between the TBI and control groups on this score, suggesting that TBI may trigger self-awareness impairments in children. The good psychometric properties of the two forms of the QEF were established. Furthermore, results of the analyses carried out on the different discrepancy scores seem to indicate that the QEF could help clinicians to detect patients with self-awareness deficits.

The relative contributions of function, perceived psychological burden and partner support to cognitive distress in bladder cancer.

PubMed

Heyes, Susan M; Bond, Malcolm J; Harrington, Ann; Belan, Ingrid

2016-09-01

Bladder cancer is a genitourinary disease of increasing incidence. Despite improvements in treatment, outcomes remain equivocal with high recurrence rates. It is associated with poor psychosocial outcomes due to reduced functioning of the genitourinary system. The objective of these analyses was to query whether reported loss of function or the perception of psychological burden caused by this functional impedance was the key to understanding psychosocial outcomes. The sample comprised 119 participants with a confirmed diagnosis of bladder cancer. They completed a self-report questionnaire comprising the Bladder Cancer Index, Mini-mental Adjustment to Cancer Scale, Psychosocial Adjustment to Illness Scale and standard sociodemographic details. Simple mediation and serial mediation were used to explore the potential for psychological burden to mediate associations between loss of function and cognitive distress, and the potential additional contribution of positive partner support on these relationships. Age and duration of cancer were considered as covariates. Simple mediation demonstrated that the association between function and cognitive distress was fully mediated by perceived psychological burden. Serial mediation, which allowed for the addition of partner support, again demonstrated full mediation, with partner support being the key predictive variable. These analyses emphasise the importance of an appreciation of individuals' interpretation of the burden occasioned by bladder cancer and the role of a supportive partner. The implications for management discussions and support services in alleviating negative psychological outcomes in bladder cancer are highlighted. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function

PubMed Central

Raychaudhuri, Soumya; Korn, Joshua M.; McCarroll, Steven A.; Altshuler, David; Sklar, Pamela; Purcell, Shaun; Daly, Mark J.

2010-01-01

Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied “pathway” analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software package. PMID:20838587

Maternal Pre-Pregnancy Obesity Is Associated with Altered Placental Transcriptome.

PubMed

Altmäe, Signe; Segura, Maria Teresa; Esteban, Francisco J; Bartel, Sabine; Brandi, Pilar; Irmler, Martin; Beckers, Johannes; Demmelmair, Hans; López-Sabater, Carmen; Koletzko, Berthold; Krauss-Etschmann, Susanne; Campoy, Cristina

2017-01-01

Maternal obesity has a major impact on pregnancy outcomes. There is growing evidence that maternal obesity has a negative influence on placental development and function, thereby adversely influencing offspring programming and health outcomes. However, the molecular mechanisms underlying these processes are poorly understood. We analysed ten term placenta's whole transcriptomes in obese (n = 5) and normal weight women (n = 5), using the Affymetrix microarray platform. Analyses of expression data were carried out using non-parametric methods. Hierarchical clustering and principal component analysis showed a clear distinction in placental transcriptome between obese and normal weight women. We identified 72 differentially regulated genes, with most being down-regulated in obesity (n = 61). Functional analyses of the targets using DAVID and IPA confirm the dysregulation of previously identified processes and pathways in the placenta from obese women, including inflammation and immune responses, lipid metabolism, cancer pathways, and angiogenesis. In addition, we detected new molecular aspects of obesity-derived effects on the placenta, involving the glucocorticoid receptor signalling pathway and dysregulation of several genes including CCL2, FSTL3, IGFBP1, MMP12, PRG2, PRL, QSOX1, SERPINE2 and TAC3. Our global gene expression profiling approach demonstrates that maternal obesity creates a unique in utero environment that impairs the placental transcriptome.

Duplicated growth hormone genes in a passerine bird, the jungle crow (Corvus macrorhynchos).

PubMed

Arai, Natsumi; Iigo, Masayuki

2010-07-02

Molecular cloning, molecular phylogeny, gene structure and expression analyses of growth hormone (GH) were performed in a passerine bird, the jungle crow (Corvus macrorhynchos). Unexpectedly, duplicated GH cDNA and genes were identified and designated as GH1A and GH1B. In silico analyses identified the zebra finch orthologs. Both GH genes encode 217 amino acid residues and consist of five exons and four introns, spanning 5.2 kbp in GH1A and 4.2 kbp in GH1B. Predicted GH proteins of the jungle crow and zebra finch contain four conserved cysteine residues, suggesting duplicated GH genes are functional. Molecular phylogenetic analysis revealed that duplication of GH genes occur after divergence of the passerine lineage from the other avian orders as has been suggested from partial genomic DNA sequences of passerine GH genes. RT-PCR analyses confirmed expression of GH1A and GH1B in the pituitary gland. In addition, GH1A gene is expressed in all the tissues examined. However, expression of GH1B is confined to several brain areas and blood cells. These results indicate that the regulatory mechanisms of duplicated GH genes are different and that duplicated GH genes exert both endocrine and autocrine/paracrine functions. Copyright 2010 Elsevier Inc. All rights reserved.

Strength and fine dexterity recovery profiles after a primary motor cortex insult and effect of a neuronal cell graft.

PubMed

Vaysse, Laurence; Conchou, Fabrice; Demain, Boris; Davoust, Carole; Plas, Benjamin; Ruggieri, Cyrielle; Benkaddour, Mehdi; Simonetta-Moreau, Marion; Loubinoux, Isabelle

2015-08-01

The aim of this study was to set up (a) a large primary motor cortex (M1) lesion in rodent and (b) the conditions for evaluating a long-lasting motor deficit in order to propose a valid model to test neuronal replacement therapies aimed at improving motor deficit recovery. A mitochondrial toxin, malonate, was injected to induce extensive destruction of the forelimb M1 cortex. Three key motor functions that are usually evaluated following cerebral lesion in the clinic-strength, target reaching, and fine dexterity-were assessed in rats by 2 tests, a forelimb grip strength test and a skilled reaching task (staircase) for reaching and dexterity. The potential enhancement of postlesion recovery induced by a neuronal cell transplantation was then explored and confirmed by histological analyses. Both tests showed a severe functional impairment 2 days post lesion, however, reaching remained intact. Deficits in forelimb strength were long lasting (up to 3 months) but spontaneously recovered despite the extensive lesion size. This natural grip strength recovery could be enhanced by cell therapy. Histological analyses confirmed the presence of grafted cells 3 months postgraft and showed partial tissue reconstruction with some living neuronal cells in the graft. In contrast, fine dexterity never recovered in the staircase test even after grafting. These results suggest that cell replacement was only partially effective and that the forelimb M1 area may be a node of the sensorimotor network, where compensation from secondary pathways could account for strength recovery but recovery of forelimb fine dexterity requires extensive tissue reconstruction. (c) 2015 APA, all rights reserved).

Avian reflex and electroencephalogram responses in different states of consciousness.

PubMed

Sandercock, Dale A; Auckburally, Adam; Flaherty, Derek; Sandilands, Victoria; McKeegan, Dorothy E F

2014-06-22

Defining states of clinical consciousness in animals is important in veterinary anaesthesia and in studies of euthanasia and welfare assessment at slaughter. The aim of this study was to validate readily observable reflex responses in relation to different conscious states, as confirmed by EEG analysis, in two species of birds under laboratory conditions (35-week-old layer hens (n=12) and 11-week-old turkeys (n=10)). We evaluated clinical reflexes and characterised electroencephalograph (EEG) activity (as a measure of brain function) using spectral analyses in four different clinical states of consciousness: conscious (fully awake), semi-conscious (sedated), unconscious-optimal (general anaesthesia), unconscious-sub optimal (deep hypnotic state), as well as assessment immediately following euthanasia. Jaw or neck muscle tone was the most reliable reflex measure distinguishing between conscious and unconscious states. Pupillary reflex was consistently observed until respiratory arrest. Nictitating membrane reflex persisted for a short time (<1 min) after respiratory arrest and brain death (isoelectric EEG). The results confirm that the nictitating membrane reflex is a conservative measure of death in poultry. Using spectral analyses of the EEG waveforms it was possible to readily distinguish between the different states of clinical consciousness. In all cases, when birds progressed from a conscious to unconscious state; total spectral power (PTOT) significantly increased, whereas median (F50) and spectral edge (F95) frequencies significantly decreased. This study demonstrates that EEG analysis can differentiate between clinical states (and loss of brain function at death) in birds and provides a unique integration of reflex responses and EEG activity. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular evolution of the betagamma lens crystallin superfamily: evidence for a retained ancestral function in gamma N crystallins?

PubMed

Weadick, Cameron J; Chang, Belinda S W

2009-05-01

Within the vertebrate eye, betagamma crystallins are extremely stable lens proteins that are uniquely adapted to increase refractory power while maintaining transparency. Unlike alpha crystallins, which are well-characterized, multifunctional proteins that have important functions both in and out of the lens, betagamma lens crystallins are a diverse group of proteins with no clear ancestral or contemporary nonlens role. We carried out phylogenetic and molecular evolutionary analyses of the betagamma-crystallin superfamily in order to study the evolutionary history of the gamma N crystallins, a recently discovered, biochemically atypical family suggested to possess a divergent or ancestral function. By including nonlens, betagamma-motif-containing sequences in our analysis as outgroups, we confirmed the phylogenetic position of the gamma N family as sister to other gamma crystallins. Using maximum likelihood codon models to estimate lineage-specific nonsynonymous-to-synonymous rate ratios revealed strong positive selection in all of the early lineages within the betagamma family, with the striking exception of the lineage leading to the gamma N crystallins which was characterized by strong purifying selection. Branch-site analysis, used to identify candidate sites involved in functional divergence between gamma N crystallins and its sister clade containing all other gamma crystallins, identified several positively selected changes at sites of known functional importance in the betagamma crystallin protein structure. Further analyses of a fish-specific gamma N crystallin gene duplication revealed a more recent episode of positive selection in only one of the two descendant lineages (gamma N2). Finally, from the guppy, Poecilia reticulata, we isolated complete gamma N1 and gamma N2 coding sequence data from cDNA and partial coding sequence data from genomic DNA in order to confirm the presence of a novel gamma N2 intron, discovered through data mining of two pufferfish genomes. We conclude that the function of the gamma N family likely resembles the ancestral vertebrate betagamma crystallin more than other betagamma families. Furthermore, owing to the presence of an additional intron in some fish gamma N2 crystallins, and the inferred action of positive selection following the fish-specific gamma N duplication, we suggest that further study of fish gamma N crystallins will be critical in further elucidating possible ancestral functions of gamma N crystallins and any nonstructural role they may have.

Increased left hemisphere impairment in high-functioning autism: a tract based spatial statistics study.

PubMed

Perkins, Thomas John; Stokes, Mark Andrew; McGillivray, Jane Anne; Mussap, Alexander Julien; Cox, Ivanna Anne; Maller, Jerome Joseph; Bittar, Richard Garth

2014-11-30

There is evidence emerging from Diffusion Tensor Imaging (DTI) research that autism spectrum disorders (ASD) are associated with greater impairment in the left hemisphere. Although this has been quantified with volumetric region of interest analyses, it has yet to be tested with white matter integrity analysis. In the present study, tract based spatial statistics was used to contrast white matter integrity of 12 participants with high-functioning autism or Aspergers syndrome (HFA/AS) with 12 typically developing individuals. Fractional Anisotropy (FA) was examined, in addition to axial, radial and mean diffusivity (AD, RD and MD). In the left hemisphere, participants with HFA/AS demonstrated significantly reduced FA in predominantly thalamic and fronto-parietal pathways and increased RD. Symmetry analyses confirmed that in the HFA/AS group, WM disturbance was significantly greater in the left compared to right hemisphere. These findings contribute to a growing body of literature suggestive of reduced FA in ASD, and provide preliminary evidence for RD impairments in the left hemisphere. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Construct validation of SF-36 Malay version among type 2 diabetes mellitus patients

NASA Astrophysics Data System (ADS)

Yap, Bee Wah; Jannoo, Zeinab; Razali, Nornadiah Mohd; Ghani, Nor Azura Md.; Lazim, Mohamad Alias

2015-02-01

The Short Form 36 (SF-36) is one of the most widely used generic health status measure. This study used the SF-36 Health Survey instrument to investigate the functional health and well-being of Malay Type 2 Diabetes Mellitus patients in Malaysia. The survey was carried out in three local hospitals in Selangor. The method of questionnaire administration was both self-administered and interviewer administered. A total of 354 questionnaires was returned, but only 295 questionnaires with no missing data were analyzed. Confirmatory Factor Analysis (CFA) was used to confirm the first-order and third-order CFA models. The higher order analyses included a third-order CFA models with two second-order factors (physical and mental component) and three second-order factors (physical, general well-being and mental health) and both showed satisfactory model fit indices. This study confirmed the multidimensional factor structure of the SF-36.

Factor structure of the Japanese Interpersonal Competence Scale.

PubMed

Matsudaira, Tomomi; Fukuhara, Taihei; Kitamura, Toshinori

2008-04-01

Assessing social competence is important for clinical and preventive interventions of depression. The aim of the present paper was to examine the factor structure of the Japanese Interpersonal Competence Scale (JICS). Exploratory and confirmatory factor analysis was performed on the survey responses of 730 participants. Simultaneous multigroup analyses were conducted to confirm factor stability across psychological health status and sex differences. Two factors, which represent Perceptive Ability and Self-Restraint, were confirmed to show a moderate correlation. Perceptive Ability involves a more cognitive aspect of social competence, while Self-Restraint involves a more behavioral aspect, both of which are considered to reflect the emotion-based relating style specific to the Japanese people: indulgent dependence (amae) and harmony (wa). In addition, Self-Restraint may be linked to social functioning. Both constructs may confound a respondent's perceived confidence. Despite its shortcomings, the JICS is a unique measure of social competence in the Japanese cultural context.

Growth of L-Valinium Aluminium Chloride single crystal for OLED and super-capacitor applications

NASA Astrophysics Data System (ADS)

Kalaivani, D.; Vijayalakshmi, S.; Theras, J. Elberin Mary; Jayaraman, D.; Joseph, V.

2015-12-01

L-Valinium Aluminium Chloride (LVAC), a novel semi-organic material, was grown using slow evaporation under isothermal condition. The single crystal data reveal that the grown crystal belongs to monoclinic system. The SEM micrographs give clear picture about the surface morphology. Further, they confirm the inclusion of aluminium chloride into atomic sites of L-Valine. The compositional elements present in the crystal were identified through EDAX analysis. The mass spectral analysis was carried out to determine the molecular weight of the grown crystal. The optical transparency of the grown crystal was investigated by UV-vis-NIR spectrum. FTIR spectral study was used to identify the functional groups present in the grown material. The luminescence characteristics of grown material were analysed to confirm the effect of metal ion on the ligand. This property makes the material suitable for OLED application. The supercapacitive performance of the grown crystal was finally studied using cyclic voltammetry.

Long-term Effects of Off-Pump Coronary Bypass Versus Conventional Coronary Bypass Grafting on Renal Function.

PubMed

Hynes, Conor F; Colo, Sanchez; Amdur, Richard L; Chawla, Lakhmir S; Greenberg, Michael D; Trachiotis, Gregory D

2016-01-01

This study aimed to evaluate the short- and long-term effects of conventional on-pump coronary bypass grafting (cCABG) compared with off-pump coronary artery bypass (OPCAB) on renal function. A retrospective review of patients undergoing coronary bypass grafting from 2004 through 2013 at a single center was conducted. Preoperative renal function, perioperative acute kidney injury, and long-term glomerular filtration were evaluated. Multivariable analyses were used to determine factors contributing to short- and long-term renal impairment. A total of 234 patients underwent cCABG, and 582 underwent OPCAB. Patients undergoing OPCAB were significantly older, had greater preoperative renal dysfunction, had greater functional dependence, and took more hypertension medications. Multivariable analyses found that 30-day acute kidney injury was an independent risk factor for a 10% decline in glomerular filtration rate at 1 and 5 years (P < 0.0001 and 0.002, respectively). However, the use of cardiopulmonary bypass was not found to influence long-term renal function (P = 0.78 at 1 year, P = 0.76 at 5 years). The percentage of patients experiencing a 10% drop in renal function from baseline at 1 year (33% OPCAB, 35% cCABG; P = 0.73) and 5 years (16% OPCAB, 16% cCABG; P = 0.93) were not significantly different. Independent predictors of acute kidney injury included baseline kidney function (P = 0.04) and age (P < 0.0001), whereas cardiopulmonary bypass did not affect the incidence (P = 0.17). A propensity-matched analysis confirmed these findings. Acute kidney injury is a risk factor for long-term renal dysfunction after either bypass method and was not greater after cCABG compared with OPCAB. Patients undergoing OPCAB did not experience greater decrease in long-term kidney function despite having worse baseline kidney function.

Protein Composition of Trypanosoma brucei Mitochondrial Membranes

PubMed Central

Acestor, Nathalie; Panigrahi, Aswini K.; Ogata, Yuko; Anupama, Atashi; Stuart, Kenneth D.

2010-01-01

Mitochondria consist of four compartments, outer membrane, intermembrane space, inner membrane and matrix; each harboring specific functions and structures. In this study, we used mass spectrometry (LC-MS/MS) to characterize the protein composition of Trypanosoma brucei mitochondrial membranes, which were enriched by different biochemical fractionation techniques. The analyses identified 202 proteins that contain one or more transmembrane domain(s) and/or positive GRAVY scores. Of these, various criteria were used to assign 72 proteins to mitochondrial membranes with high confidence, and 106 with moderate to low confidence. The sub-cellular localization of a selected subset of 13 membrane assigned proteins was confirmed by tagging and immunofluorescence analysis. While most proteins assigned to mitochondrial membrane have putative roles in metabolic, energy generating, and transport processes, ~50% have no known function. These studies result in a comprehensive profile of the composition and sub-organellar location of proteins in the T. brucei mitochondrion thus, providing useful information on mitochondrial functions. PMID:19834910

Phase dynamics of coupled oscillators reconstructed from data

NASA Astrophysics Data System (ADS)

Rosenblum, Michael; Kralemann, Bjoern; Pikovsky, Arkady

2013-03-01

We present a technique for invariant reconstruction of the phase dynamics equations for coupled oscillators from data. The invariant description is achieved by means of a transformation of phase estimates (protophases) obtained from general scalar observables to genuine phases. Staring from the bivariate data, we obtain the coupling functions in terms of these phases. We discuss the importance of the protophase-to-phase transformation for characterization of strength and directionality of interaction. To illustrate the technique we analyse the cardio-respiratory interaction on healthy humans. Our invariant approach is confirmed by high similarity of the coupling functions obtained from different observables of the cardiac system. Next, we generalize the technique to cover the case of small networks of coupled periodic units. We use the partial norms of the reconstructed coupling functions to quantify directed coupling between the oscillators. We illustrate the method by different network motifs for three coupled oscillators. We also discuss nonlinear effects in coupling.

Do attentional capacities and processing speed mediate the effect of age on executive functioning?

PubMed

Gilsoul, Jessica; Simon, Jessica; Hogge, Michaël; Collette, Fabienne

2018-02-06

The executive processes are well known to decline with age, and similar data also exists for attentional capacities and processing speed. Therefore, we investigated whether these two last nonexecutive variables would mediate the effect of age on executive functions (inhibition, shifting, updating, and dual-task coordination). We administered a large battery of executive, attentional and processing speed tasks to 104 young and 71 older people, and we performed mediation analyses with variables showing a significant age effect. All executive and processing speed measures showed age-related effects while only the visual scanning task performance (selective attention) was explained by age when controlled for gender and educational level. Regarding mediation analyses, visual scanning partially mediated the age effect on updating while processing speed partially mediated the age effect on shifting, updating and dual-task coordination. In a more exploratory way, inhibition was also found to partially mediate the effect of age on the three other executive functions. Attention did not greatly influence executive functioning in aging while, in agreement with the literature, processing speed seems to be a major mediator of the age effect on these processes. Interestingly, the global pattern of results seems also to indicate an influence of inhibition but further studies are needed to confirm the role of that variable as a mediator and its relative importance by comparison with processing speed.

Protein kinases responsible for the phosphorylation of the nuclear egress core complex of human cytomegalovirus.

PubMed

Sonntag, Eric; Milbradt, Jens; Svrlanska, Adriana; Strojan, Hanife; Häge, Sigrun; Kraut, Alexandra; Hesse, Anne-Marie; Amin, Bushra; Sonnewald, Uwe; Couté, Yohann; Marschall, Manfred

2017-10-01

Nuclear egress of herpesvirus capsids is mediated by a multi-component nuclear egress complex (NEC) assembled by a heterodimer of two essential viral core egress proteins. In the case of human cytomegalovirus (HCMV), this core NEC is defined by the interaction between the membrane-anchored pUL50 and its nuclear cofactor, pUL53. NEC protein phosphorylation is considered to be an important regulatory step, so this study focused on the respective role of viral and cellular protein kinases. Multiply phosphorylated pUL50 varieties were detected by Western blot and Phos-tag analyses as resulting from both viral and cellular kinase activities. In vitro kinase analyses demonstrated that pUL50 is a substrate of both PKCα and CDK1, while pUL53 can also be moderately phosphorylated by CDK1. The use of kinase inhibitors further illustrated the importance of distinct kinases for core NEC phosphorylation. Importantly, mass spectrometry-based proteomic analyses identified five major and nine minor sites of pUL50 phosphorylation. The functional relevance of core NEC phosphorylation was confirmed by various experimental settings, including kinase knock-down/knock-out and confocal imaging, in which it was found that (i) HCMV core NEC proteins are not phosphorylated solely by viral pUL97, but also by cellular kinases; (ii) both PKC and CDK1 phosphorylation are detectable for pUL50; (iii) no impact of PKC phosphorylation on NEC functionality has been identified so far; (iv) nonetheless, CDK1-specific phosphorylation appears to be required for functional core NEC interaction. In summary, our findings provide the first evidence that the HCMV core NEC is phosphorylated by cellular kinases, and that the complex pattern of NEC phosphorylation has functional relevance.

Risk Factors for Non-Suicidal Self-Injury Among Trans Youth.

PubMed

Arcelus, Jon; Claes, Laurence; Witcomb, Gemma L; Marshall, Ellen; Bouman, Walter Pierre

2016-03-01

Previous research has reported high levels of non-suicidal self-injury (NSSI) in trans populations and younger age has been identified as a risk factor. To explore the prevalence of NSSI in a large group of young trans people and to identify risk factors for this group. Sociodemographic variables and measurements of NSSI (Self-Injury Questionnaire), psychopathology (Symptom Checklist-90-Revised), self-esteem (Rosenberg Self-Esteem Scale), victimization (Experiences of Transphobia Scale), interpersonal functioning (Inventory of Interpersonal Problems), and social support (Multidimensional Scale of Perceived Social Support). Two hundred sixty-eight young people attending a national gender clinic completed questionnaires assessing presence and frequency of NSSI and levels of general psychopathology, depression, anxiety, interpersonal problems, self-esteem, social support, transphobia, and information on hormone treatment. A lifetime presence of NSSI was identified in 46.3% of patients and 28.73% reported currently engaging in NSSI (within at least the past few months). Analyses showed that those with a lifetime presence of NSSI had significantly greater general psychopathology, lower self-esteem, had suffered more transphobia, and experienced greater interpersonal problems than those without NSSI. Findings were similar when comparing current with non-current NSSI. Overall, natal male patients reported less social support than natal female patients, but current NSSI was more common in natal female patients. Regression analyses confirmed that natal female gender and greater general psychopathology predicted current and lifetime NSSI. Further analyses confirmed that general psychopathology itself could be predicted by transphobic experiences, low self-esteem, and interpersonal problems, but not by the use of cross-sex hormones. These findings confirm that NSSI is common in trans youth and emphasize the need for interventions that decrease transphobia, increase social support, and help trans youth navigate their relationships with others to decrease psychopathology and NSSI. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Functional Analyses of a Novel Splice Variant in the CHD7 Gene, Found by Next Generation Sequencing, Confirm Its Pathogenicity in a Spanish Patient and Diagnose Him with CHARGE Syndrome.

PubMed

Villate, Olatz; Ibarluzea, Nekane; Fraile-Bethencourt, Eugenia; Valenzuela, Alberto; Velasco, Eladio A; Grozeva, Detelina; Raymond, F L; Botella, María P; Tejada, María-Isabel

2018-01-01

Mutations in CHD7 have been shown to be a major cause of CHARGE syndrome, which presents many symptoms and features common to other syndromes making its diagnosis difficult. Next generation sequencing (NGS) of a panel of intellectual disability related genes was performed in an adult patient without molecular diagnosis. A splice donor variant in CHD7 (c.5665 + 1G > T) was identified. To study its potential pathogenicity, exons and flanking intronic sequences were amplified from patient DNA and cloned into the pSAD ® splicing vector. HeLa cells were transfected with this construct and a wild-type minigene and functional analysis were performed. The construct with the c.5665 + 1G > T variant produced an aberrant transcript with an insert of 63 nucleotides of intron 28 creating a premature termination codon (TAG) 25 nucleotides downstream. This would lead to the insertion of 8 new amino acids and therefore a truncated 1896 amino acid protein. As a result of this, the patient was diagnosed with CHARGE syndrome. Functional analyses underline their usefulness for studying the pathogenicity of variants found by NGS and therefore its application to accurately diagnose patients.

Detecting Large-Scale Brain Networks Using EEG: Impact of Electrode Density, Head Modeling and Source Localization

PubMed Central

Liu, Quanying; Ganzetti, Marco; Wenderoth, Nicole; Mantini, Dante

2018-01-01

Resting state networks (RSNs) in the human brain were recently detected using high-density electroencephalography (hdEEG). This was done by using an advanced analysis workflow to estimate neural signals in the cortex and to assess functional connectivity (FC) between distant cortical regions. FC analyses were conducted either using temporal (tICA) or spatial independent component analysis (sICA). Notably, EEG-RSNs obtained with sICA were very similar to RSNs retrieved with sICA from functional magnetic resonance imaging data. It still remains to be clarified, however, what technological aspects of hdEEG acquisition and analysis primarily influence this correspondence. Here we examined to what extent the detection of EEG-RSN maps by sICA depends on the electrode density, the accuracy of the head model, and the source localization algorithm employed. Our analyses revealed that the collection of EEG data using a high-density montage is crucial for RSN detection by sICA, but also the use of appropriate methods for head modeling and source localization have a substantial effect on RSN reconstruction. Overall, our results confirm the potential of hdEEG for mapping the functional architecture of the human brain, and highlight at the same time the interplay between acquisition technology and innovative solutions in data analysis. PMID:29551969

Association between urinary symptoms at 7 years old and previous urinary tract infection.

PubMed Central

Hellström, A; Hanson, E; Hansson, S; Hjälmås, K; Jodal, U

1991-01-01

The association between current micturition habits and previous urinary tract infection was analysed among 3553 school entrants aged 7 years by means of a questionnaire. A high incidence of urinary infection, confirmed by urine culture, was found (145 (8.4%) in the 1719 girls and 32 (1.7%) in the 1834 boys). There was a significant association between current symptoms that were suggestive of disturbed bladder function and previous urinary tract infection, but only among girls who were over 3 years of age at the time the first episode was diagnosed. PMID:2001110

Self-perception and malocclusion and their relation to oral appearance and function.

PubMed

Peres, Sílvia Helena de Carvalho Sales; Goya, Suzana; Cortellazzi, Karine Laura; Ambrosano, Gláucia Maria Bovi; Meneghim, Marcelo de Castro; Pereira, Antonio Carlos

2011-10-01

The aim of this study was to evaluate the relationship between malocclusion and self-perception of oral appearance/function, in 12/15-year-old Brazilian adolescents. The cluster sample consisted of 717 teenagers attending 24 urban public (n=611) and 5 rural public (n=107) schools in Maringá/PR. Malocclusion was measured using the Dental Aesthetic Index (DAI), in accordance with WHO recommendations. A parental questionnaire was applied to collect information on esthetic perception level and oral variables related to oral health. Univariate and multiple logistic regression analyses were performed. Multiple logistic regression confirmed that for 12-year-old, missing teeth (OR=2.865) and presence of openbite (open occlusal relationship) (OR=2.865) were risk indicators for speech capability. With regard to 15-year-old, presence of mandibular overjet (horizontal overlap) (OR=4.016) was a risk indicator for speech capability and molar relationship (OR=1.661) was a risk indicator for chewing capability. The impact of malocclusion on adolescents' life was confirmed in this study. Speech and chewing capability were associated with orthodontic deviations, which should be taken into consideration in oral health planning, to identify risk groups and improve community health services.

Age differences in prospective memory for everyday life intentions: A diary approach.

PubMed

Schnitzspahn, Katharina M; Scholz, Urte; Ballhausen, Nicola; Hering, Alexandra; Ihle, Andreas; Lagner, Prune; Kliegel, Matthias

2016-01-01

The age benefit found in many naturalistic prospective memory (PM) tasks has been taken as evidence that PM performance in real life may be spared from aging. However, this conclusion lacks empirical confirmation. Hence, the aim of the present study was to examine possible age differences in the content of everyday PM intentions and their performance. Everyday PM was assessed in young and older adults using a diary approach. Results confirmed a general age benefit for real-life PM tasks. Importantly, this finding was qualified by revealing that the benefit only held true for specific types of intentions such as health and social intentions. Further, moderation analyses showed that the relationships between cognitive functioning and everyday PM were different for young and older adults. While better inhibition, short-term and long-term memory were related with successful PM performance in the young, this was not the case in the older adults. The present findings suggest that the age benefit found in naturalistic experimenter-given tasks extends to real-life PM performance, but may differ depending on the type of intention. Furthermore, cognitive functioning predicts performance in the young, but not in the older adults.

Development of transgenic wheat (Triticum aestivum L.) expressing avidin gene conferring resistance to stored product insects.

PubMed

Abouseadaa, Heba H; Osman, Gamal H; Ramadan, Ahmed M; Hassanein, Sameh E; Abdelsattar, Mohamed T; Morsy, Yasser B; Alameldin, Hussien F; El-Ghareeb, Doaa K; Nour-Eldin, Hanan A; Salem, Reda; Gad, Adel A; Elkhodary, Soheir E; Shehata, Maher M; Mahfouz, Hala M; Eissa, Hala F; Bahieldin, Ahmed

2015-07-22

Wheat is considered the most important cereal crop all over the world. The wheat weevil Sitophilus granarius is a serious insect pests in much of the wheat growing area worldwide and is responsible for significant loss of yield. Avidin proteins has been proposed to function as plant defense agents against insect pests. A synthetic avidin gene was introduced into spring wheat (Triticum aestivum L.) cv. Giza 168 using a biolistic bombardment protocol. The presence and expression of the transgene in six selected T0 transgenic wheat lines were confirmed at the molecular level. Accumulation of avidin protein was detected in transgenic plants compared to non-transgenic plants. Avidin transgene was stably integrated, transcribed and translated as indicated by Southern blot, ELISA, and dot blot analyses, with a high level of expression in transgenic wheat seeds. However, no expression was detected in untransformed wheat seeds. Functional integrity of avidin was confirmed by insect bioassay. The results of bioassay using transgenic wheat plants challenged with wheat weevil revealed 100 % mortality of the insects reared on transgenic plants after 21 days. Transgenic wheat plants had improved resistance to Sitophilus granarius.

Flow properties and chemical composition of carob (Ceratonia siliqua L.) flours as related to particle size and seed presence.

PubMed

Benković, Maja; Belščak-Cvitanović, Ana; Bauman, Ingrid; Komes, Draženka; Srečec, Siniša

2017-10-01

Due to abundance in carbohydrates, dietary fibres and bioactive compounds, as well as for its outspread and low prices, carob (Ceratonia siliqua L.) flour has a great potential of use as a functional ingredient. The aim of this study was to analyse this potential by physical and chemical properties assessment of different particle sizes of carob flour with and without seeds. The influence of seed presence on physical and chemical properties of flour was also investigated. Seed presence in carob flour led to higher cohesivity and cake strength. It also affected the extraction efficiency of polyphenols, which was confirmed by the ranking of samples according to their procyanidin and tannins contents. With regard to the carbohydrate content, significant differences (P<0.05) between the contents of fructose and glucose was established in samples differing by the presence of carob seeds. Spearman rank order correlations revealed a significant difference (P<0.05) between physical and chemical properties of carob flours. These findings confirm the importance of understanding physical and chemical properties of carob flours in order to use them efficiently as a functional food ingredient. Copyright © 2017 Elsevier Ltd. All rights reserved.

Baseline social amotivation predicts 1-year functioning in UHR subjects: A validation and prospective investigation.

PubMed

Lam, Max; Abdul Rashid, Nur Amirah; Lee, Sara-Ann; Lim, Jeanette; Foussias, George; Fervaha, Gagan; Ruhrman, Stephan; Remington, Gary; Lee, Jimmy

2015-12-01

Social amotivation and diminished expression have been reported to underlie negative symptomatology in schizophrenia. In the current study we sought to establish and validate these negative symptom domains in a large cohort of schizophrenia subjects (n=887) and individuals who are deemed to be Ultra-High Risk (UHR) for psychosis. Confirmatory factor analysis conducted on PANSS item domains demonstrate that the dual negative symptom domains exist in schizophrenia and UHR subjects. We further sought to examine if these negative symptom domains were associated with functioning in UHR subjects. Linear regression analyses confirmed that social amotivation predicted functioning in UHR subjects prospectively at 1 year follow up. Results suggest that the association between social amotivation and functioning is generalisable beyond schizophrenia populations to those who are at-risk of developing psychosis. Social amotivation may be an important dimensional clinical construct to be studied across a range of psychiatric conditions. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Liquid crystal nanocomposites produced by mixtures of hydrogen bonded achiral liquid crystals and functionalized carbon nanotubes

NASA Astrophysics Data System (ADS)

Katranchev, B.; Petrov, M.; Keskinova, E.; Naradikian, H.; Rafailov, P. M.; Dettlaff-Weglikowska, U.; Spassov, T.

2014-12-01

The liquid crystalline (LC) nature of alkyloxybenzoic acids is preserved after adding of any mesogenic or non-mesogenic compound through hydrogen bonding. However, this noncovalent interaction provokes a sizable effect on the physical properties as, e. g. melting point and mesomorphic states. In the present work we investigate nanocomposites, prepared by mixture of the eighth homologue of p-n-alkyloxybenzoic acids (8OBA) with single-walled carbon nanotubes (SWCNT) with the purpose to modify the optical properties of the liquid crystal. We exercise optical control on the LC system by inserting SWCNT specially functionalized by carboxylic groups. Since the liquid crystalline state combines order and mobility at the molecular (nanoscale) level, molecular modification can lead to different macroscopical nanocomposite symmetry. The thermal properties of the functionalized nanocomposite are confirmed by DSC analyses. The mechanism of the interaction between surface-treated nanoparticles (functionalized nanotubes) and the liquid crystal 8OBA bent- dimer molecules is briefly discussed.

Enhanced mechanical properties of low-surface energy thin films by simultaneous plasma polymerization of fluorine and epoxy containing polymers

NASA Astrophysics Data System (ADS)

Karaman, Mustafa; Uçar, Tuba

2016-01-01

Thin films of poly(2,2,3,4,4,4 hexafluorobutyl acrylate-glycidyl methacrylate) (P(HFBA-GMA) were deposited on different surfaces using an inductively coupled RF plasma reactor. Fluorinated polymer was used to impart hydrophobicity, whereas epoxy polymer was used for improved durability. The deposition at a low plasma power and temperature was suitable for the functionalization of fragile surfaces such as textile fabrics. The coated rough textile surfaces were found to be superhydrophobic with water contact angles greater than 150° due to the high retention of long fluorinated side chains. The hydrophobicity of the surfaces was observed to be stable after many exposures to ultrasonification tests, which is attributed to the mechanical durability of the films due to their epoxide functionality. FTIR and XPS analyses of the deposited films confirmed that the epoxide functionality of the polymers increased with increasing glycidyl methacrylate fraction in the reactor inlet. The modulus and hardness values of the films also increase with increasing epoxide functionality.

Pathological Confirmation of Optic Neuropathy in Familial Dysautonomia.

PubMed

Mendoza-Santiesteban, Carlos E; Palma, Jose-Alberto; Hedges, Thomas R; Laver, Nora V; Farhat, Nada; Norcliffe-Kaufmann, Lucy; Kaufmann, Horacio

2017-03-01

Clinical data suggest that optic neuropathy and retinal ganglion cell loss are the main cause of visual decline in patients with familial dysautonomia, but this has not previously been confirmed by pathological analyses. We studied retinas and optic nerves in 6 eyes from 3 affected patients obtained at autopsy. Analyses included routine neurohistology and immunohistochemistry for neurofilaments, cytochrome c oxidase (COX), and melanopsin-containing ganglion cells. We observed profound axon loss in the temporal portions of optic nerves with relative preservation in the nasal portions; this correlated with clinical and optical coherence tomography findings in 1 patient. Retinal ganglion cell layers were markedly reduced in the central retina, whereas melanopsin-containing ganglion cells were relatively spared. COX staining was reduced in the temporal portions of the optic nerve indicating reduced mitochondrial density. Axonal swelling with degenerating lysosomes and mitochondria were observed by electron microscopy. These findings support the concept that there is a specific optic neuropathy and retinopathy in patients with familial dysautonomia similar to that seen in other optic neuropathies with mitochondrial dysfunction. This raises the possibility that defective expression of the IkB kinase complex-associated protein (IKAP) resulting from mutations in IKBKAP affects mitochondrial function in the metabolism-dependent retinal parvocellular ganglion cells in this condition. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

Growth and characterization of Bis(L-threonine) copper (II) monohydrate single crystals: A semiorganic second order nonlinear optical material

NASA Astrophysics Data System (ADS)

Subhashini, R.; Sathya, D.; Sivashankar, V.; Latha Mageshwari, P. S.; Arjunan, S.

2016-12-01

Highly transparent solitary nonlinear semiorganic optical material Bis(L-threonine) copper (II) monohydrate [BLTCM], was synthesized by a conventional slow evaporation solution growth technique. The grown crystals were subjected to structural, optical, electrical, thermal, mechanical, SHG and Laser damage threshold studies. Single crystal XRD shows that the material crystallizes in monoclinic system with noncentrosymmetric space group P21. FT-IR and FT-RAMAN analyses confirm the various functional groups present in the grown crystal. The transparency range of BLTCM was determined by UV-vis-NIR studies and various optical constants such as extinction coefficient (K), refractive index, optical conductivity and electric susceptibility with real and imaginary parts of dielectric constant were calculated using the transmittance data which have applications in optoelectronic devices. Dielectric studies of the crystal were carried out at different frequencies and temperatures to analyze the electrical properties. TGA and DSC analyses were performed to study the thermal behaviour of the sample. The hardness stability of the grown specimen was investigated by Vickers microhardness test. The output intensity of second harmonic generation was confirmed using the Kurtz and Perry powder method. The laser induced surface damage threshold of the crystal was measured using Nd:YAG laser.

Nonlinear phenomena in the vocalizations of North Atlantic right whales (Eubalaena glacialis) and killer whales (Orcinus orca).

PubMed

Tyson, Reny B; Nowacek, Douglas P; Miller, Patrick J O

2007-09-01

Nonlinear phenomena or nonlinearities in animal vocalizations include features such as subharmonics, deterministic chaos, biphonation, and frequency jumps that until recently were generally ignored in acoustic analyses. Recent documentation of these phenomena in several species suggests that they may play a communicative role, though the exact function is still under investigation. Here, qualitative descriptions and quantitative analyses of nonlinearities in the vocalizations of killer whales (Orcinus orca) and North Atlantic right whales (Eubalaena glacialis) are provided. All four nonlinear features were present in both species, with at least one feature occurring in 92.4% of killer and 65.7% of right whale vocalizations analyzed. Occurrence of biphonation varied the most between species, being present in 89.0% of killer whale vocalizations and only 20.4% of right whale vocalizations. Because deterministic chaos is qualitatively and quantitatively different than random or Gaussian noise, a program (TISEAN) designed specifically to identify deterministic chaos to confirm the presence of this nonlinearity was used. All segments tested in this software indicate that both species do indeed exhibit deterministic chaos. The results of this study provide confirmation that such features are common in the vocalizations of cetacean species and lay the groundwork for future studies.

Expression, purification, and functional characterization of the insulin-responsive facilitative glucose transporter GLUT4.

PubMed

Kraft, Thomas E; Hresko, Richard C; Hruz, Paul W

2015-12-01

The insulin-responsive facilitative glucose transporter GLUT4 is of fundamental importance for maintenance of glucose homeostasis. Despite intensive effort, the ability to express and purify sufficient quantities of structurally and functionally intact protein for biophysical analysis has previously been exceedingly difficult. We report here the development of novel methods to express, purify, and functionally reconstitute GLUT4 into detergent micelles and proteoliposomes. Rat GLUT4 containing FLAG and His tags at the amino and carboxy termini, respectively, was engineered and stably transfected into HEK-293 cells. Overexpression in suspension culture yielded over 1.5 mg of protein per liter of culture. Systematic screening of detergent solubilized GLUT4-GFP fusion protein via fluorescent-detection size exclusion chromatography identified lauryl maltose neopentyl glycol (LMNG) as highly effective for isolating monomeric GLUT4 micelles. Preservation of structural integrity and ligand binding was demonstrated via quenching of tryptophan fluorescence and competition of ATB-BMPA photolabeling by cytochalasin B. GLUT4 was reconstituted into lipid nanodiscs and proper folding was confirmed. Reconstitution of purified GLUT4 with amphipol A8-35 stabilized the transporter at elevated temperatures for extended periods of time. Functional activity of purified GLUT4 was confirmed by reconstitution of LMNG-purified GLUT4 into proteoliposomes and measurement of saturable uptake of D-glucose over L-glucose. Taken together, these data validate the development of an efficient means to generate milligram quantities of stable and functionally intact GLUT4 that is suitable for a wide array of biochemical and biophysical analyses. © 2015 The Protein Society.

GRAPHIC REANALYSIS OF THE TWO NINDS-TPA TRIALS CONFIRMS SUBSTANTIAL TREATMENT BENEFIT

PubMed Central

Saver, Jeffrey L.; Gornbein, Jeffrey; Starkman, Sidney

2010-01-01

Background of Comment/Review Multiple statistical analyses of the two NINDS-TPA Trials have confirmed study findings of benefit of fibrinolytic therapy. A recent graphic analysis departed from best practices in the visual display of quantitative information by failing to take into account the skewed functional importance NIH Stroke Scale raw scores and by scaling change axes at up to twenty times the range achievable by individual patients. Methods Using the publicly available datasets of the 2 NINDS-TPA Trials, we generated a variety of figures appropriate to the characteristics of acute stroke trial data. Results A diverse array of figures all visually delineated substantial benefits of fibrinolytic therapy, including: bar charts of normalized gain and loss; stacked bar, bar, and matrix plots of clinically relevant ordinal ranks; a time series stacked line plot of continuous scale disability weights; and line plot, bubble chart, and person icon array graphs of joint outcome table analysis. The achievable change figure showed substantially greater improvement among TPA than placebo patients, median 66.7% (IQR 0–92.0) vs 50.0% (IQR −7.1 – 80.0), p=0.003. Conclusions On average, under 3 hour patients treated with TPA recovered two-thirds while placebo patients improved only half of the way towards fully normal. Graphical analyses of the two NINDS-TPA trials, when performed according to best practices, is a useful means of conveying details about patient response to therapy not fully delineated by summary statistics, and confirms a valuable treatment benefit of under 3 hour fibrinolytic therapy in acute stroke. PMID:20829518

Occlusal force is correlated with cognitive function directly as well as indirectly via food intake in community-dwelling older Japanese: From the SONIC study.

PubMed

Ikebe, Kazunori; Gondo, Yasuyuki; Kamide, Kei; Masui, Yukie; Ishizaki, Taturo; Arai, Yasumichi; Inagaki, Hiroki; Nakagawa, Takeshi; Kabayama, Mai; Ryuno, Hirochika; Okubo, Hitomi; Takeshita, Hajime; Inomata, Chisato; Kurushima, Yuko; Mihara, Yusuke; Hatta, Kohdai; Fukutake, Motoyoshi; Enoki, Kaori; Ogawa, Taiji; Matsuda, Ken-Ichi; Sugimoto, Ken; Oguro, Ryosuke; Takami, Yoichi; Itoh, Norihisa; Takeya, Yasushi; Yamamoto, Koichi; Rakugi, Hiromi; Murakami, Shinya; Kitamura, Masahiro; Maeda, Yoshinobu

2018-01-01

Growing evidence suggests that oral health may be an important factor associated with cognitive function in aged populations. However, many previous studies on this topic used insensitive oral indicators or did not include certain essential covariates. Thus, we examined the association between occlusal force and cognitive function in a large sample of older adults, controlling for dietary intake, vascular risk factors, inflammatory biomarkers, depression, and genetic factors. In this cross-sectional study of older community-dwelling Japanese adults, we examined data collected from 994 persons aged 70 years and 968 persons aged 80 years. Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were evaluated according to the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between MoCA-J scores and occlusal force were investigated via bivariate and multivariate analyses. Education level, financial status, depression score, and intake of green and yellow vegetables, as well as number of teeth and occlusal force, were significantly correlated with MoCA-J scores in both age groups. Among individuals aged 80 years, CRP and periodontal status were weakly but significantly associated with MoCA-J score. After controlling for all significant variables via bivariate analyses, the correlation between maximal occlusal force and cognitive function persisted. A path analysis confirmed the hypothesis that cognitive function is associated with occlusal force directly as well as indirectly via food intake. After controlling for possible factors, maximal occlusal force was positively associated with cognitive function directly as well as indirectly through dietary intake.

Expansion of the aminoglycoside-resistance 16S rRNA (m(1)A1408) methyltransferase family: expression and functional characterization of four hypothetical enzymes of diverse bacterial origin.

PubMed

Witek, Marta A; Conn, Graeme L

2014-09-01

The global dissemination, potential activity in diverse species and broad resistance spectrum conferred by the aminoglycoside-resistance ribosomal RNA methyltransferases make them a significant potential new threat to the efficacy of aminoglycoside antibiotics in the treatment of serious bacterial infections. The N1 methylation of adenosine 1408 (m(1)A1408) confers resistance to structurally diverse aminoglycosides, including kanamycin, neomycin and apramycin. The limited analyses to date of the enzymes responsible have identified common features but also potential differences in their molecular details of action. Therefore, with the goal of expanding the known 16S rRNA (m(1)A1408) methyltransferase family as a platform for developing a more complete mechanistic understanding, we report here the cloning, expression and functional analyses of four hypothetical aminoglycoside-resistance rRNA methyltransferases from recent genome sequences of diverse bacterial species. Each of the genes produced a soluble, folded protein with a secondary structure, as determined from circular dichroism (CD) spectra, consistent with enzymes for which high-resolution structures are available. For each enzyme, antibiotic minimum inhibitory concentration (MIC) assays revealed a resistance spectrum characteristic of the known 16S rRNA (m(1)A1408) methyltransferases and the modified nucleotide was confirmed by reverse transcription as A1408. In common with other family members, higher binding affinity for the methylation reaction by-product S-adenosylhomocysteine (SAH) than the cosubstrate S-adenosyl-L-methionine (SAM) was observed for three methyltransferases, while one unexpectedly showed no measurable affinity for SAH. Collectively, these results confirm that each hypothetical enzyme is a functional 16S rRNA (m(1)A1408) methyltransferase but also point to further potential mechanistic variation within this enzyme family. Copyright © 2014 Elsevier B.V. All rights reserved.

Novel poly(dimethylsiloxane) bonding strategy via room temperature "chemical gluing".

PubMed

Lee, Nae Yoon; Chung, Bong Hyun

2009-04-09

Here we propose a new scheme for bonding poly(dimethylsiloxane) (PDMS), namely, a "chemical gluing", at room temperature by anchoring chemical functionalities on the surfaces of PDMS. Aminosilane and epoxysilane are anchored separately on the surfaces of two PDMS substrates, the reaction of which are well-known to form a strong amine-epoxy bond, therefore acting as a chemical glue. The bonding is performed for 1 h at room temperature without employing heat. We characterize the surface properties and composition by contact angle measurement, X-ray photoelectron spectroscopy analysis, and fluorescence measurement to confirm the formation of surface functionalities and investigate the adhesion strength by means of pulling, tearing, and leakage tests. As confirmed by the above-mentioned analyses and tests, PDMS surfaces were successfully modified with amine and epoxy functionalities, and a bonding based on the amine-epoxy chemical gluing was successfully realized within 1 h at room temperature. The bonding was sufficiently robust to tolerate intense introduction of liquid whose per minute injection volume was almost 2000 times larger than the total internal volume of the microchannel used. In addition to the bonding of PDMS-PDMS homogeneous assembly, the bonding of the PDMS-poly(ethylene terephthalate) heterogeneous assembly was also examined. We also investigate the potential use of the multifunctionalized walls inside the microchannel, generated as a consequence of the chemical gluing, as a platform for the targeted immobilization.

Confirmation of the pathogenicity of a mutation p.G337C in the COL1A2 gene associated with osteogenesis imperfecta

PubMed Central

Jia, Mingrui; Shi, Ranran; Zhao, Xuli; Fu, Zhijian; Bai, Zhijing; Sun, Tao; Zhao, Xuejun; Wang, Wenbo; Xu, Chao; Yan, Fang

2017-01-01

Abstract Mutation analysis as the gold standard is particularly important in diagnosis of osteogenesis imperfecta (OI) and it may be preventable upon early diagnosis. In this study, we aimed to analyze the clinical and genetic materials of an OI pedigree as well as to confirm the deleterious property of the mutation. A pedigree with OI was identified. All family members received careful clinical examinations and blood was drawn for genetic analyses. Genes implicated in OI were screened for mutation. The function and structure of the mutant protein were predicted using bioinformatics analysis. The proband, a 9-month fetus, showed abnormal sonographic images. Disproportionately short and triangular face with blue sclera was noticed at birth. She can barely walk and suffered multiple fractures till 2-year old. Her mother appeared small stature, frequent fractures, blue sclera, and deformity of extremities. A heterozygous missense mutation c.1009G>T (p.G337C) in the COL1A2 gene was identified in her mother and her. Bioinformatics analysis showed p.G337 was well-conserved among multiple species and the mutation probably changed the structure and damaged the function of collagen. We suggest that the mutation p.G337C in the COL1A2 gene is pathogenic for OI by affecting the protein structure and the function of collagen. PMID:28953610

Education and dementia in the context of the cognitive reserve hypothesis: a systematic review with meta-analyses and qualitative analyses.

PubMed

Meng, Xiangfei; D'Arcy, Carl

2012-01-01

Cognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer's disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis. We searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21-3.07) and 1.88 (95%CI 1.51-2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology. This systematic review and meta-analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention.

Metaproteomics of cellulose methanisation under thermophilic conditions reveals a surprisingly high proteolytic activity

PubMed Central

Lü, Fan; Bize, Ariane; Guillot, Alain; Monnet, Véronique; Madigou, Céline; Chapleur, Olivier; Mazéas, Laurent; He, Pinjing; Bouchez, Théodore

2014-01-01

Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery from this renewable but recalcitrant material is a key issue. The metaproteome expressed by thermophilic communities during cellulose anaerobic digestion was investigated in microcosms. By multiplying the analytical replicates (65 protein fractions analysed by MS/MS) and relying solely on public protein databases, more than 500 non-redundant protein functions were identified. The taxonomic community structure as inferred from the metaproteomic data set was in good overall agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ hybridisation analyses. Numerous functions related to cellulose and hemicellulose hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor spp. and Clostridium thermocellum were retrieved, indicating their key role in the cellulose-degradation process and also suggesting their complementary action. Despite the abundance of acetate as a major fermentation product, key methanogenesis enzymes from the acetoclastic pathway were not detected. In contrast, enzymes from the hydrogenotrophic pathway affiliated to Methanothermobacter were almost exclusively identified for methanogenesis, suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic methanogenesis. Isotopic analyses confirmed the high dominance of the hydrogenotrophic methanogenesis. Very surprising was the identification of an abundant proteolytic activity from Coprothermobacter proteolyticus strains, probably acting as scavenger and/or predator performing proteolysis and fermentation. Metaproteomics thus appeared as an efficient tool to unravel and characterise metabolic networks as well as ecological interactions during methanisation bioprocesses. More generally, metaproteomics provides direct functional insights at a limited cost, and its attractiveness should increase in the future as sequence databases are growing exponentially. PMID:23949661

Metaproteomics of cellulose methanisation under thermophilic conditions reveals a surprisingly high proteolytic activity.

PubMed

Lü, Fan; Bize, Ariane; Guillot, Alain; Monnet, Véronique; Madigou, Céline; Chapleur, Olivier; Mazéas, Laurent; He, Pinjing; Bouchez, Théodore

2014-01-01

Cellulose is the most abundant biopolymer on Earth. Optimising energy recovery from this renewable but recalcitrant material is a key issue. The metaproteome expressed by thermophilic communities during cellulose anaerobic digestion was investigated in microcosms. By multiplying the analytical replicates (65 protein fractions analysed by MS/MS) and relying solely on public protein databases, more than 500 non-redundant protein functions were identified. The taxonomic community structure as inferred from the metaproteomic data set was in good overall agreement with 16S rRNA gene tag pyrosequencing and fluorescent in situ hybridisation analyses. Numerous functions related to cellulose and hemicellulose hydrolysis and fermentation catalysed by bacteria related to Caldicellulosiruptor spp. and Clostridium thermocellum were retrieved, indicating their key role in the cellulose-degradation process and also suggesting their complementary action. Despite the abundance of acetate as a major fermentation product, key methanogenesis enzymes from the acetoclastic pathway were not detected. In contrast, enzymes from the hydrogenotrophic pathway affiliated to Methanothermobacter were almost exclusively identified for methanogenesis, suggesting a syntrophic acetate oxidation process coupled to hydrogenotrophic methanogenesis. Isotopic analyses confirmed the high dominance of the hydrogenotrophic methanogenesis. Very surprising was the identification of an abundant proteolytic activity from Coprothermobacter proteolyticus strains, probably acting as scavenger and/or predator performing proteolysis and fermentation. Metaproteomics thus appeared as an efficient tool to unravel and characterise metabolic networks as well as ecological interactions during methanisation bioprocesses. More generally, metaproteomics provides direct functional insights at a limited cost, and its attractiveness should increase in the future as sequence databases are growing exponentially.

Coping with missing data in phase III pivotal registration trials: Tolvaptan in subjects with kidney disease, a case study.

PubMed

Ouyang, John; Carroll, Kevin J; Koch, Gary; Li, Junfang

2017-07-01

Missing data cause challenging issues, particularly in phase III registration trials, as highlighted by the European Medicines Agency (EMA) and the US National Research Council. We explore, as a case study, how the issues from missing data were tackled in a double-blind phase III trial in subjects with autosomal dominant polycystic kidney disease. A total of 1445 subjects were randomized in a 2:1 ratio to receive active treatment (tolvaptan), or placebo. The primary outcome, the rate of change in total kidney volume, favored tolvaptan (P < .0001). The key secondary efficacy endpoints of clinical progression of disease and rate of decline in kidney function also favored tolvaptan. However, as highlighted by Food and Drug Administration and EMA, the interpretation of results was hampered by a high number of unevenly distributed dropouts, particularly early dropouts. In this paper, we outline the analyses undertaken to address the issue of missing data thoroughly. "Tipping point analyses" were performed to explore how extreme and detrimental outcomes among subjects with missing data must be to overturn the positive treatment effect attained in those subjects who had complete data. Nonparametric rank-based analyses were also performed accounting for missing data. In conclusion, straightforward and transparent analyses directly taking into account missing data convincingly support the robustness of the preplanned analyses on the primary and secondary endpoints. Tolvaptan was confirmed to be effective in slowing total kidney volume growth, which is considered an efficacy endpoint by EMA, and in lessening the decline in renal function in patients with autosomal dominant polycystic kidney disease. Copyright © 2017 John Wiley & Sons, Ltd.

A Health Assessment Survey of Veteran Students: Utilizing a Community College-Veterans Affairs Medical Center Partnership.

PubMed

Misra-Hebert, Anita D; Santurri, Laura; DeChant, Richard; Watts, Brook; Sehgal, Ashwini R; Aron, David C

2015-10-01

To assess health status among student veterans at a community college utilizing a partnership between a Veterans Affairs Medical Center and a community college. Student veterans at Cuyahoga Community College in Cleveland, Ohio, in January to April 2013. A health assessment survey was sent to 978 veteran students. Descriptive analyses to assess prevalence of clinical diagnoses and health behaviors were performed. Logistic regression analyses were performed to assess for independent predictors of functional limitations. 204 students participated in the survey (21% response rate). Self-reported depression and unhealthy behaviors were high. Physical and emotional limitations (45% and 35%, respectively), and pain interfering with work (42%) were reported. Logistic regression analyses confirmed the independent association of self-reported depression with functional limitation (odds ratio [OR] = 3.3, 95% confidence interval [CI] 1.4-7.8, p < 0.05, and C statistic 0.72) and of post-traumatic stress disorder with pain interfering with work (OR 3.9, CI 1.1-13.6, p < 0.05, and C statistic 0.75). A health assessment survey identified priority areas to inform targeted health promotion for student veterans at a community college. A partnership between a Veterans Affairs Medical Center and a community college can be utilized to help understand the health needs of veteran students. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Does whole blood coagulation analysis reflect developmental haemostasis?

PubMed

Ravn, Hanne Berg; Andreasen, Jo Bønding; Hvas, Anne-Mette

2017-04-01

: Developmental haemostasis has been well documented over the last 3 decades and age-dependent reference ranges have been reported for a number of plasmatic coagulation parameters. With the increasing use of whole blood point-of-care tests like rotational thromboelastometry (ROTEM) and platelet function tests, an evaluation of age-dependent changes is warranted for these tests as well. We obtained blood samples from 149 children, aged 1 day to 5.9 years, and analysed conventional plasmatic coagulation tests, including activated partial prothrombin time, prothrombin time, and fibrinogen (functional). Whole blood samples were analysed using ROTEM to assess overall coagulation capacity and Multiplate analyzer to evaluate platelet aggregation. Age-dependent changes were analysed for all variables. We found age-dependent differences in all conventional coagulation tests (all P values < 0.05), but there was no sign of developmental changes in whole blood coagulation assessment when applying ROTEM, apart from clotting time in the EXTEM assay (P < 0.03). Despite marked differences in mean platelet aggregation between age groups, data did not reach statistical significance. Citrate-anticoagulated blood showed significantly reduced platelet aggregation compared with blood anticoagulated with heparin or hirudin (all P values < 0.003). We confirmed previous developmental changes in conventional plasmatic coagulation test. However, these age-dependent changes were not displayed in whole blood monitoring using ROTEM or Multiplate analyzer. Type of anticoagulant had a significant influence on platelet aggregation across all age groups.

Diagrams for comprehensive molecular orbital-based chemical reaction analyses: reactive orbital energy diagrams.

PubMed

Tsuneda, Takao; Singh, Raman Kumar; Chattaraj, Pratim Kumar

2018-05-15

Reactive orbital energy diagrams are presented as a tool for comprehensively performing orbital-based reaction analyses. The diagrams rest on the reactive orbital energy theory, which is the expansion of conceptual density functional theory (DFT) to an orbital energy-based theory. The orbital energies on the intrinsic reaction coordinates of fundamental reactions are calculated by long-range corrected DFT, which is confirmed to provide accurate orbital energies of small molecules, combining with a van der Waals (vdW) correlation functional, in order to examine the vdW effect on the orbital energies. By analysing the reactions based on the reactive orbital energy theory using these accurate orbital energies, it is found that vdW interactions significantly affect the orbital energies in the initial reaction processes and that more than 70% of reactions are determined to be initially driven by charge transfer, while the remaining structural deformation (dynamics)-driven reactions are classified into identity, cyclization and ring-opening, unimolecular dissociation, and H2 reactions. The reactive orbital energy diagrams, which are constructed using these results, reveal that reactions progress so as to delocalize the occupied reactive orbitals, which are determined as contributing orbitals and are usually not HOMOs, by hybridizing the unoccupied reactive orbitals, which are usually not LUMOs. These diagrams also raise questions about conventional orbital-based diagrams such as frontier molecular orbital diagrams, even for the well-established interpretation of Diels-Alder reactions.

Sense of coherence and disability and the relationship with life satisfaction 6-15 years after traumatic brain injury in northern Sweden.

PubMed

Jacobsson, L J; Westerberg, M; Malec, J F; Lexell, J

2011-06-01

The objective of the study was to assess sense of coherence (SOC) many years after traumatic brain injury (TBI) and explore the relationship between SOC and self-rated life satisfaction (LS) as well as measures of functioning and disability, sex, age at injury, injury severity and time post-injury. Sixty-six individuals (aged 18-65 years) who were 6-15 years post-injury were interviewed. Data on SOC (SOC-13 item scale), measures of functioning and disability (Mayo-Portland Adaptability Inventory, MPAI-4), LS (Satisfaction with Life Scale, SWLS), and sex, age at injury, injury severity and time post-injury were analysed with hierarchical multiple regression analyses. The results showed that SOC in the study group did not differ from the general population and was strongly associated with LS. Regression analyses revealed that emotional factors, social participation, SOC, and time since injury, were more influential than sex, age at injury, and injury severity in explaining LS. It was concluded that SOC in this group of individuals with TBI who were many years post-injury was similar to nondisabled individuals. SOC, together with emotional factors, social participation and injury-related factors, were determinants of LS. These results confirm that LS after TBI is a complex phenomenon dependent on several factors that are important targets for rehabilitation professionals.

Cognitive and Psychosocial Consequences of Hurricanes Katrina and Rita Among Middle-Aged, Older, and Oldest-Old Adults in the Louisiana Healthy Aging Study (LHAS)1

PubMed Central

Cherry, Katie E.; Su, L. Joseph; Welsh, David A.; Galea, Sandro; Jazwinski, S. Michal; Silva, Jennifer L.; Erwin, Marla J.

2010-01-01

This study examined the impact of Hurricanes Katrina and Rita on cognitive and psychosocial functioning among middle-aged (45–64 years), older (65–89 years) and oldest-old adults (90 years and over) in the Louisiana Healthy Aging Study (LHAS). Analyses of pre- and post-disaster cognitive data showed storm-related decrements in working memory for the middle-aged and older adults, but not for the oldest-old adults. Regression analyses confirmed that measures of social engagement and storm-related disruption significantly predicted pre- to post-disaster differences in short-term and working memory performance for the middle-aged and older adults only. These results are consistent with a burden perspective on post-disaster psychological reactions. Implications for current views of disaster reactions are discussed. PMID:21461124

Motion cue effects on human pilot dynamics in manual control

NASA Technical Reports Server (NTRS)

Washizu, K.; Tanaka, K.; Endo, S.; Itoko, T.

1977-01-01

Two experiments were conducted to study the motion cue effects on human pilots during tracking tasks. The moving-base simulator of National Aerospace Laboratory was employed as the motion cue device, and the attitude director indicator or the projected visual field was employed as the visual cue device. The chosen controlled elements were second-order unstable systems. It was confirmed that with the aid of motion cues the pilot workload was lessened and consequently the human controllability limits were enlarged. In order to clarify the mechanism of these effects, the describing functions of the human pilots were identified by making use of the spectral and the time domain analyses. The results of these analyses suggest that the sensory system of the motion cues can yield the differential informations of the signal effectively, which coincides with the existing knowledges in the physiological area.

Immunogenicity is preferentially induced in sparse dendritic cell cultures.

PubMed

Nasi, Aikaterini; Bollampalli, Vishnu Priya; Sun, Meng; Chen, Yang; Amu, Sylvie; Nylén, Susanne; Eidsmo, Liv; Rothfuchs, Antonio Gigliotti; Réthi, Bence

2017-03-09

We have previously shown that human monocyte-derived dendritic cells (DCs) acquired different characteristics in dense or sparse cell cultures. Sparsity promoted the development of IL-12 producing migratory DCs, whereas dense cultures increased IL-10 production. Here we analysed whether the density-dependent endogenous breaks could modulate DC-based vaccines. Using murine bone marrow-derived DC models we show that sparse cultures were essential to achieve several key functions required for immunogenic DC vaccines, including mobility to draining lymph nodes, recruitment and massive proliferation of antigen-specific CD4+ T cells, in addition to their TH1 polarization. Transcription analyses confirmed higher commitment in sparse cultures towards T cell activation, whereas DCs obtained from dense cultures up-regulated immunosuppressive pathway components and genes suggesting higher differentiation plasticity towards osteoclasts. Interestingly, we detected a striking up-regulation of fatty acid and cholesterol biosynthesis pathways in sparse cultures, suggesting an important link between DC immunogenicity and lipid homeostasis regulation.

Morphogenetic Alterations in Melipona quadrifasciata anthidioides (Hymenoptera: Apidae) Associated with Pesticides.

PubMed

Prado-Silva, Arlete; Nunes, Lorena Andrade; Dos Santos, Jádilla Mendes; Affonso, Paulo Roberto Antunes de Mello; Waldschmidt, Ana Maria

2018-05-01

Bees are major pollinators of both native flora and cultured crops. Nonetheless, despite their key functional role in ecosystems and agriculture, bee populations have been affected worldwide by deforestation and contamination by insecticides. Conversely, little is known about the effects of pesticides on morphogenetic development of neotropical stingless bees. We compared the fluctuating asymmetry (FA) in newly emerged bees and foragers of Melipona quadrifasciata anthidioides exposed to pesticides (experimental greenhouse and cultivated field). In addition, visitation behavior of foragers was inferred from pollen analyses and direct observation. A significant increase of FA (P < 0.001) was detected in bees from the greenhouse. Even though pesticides might affect their development, foragers seem to avoid contaminated plants whenever possible, as confirmed by pollen and visitation analyses. Consequently, the conservation of natural forests in agricultural landscapes is essential to ensure the health of colonies in stingless bees.

Differentiation of depression and anxiety groups using defense mechanisms.

PubMed

Olson, Trevor R; Presniak, Michelle D; MacGregor, Michael Wm

2009-11-01

We examined whether participants in depressed and anxious groups could be classified correctly using observer and self-report measures of defense mechanisms. A sample of 1182 university students completed the Personality Assessment Inventory and those scoring in the clinical range on either depression or anxiety indices were selected for participation. In total, 25 participants met criteria for the depressed group and 94 met criteria for the anxious group. Individual defense scores from the Defense-Q and the Defense Style Questionnaire were separately entered into 2 stepwise discriminant analyses. After cross-validation, the Defense-Q and Defense Style Questionnaire analyses classified participants with 75.0% and 71.3% accuracy, respectively. The results indicated that depression and anxiety groups can be significantly differentiated by defense use alone. Important differences in defensive functioning between these groups were confirmed and differences between observer and self-report measures of defenses mechanisms and current challenges in defense research were highlighted.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

PubMed Central

Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; p<0.0001), but not females (r=0.44; p=0.15), potentially related to observed dysregulation of the miR-29 family in the lung. These findings highlight the role of oxidative stress in COPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Serum chemerin levels are independently associated with quality of life in colorectal cancer survivors: A pilot study

PubMed Central

Lee, Jee-Yon; Lee, Mi-Kyung; Kim, Nam-Kyu; Chu, Sang-Hui; Lee, Duk-Chul; Lee, Hye-Sun

2017-01-01

Background Colorectal cancer (CRC) survivors are known to experience various symptoms that significantly affect their quality of life (QOL); therefore, it is important to identify clinical markers related with CRC survivor QOL. Here we investigated the relationship between serum chemerin levels, a newly identified proinflammatory adipokine, and QOL in CRC survivors. Methods A data of total of 110 CRC survivors were analysed in the study. Serum chemerin levels were measured with an enzyme immunoassay analyser. Functional Assessment of Cancer Therapy (FACT) scores were used as an indicator of QOL in CRC survivors. Results Weak but not negligible relationships were observed between serum chemerin levels and FACT-General (G) (r = -0.22, p<0.02), FACT-Colorectal cancer (C) (r = -0.23, p<0.02) and FACT-Fatigue (F) scores (r = -0.27, p<0.01) after adjusting for confounding factors. Both stepwise and enter method multiple linear regression analyses confirmed that serum chemerin levels were independently associated with FACT-G (stepwise: β = -0.15, p<0.01; enter: β = -0.12, p = 0.02), FACT-C (stepwise: β = -0.19, p<0.01; enter; β = -0.14, p = 0.02) and FACT-F scores (stepwise: β = -0.23, p<0.01; enter: β = -0.20, p<0.01). Conclusions Our results demonstrate a weak inverse relationship between serum chemerin and CRC survivor QOL. Although it is impossible to determine causality, our findings suggest that serum chemerin levels may have a significant association with CRC survivor QOL. Further prospective studies are required to confirm the clinical significance of our pilot study. PMID:28475614

Experimental and theoretical investigations of non-centrosymmetric 8-hydroxyquinolinium dibenzoyl-(L)-tartrate methanol monohydrate single crystal

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

Sudharsana, N.; Krishnakumar, V.; Nagalakshmi, R., E-mail: nagaphys@yahoo.com

Graphical abstract: ORTEP diagram of HQDBT. - Highlights: • Single crystal XRD and NMR studies confirm the formation of the title compound. • SHG efficiency was found to be 0.6 times that of KDP. • First-order hyperpolarizability (β) was calculated using HF and B3LYP methods. - Abstract: A novel 8-hydroxyquinolinium dibenzoyl-(L)-tartrate methanol monohydrate crystal has been grown by slow evaporation technique. The single crystal X-ray diffraction analysis has been done for the title compound and is found to crystallize in orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}. The optical absorption cut-off wavelength is found to be 440 nm. The vibrationalmore » analysis has been carried out to assess the functional groups present in the title compound. The molecular structure of the title compound has been confirmed by nuclear magnetic resonance spectroscopy. Thermogravimetric, differential scanning calorimetric and differential thermal analyses reveal the melting point and thermal stability of the title compound. The second harmonic generation efficiency is confirmed by Kurtz–Perry powder technique. Further quantum chemical calculations are performed using Gaussian 03 software.« less

Screening and structural elucidation of the zwitterionic cocrystal o-picolinic acid with p-nitro aniline

NASA Astrophysics Data System (ADS)

Mekala, R.; Jagdish, P.; Mathammal, R.; Sangeetha, K.

2017-04-01

The cocrystal was screened by solvent drop grinding method and the crystals were grown by slow evaporation method at ambient conditions. The cocrystal formation of o-picolinic acid with p-nitro aniline was initially analysed by powder X-ray diffraction. Further the structural properties of the grown crystal were confirmed by the single X-ray diffraction which indicates that the cocrystal were connected by the strong N+sbnd H-⋯O hydrogen bond interaction. The cell parameters of the grown crystal were a = 14.2144(5) Å, b = 5.7558(2) Å, c = 16.0539(6) Å. The functional groups were identified using Fourier transform infrared and Raman spectral analysis. The excitation and emission state of the sample was analysed by the UV-Visible and Fluorescence studies. The red emission was observed from the Fluorescence studies. NMR studies revealed the chemical shift of the cocrystal. Thermal stability and its melting behaviour were studied by TGA and DSC analytical techniques. Electrical behaviour was studied using the dielectric studies. The intermolecular charge transfer within the molecule were analysed using HOMO- LUMO plots.

Chemical bonding analysis on amphoteric hydrogen - alkaline earth ammine borohydrides

NASA Astrophysics Data System (ADS)

Kiruthika, S.; Ravindran, P.

2018-04-01

Usually the ions in solid are in the positive oxidation states or in the negative oxidation state depending upon the chemical environment. It is highly unusual for an ion having both positive as well as negative oxidation state in a particular compound. Structural analysis suggest that the alkaline earth ammine borohydrides (AABH) with the chemical formula M (BH4)2(NH3)2 (M = Mg, Ca, or Sr) where hydrogen is present in +1 and -1 oxidation states. In order to understand the oxidation states of hydrogen and also the character of chemical bond present in AABH we have made charge density, electron localization function, Born effective charge, Bader effective charge, and density of states analyses using result from the density functional calculations. Our detailed analyses show that hydrogen is in amphoteric behavior with hydrogen closer to boron is in negative oxidation state and that closer to nitrogen is in the positive oxidation state. Due to the presence of finite covalent bonding between the consitutents in AABH the oxidation state of hydrogen is non-interger value. The confirmation of the presence of amphtoric behavior of hydrogen in AABH has implication in hydrogen storage applications.

Flavonoids Suppress Pseudomonas aeruginosa Virulence through Allosteric Inhibition of Quorum-sensing Receptors*

PubMed Central

Paczkowski, Jon E.; Mukherjee, Sampriti; McCready, Amelia R.; Cong, Jian-Ping; Aquino, Christopher J.; Kim, Hahn; Henke, Brad R.; Smith, Chari D.; Bassler, Bonnie L.

2017-01-01

Quorum sensing is a process of cell-cell communication that bacteria use to regulate collective behaviors. Quorum sensing depends on the production, detection, and group-wide response to extracellular signal molecules called autoinducers. In many bacterial species, quorum sensing controls virulence factor production. Thus, disrupting quorum sensing is considered a promising strategy to combat bacterial pathogenicity. Several members of a family of naturally produced plant metabolites called flavonoids inhibit Pseudomonas aeruginosa biofilm formation by an unknown mechanism. Here, we explore this family of molecules further, and we demonstrate that flavonoids specifically inhibit quorum sensing via antagonism of the autoinducer-binding receptors, LasR and RhlR. Structure-activity relationship analyses demonstrate that the presence of two hydroxyl moieties in the flavone A-ring backbone are essential for potent inhibition of LasR/RhlR. Biochemical analyses reveal that the flavonoids function non-competitively to prevent LasR/RhlR DNA binding. Administration of the flavonoids to P. aeruginosa alters transcription of quorum sensing-controlled target promoters and suppresses virulence factor production, confirming their potential as anti-infectives that do not function by traditional bacteriocidal or bacteriostatic mechanisms. PMID:28119451

Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.

PubMed

Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant; Eriksson, Johan G; Espeseth, Thomas; Freimer, Nelson A; Giakoumaki, Stella; Giegling, Ina; Gill, Michael; Glahn, David C; Hariri, Ahmad R; Hatzimanolis, Alex; Keller, Matthew C; Knowles, Emma; Koltai, Deborah; Konte, Bettina; Lahti, Jari; Le Hellard, Stephanie; Lencz, Todd; Liewald, David C; London, Edythe; Lundervold, Astri J; Malhotra, Anil K; Melle, Ingrid; Morris, Derek; Need, Anna C; Ollier, William; Palotie, Aarno; Payton, Antony; Pendleton, Neil; Poldrack, Russell A; Räikkönen, Katri; Reinvang, Ivar; Roussos, Panos; Rujescu, Dan; Sabb, Fred W; Scult, Matthew A; Smeland, Olav B; Smyrnis, Nikolaos; Starr, John M; Steen, Vidar M; Stefanis, Nikos C; Straub, Richard E; Sundet, Kjetil; Tiemeier, Henning; Voineskos, Aristotle N; Weinberger, Daniel R; Widen, Elisabeth; Yu, Jin; Abecasis, Goncalo; Andreassen, Ole A; Breen, Gerome; Christiansen, Lene; Debrabant, Birgit; Dick, Danielle M; Heinz, Andreas; Hjerling-Leffler, Jens; Ikram, M Arfan; Kendler, Kenneth S; Martin, Nicholas G; Medland, Sarah E; Pedersen, Nancy L; Plomin, Robert; Polderman, Tinca J C; Ripke, Stephan; van der Sluis, Sophie; Sullivan, Patrick F; Vrieze, Scott I; Wright, Margaret J; Posthuma, Danielle

2018-06-25

Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7 , but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.

The semantic and episodic subcomponents of famous person knowledge: dissociation in healthy subjects.

PubMed

Piolino, Pascale; Lamidey, Virginie; Desgranges, Béatrice; Eustache, Francis

2007-01-01

Fifty-two subjects between ages 40 and 79 years were administered a questionnaire assessing their ability to recall semantic information about famous people from 4 different decades and to recollect its episodic source of acquisition together with autonoetic consciousness via the remember-know paradigm. In addition, they underwent a battery of standardized neuropsychological tests to assess episodic and semantic memory and executive functions. The analyses of age reveal differences for the episodic source score but no differences between age groups for the semantic scores within each decade. Regardless of the age of people, the analyses also show that semantic memory subcomponents of the famous person test are highly associated with each other as well as with the source component. The recall of semantic information on the famous person test relies on participants' semantic abilities, whereas the recall of its episodic source depends on their executive functions. The present findings confirm the existence of an episodic-semantic distinction in knowledge about famous people. They provide further evidence that personal source and semantic information are at once distinct and highly interactive within the framework of remote memory. (c) 2007 APA, all rights reserved.

Molecular characterization of a microbial consortium involved in methane oxidation coupled to denitrification under micro-aerobic conditions

PubMed Central

Liu, Jingjing; Sun, Faqian; Wang, Liang; Ju, Xi; Wu, Weixiang; Chen, Yingxu

2014-01-01

Methane can be used as an alternative carbon source in biological denitrification because it is nontoxic, widely available and relatively inexpensive. A microbial consortium involved in methane oxidation coupled to denitrification (MOD) was enriched with nitrite and nitrate as electron acceptors under micro-aerobic conditions. The 16S rRNA gene combined with pmoA phylogeny of methanotrophs and nirK phylogeny of denitrifiers were analysed to reveal the dominant microbial populations and functional microorganisms. Real-time quantitative polymerase chain reaction results showed high numbers of methanotrophs and denitrifiers in the enriched consortium. The 16S rRNA gene clone library revealed that Methylococcaceae and Methylophilaceae were the dominant populations in the MOD ecosystem. Phylogenetic analyses of pmoA gene clone libraries indicated that all methanotrophs belonged to Methylococcaceae, a type I methanotroph employing the ribulose monophosphate pathway for methane oxidation. Methylotrophic denitrifiers of the Methylophilaceae that can utilize organic intermediates (i.e. formaldehyde, citrate and acetate) released from the methanotrophs played a vital role in aerobic denitrification. This study is the first report to confirm micro-aerobic denitrification and to make phylogenetic and functional assignments for some members of the microbial assemblages involved in MOD. PMID:24245852

Initial evaluation of discrete orthogonal basis reconstruction of ECT images

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

Moody, E.B.; Donohue, K.D.

1996-12-31

Discrete orthogonal basis restoration (DOBR) is a linear, non-iterative, and robust method for solving inverse problems for systems characterized by shift-variant transfer functions. This simulation study evaluates the feasibility of using DOBR for reconstructing emission computed tomographic (ECT) images. The imaging system model uses typical SPECT parameters and incorporates the effects of attenuation, spatially-variant PSF, and Poisson noise in the projection process. Sample reconstructions and statistical error analyses for a class of digital phantoms compare the DOBR performance for Hartley and Walsh basis functions. Test results confirm that DOBR with either basis set produces images with good statistical properties. Nomore » problems were encountered with reconstruction instability. The flexibility of the DOBR method and its consistent performance warrants further investigation of DOBR as a means of ECT image reconstruction.« less

Longitudinal Assessment of Cognitive and Psychosocial Functioning After Hurricanes Katrina and Rita: Exploring Disaster Impact on Middle-Aged, Older, and Oldest-Old Adults.

PubMed

Cherry, Katie E; Brown, Jennifer Silva; Marks, Loren D; Galea, Sandro; Volaufova, Julia; Lefante, Christina; Su, L Joseph; Welsh, David A; Jazwinski, S Michal

2011-12-01

The authors examined the effects of Hurricanes Katrina and Rita (HKR) on cognitive and psychosocial functioning in a lifespan sample of adults 6 to 14 months after the storms. Participants were recruited from the Louisiana Healthy Aging Study (LHAS). Most were assessed during the immediate impact period and retested for this study. Analyses of pre-and post-disaster cognitive data confirmed that storm-related decrements in working memory for middle-aged and older adults observed in the immediate impact period had returned to pre-hurricane levels in the post-disaster recovery period. Middle-aged adults reported more storm-related stressors and greater levels of stress than the two older groups at both waves of testing. These results are consistent with a burden perspective on post-disaster psychological reactions.

Effects of repeated doses of caffeine on performance and alertness: new data and secondary analyses.

PubMed

Hewlett, Paul; Smith, Andrew

2007-08-01

The effects of caffeine on mood and performance are well established. Some authors suggest that caffeine merely reverses effects of caffeine withdrawal rather than having direct behavioural effects. It has also been suggested that withdrawal may be removed by a first dose of caffeine and further doses have little subsequent effect. These issues are examined here. The present study aimed to determine whether caffeine withdrawal influenced mood and performance by comparing regular consumers who had been withdrawn from caffeine overnight with non-consumers. Following this repeated caffeine doses were administered to test the claim that repeated dosing has no extra effect on mood or performance. Secondary analyses of data collected after a day of normal caffeine consumption were also carried out to examine some alternative explanations of their results which showed effects of caffeine after a day of normal caffeine consumption. One hundred and twenty volunteers participated in the study. Regular caffeine consumption was assessed by questionnaire and this showed that 36 of the volunteers did not regularly consume caffeinated beverages. Volunteers were instructed to abstain from caffeine overnight and then completed a baseline session measuring mood and a range of cognitive functions at 08.00 the next day. Following this volunteers were given 0, or 1 mg/kg caffeine in a milkshake, glucose solution or water (at 09:00), followed by a second 0 or 1 mg/kg caffeine dose (at 09:40) and the test battery repeated at 10:00. The baseline data showed no effect of overnight caffeine withdrawal on mood or performance. In contrast, caffeine challenge improved vigilance performance and prevented decreases in alertness induced by completion of the task battery. The magnitude of these effects increased as a function of the number of doses of caffeine given. Secondary analyses of data from Christopher et al. (2003) also confirmed that effects of caffeine did not depend on length of withdrawal. The present findings show no effect of overnight caffeine withdrawal on mood and performance. Caffeine challenge did have the predicted effect on alertness and vigilance, with the size of the effects increasing with caffeine dose. These findings suggest that the effects of caffeine are not due to reversal of effects of withdrawal, a view confirmed by secondary analyses of data collected after a day of normal caffeine consumption. Copyright 2007 John Wiley & Sons, Ltd.

Prokaryotic regulatory systems biology: Common principles governing the functional architectures of Bacillus subtilis and Escherichia coli unveiled by the natural decomposition approach.

PubMed

Freyre-González, Julio A; Treviño-Quintanilla, Luis G; Valtierra-Gutiérrez, Ilse A; Gutiérrez-Ríos, Rosa María; Alonso-Pavón, José A

2012-10-31

Escherichia coli and Bacillus subtilis are two of the best-studied prokaryotic model organisms. Previous analyses of their transcriptional regulatory networks have shown that they exhibit high plasticity during evolution and suggested that both converge to scale-free-like structures. Nevertheless, beyond this suggestion, no analyses have been carried out to identify the common systems-level components and principles governing these organisms. Here we show that these two phylogenetically distant organisms follow a set of common novel biologically consistent systems principles revealed by the mathematically and biologically founded natural decomposition approach. The discovered common functional architecture is a diamond-shaped, matryoshka-like, three-layer (coordination, processing, and integration) hierarchy exhibiting feedback, which is shaped by four systems-level components: global transcription factors (global TFs), locally autonomous modules, basal machinery and intermodular genes. The first mathematical criterion to identify global TFs, the κ-value, was reassessed on B. subtilis and confirmed its high predictive power by identifying all the previously reported, plus three potential, master regulators and eight sigma factors. The functionally conserved cores of modules, basal cell machinery, and a set of non-orthologous common physiological global responses were identified via both orthologous genes and non-orthologous conserved functions. This study reveals novel common systems principles maintained between two phylogenetically distant organisms and provides a comparison of their lifestyle adaptations. Our results shed new light on the systems-level principles and the fundamental functions required by bacteria to sustain life. Copyright © 2012 Elsevier B.V. All rights reserved.

Determinants of Occupational and Residential Functioning in Bipolar Disorder

PubMed Central

Depp, Colin A; Mausbach, Brent T; Bowie, Christopher; Wolyniec, Paula; Thornquist, Mary H.; Luke, James R.; McGrath, John A.; Pulver, Ann E.; Harvey, Philip D.; Patterson, Thomas L

2013-01-01

Background Bipolar disorder is associated with reduced rates of employment and residential independence. The influence of cognitive impairment and affective symptoms on these functional attainments has received little previous attention and is the focus of this study. Method A total of 229 adult outpatients with bipolar disorder without active substance use disorders and with an average of mild severity of affective symptoms were included in the analyses. After adjusting for sociodemographic and illness history covariates, univariate and multivariate analyses were used to evaluate the independent and interactive associations of neurocognitive ability, performance-based functional capacity, and affective symptom severity with residential independence, occupational status and number of hours worked. Results A total of 30% of the sample was unemployed and 18% were not independently residing. Neurocognitive ability was the strongest predictor of any employment, but depressive symptom severity was the only variable significantly related to hours worked. The strongest predictor of residential independence was performance-based functional capacity. Affective symptoms and neurocognitive ability were independent (non-interactive) predictors of occupational and residential status. Limitations This is a cross-sectional study and thus causal direction among variables is unknown. The sample was ethnically homogeneous and thus the results may not generalize to ethnically diverse samples. Conclusions This study confirmed elevated rates of unemployment and residential non-independence in adults with bipolar disorder. Interventions targeting cognitive deficits and functional capacity may increase the likelihood of any employment or residential independence, respectively. Interventions targeting depressive symptoms may be most influential on work outcomes among those already employed. PMID:22129770

Algebraic Topology of Multi-Brain Connectivity Networks Reveals Dissimilarity in Functional Patterns during Spoken Communications

PubMed Central

Tadić, Bosiljka; Andjelković, Miroslav; Boshkoska, Biljana Mileva; Levnajić, Zoran

2016-01-01

Human behaviour in various circumstances mirrors the corresponding brain connectivity patterns, which are suitably represented by functional brain networks. While the objective analysis of these networks by graph theory tools deepened our understanding of brain functions, the multi-brain structures and connections underlying human social behaviour remain largely unexplored. In this study, we analyse the aggregate graph that maps coordination of EEG signals previously recorded during spoken communications in two groups of six listeners and two speakers. Applying an innovative approach based on the algebraic topology of graphs, we analyse higher-order topological complexes consisting of mutually interwoven cliques of a high order to which the identified functional connections organise. Our results reveal that the topological quantifiers provide new suitable measures for differences in the brain activity patterns and inter-brain synchronisation between speakers and listeners. Moreover, the higher topological complexity correlates with the listener’s concentration to the story, confirmed by self-rating, and closeness to the speaker’s brain activity pattern, which is measured by network-to-network distance. The connectivity structures of the frontal and parietal lobe consistently constitute distinct clusters, which extend across the listener’s group. Formally, the topology quantifiers of the multi-brain communities exceed the sum of those of the participating individuals and also reflect the listener’s rated attributes of the speaker and the narrated subject. In the broader context, the presented study exposes the relevance of higher topological structures (besides standard graph measures) for characterising functional brain networks under different stimuli. PMID:27880802

Shifts in taxonomic and functional microbial diversity with agriculture: How fragile is the Brazilian Cerrado?

PubMed

Souza, Renata Carolini; Mendes, Iêda Carvalho; Reis-Junior, Fábio Bueno; Carvalho, Fabíola Marques; Nogueira, Marco Antonio; Vasconcelos, Ana Tereza Ribeiro; Vicente, Vânia Aparecida; Hungria, Mariangela

2016-03-16

The Cerrado--an edaphic type of savannah--comprises the second largest biome of the Brazilian territory and is the main area for grain production in the country, but information about the impact of land conversion to agriculture on microbial diversity is still scarce. We used a shotgun metagenomic approach to compare undisturbed (native) soil and soils cropped for 23 years with soybean/maize under conservation tillage--"no-till" (NT)--and conventional tillage (CT) systems in the Cerrado biome. Soil management and fertilizer inputs with the introduction of agriculture improved chemical properties, but decreased soil macroporosity and microbial biomass of carbon and nitrogen. Principal coordinates analyses confirmed different taxonomic and functional profiles for each treatment. There was predominance of the Bacteria domain, especially the phylum Proteobacteria, with higher numbers of sequences in the NT and CT treatments; Archaea and Viruses also had lower numbers of sequences in the undisturbed soil. Within the Alphaproteobacteria, there was dominance of Rhizobiales and of the genus Bradyrhizobium in the NT and CT systems, attributed to massive inoculation of soybean, and also of Burkholderiales. In contrast, Rhizobium, Azospirillum, Xanthomonas, Pseudomonas and Acidobacterium predominated in the native Cerrado. More Eukaryota, especially of the phylum Ascomycota were detected in the NT. The functional analysis revealed lower numbers of sequences in the five dominant categories for the CT system, whereas the undisturbed Cerrado presented higher abundance. High impact of agriculture in taxonomic and functional microbial diversity in the biome Cerrado was confirmed. Functional diversity was not necessarily associated with taxonomic diversity, as the less conservationist treatment (CT) presented increased taxonomic sequences and reduced functional profiles, indicating a strategy to try to maintain soil functioning by favoring taxa that are probably not the most efficient for some functions. Our results highlight that underneath the rustic appearance of the Cerrado vegetation there is a fragile soil microbial community.

Clinically Significant Symptom Reduction in Children with Attention-Deficit/Hyperactivity Disorder Treated with Micronutrients: An Open-Label Reversal Design Study

PubMed Central

Gordon, Heather A; Rucklidge, Julia J; Blampied, Neville M; Johnstone, Jeanette M

2015-01-01

Abstract Objective: The purpose of this study was to investigate the clinical effect and safety of a broad spectrum, 36 ingredient micronutrient (vitamins and minerals) in treating children with attention-deficit/hyperactivity disorder (ADHD). Methods: This open-label, on-off-on-off (reversal design) study followed 14 participants (8–12 years of age) with ADHD, diagnosed using standardized instruments, for 6 months with no dropouts. Following baseline assessment, including hematology and biochemistry screening, participants began an 8 week treatment phase with micronutrients titrated up to maximum dose (15 capsules/day). Treatment was withdrawn for 4 weeks, reinstated for a further 8 weeks, and then withdrawn for 4 weeks. Primary outcomes included the Conners' Parent Rating Scale, the Clinical Global Impressions Scale (CGI), and the Strengths and Difficulties Questionnaire – Parent version (SDQ). Secondary outcomes were mood and global functioning. Results: Modified Brinley plots revealed a reduction in ADHD symptoms, improved mood, and improved overall functioning during intervention phases, and deterioration in ADHD symptoms, mood, and overall functioning during the withdrawal phases. Reliable change analyses, Cohen's d and percent superiority effect sizes, 95% confidence intervals and t tests confirmed clinically and statistically significant change between the intervention and withdrawal phases, with large effect sizes observed pre- to post-exposure of micronutrients (d = 1.2–2.2) on ADHD symptoms during intervention phases. Seventy-one percent of participants showed at least a 30% decrease in ADHD symptoms by the end of the second treatment phase, and 79% were identified as “much improved” or “very much improved” at the end of the second phase (5 months) based on the clinician-rated CGI when considering functioning generally. The SDQ showed that these benefits occurred across other areas of functioning including emotional symptoms, conduct problems, and prosocial behaviours. The children's self-reports confirmed the improvements. Excellent adherence to treatment occurred throughout, side effects were mild and transitory, and no safety issues were identified through blood analyses. Conclusions: This study demonstrates the clinical benefit, feasibility, and safety of broad-spectrum micronutrients in the treatment of childhood ADHD. Replications utilizing double-blind placebo-controlled studies are warranted. Trial is registered with the Australia and New Zealand Clinical Trial Registry: ACTRN12612000645853 PMID:26682999

Coping and violence exposure as predictors of psychological functioning in domestic violence survivors.

PubMed

Lewis, Carla S; Griffing, Sascha; Chu, Melissa; Jospitre, Tania; Sage, Robert E; Madry, Lorraine; Primm, Beny J

2006-04-01

This study examines the differential effects of adult and childhood physical and psychological abuse, abuse-specific coping, and psychological adjustment in battered women seeking emergency shelter. Multivariate regression analyses confirmed the devastating impact of psychological abuse (childhood and concurrent) on battered women's adjustment. The results corroborated prior research suggesting a cumulative vulnerability to psychological victimization in a substantial proportion of residents. Unexpectedly, frequency of physical violence was unrelated to women's distress. The study argues that modes of coping traditionally considered adaptive (e.g., engaged, proactive) may be unsafe for battered women and children. The multifaceted nature of survivors' coping choices is discussed.

Application of higher harmonic blade feathering for helicopter vibration reduction

NASA Technical Reports Server (NTRS)

Powers, R. W.

1978-01-01

Higher harmonic blade feathering for helicopter vibration reduction is considered. Recent wind tunnel tests confirmed the effectiveness of higher harmonic control in reducing articulated rotor vibratory hub loads. Several predictive analyses developed in support of the NASA program were shown to be capable of calculating single harmonic control inputs required to minimize a single 4P hub response. In addition, a multiple-input, multiple-output harmonic control predictive analysis was developed. All techniques developed thus far obtain a solution by extracting empirical transfer functions from sampled data. Algorithm data sampling and processing requirements are minimal to encourage adaptive control system application of such techniques in a flight environment.

Surface Functionalization of Diamond Films by Photoreaction of Elemental Sulfur and Their Surface Properties

NASA Astrophysics Data System (ADS)

Nakamura, Takako; Ohana, Tsuguyori

2012-08-01

A useful method for direct sulfurization of diamond film surfaces by photoreaction of elemental sulfur was developed. The introduction of thiol groups onto the diamond films was confirmed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and scanning electron microscopy (SEM) analyses. The sulfur-modified diamond films attached to gold nanoparticles by self-assembly. The degrees of thiol group introduction and gold attachment were found to depend on photoirradiation time by monitoring by XPS. The gold-modified diamond film was observed to act as a surface-enhanced Raman scattering substrate for measurement of picric acid.

Gravitational form factors and decoupling in 2D

NASA Astrophysics Data System (ADS)

Ribeiro, Tiago G.; Shapiro, Ilya L.; Zanusso, Omar

2018-07-01

We calculate and analyse non-local gravitational form factors induced by quantum matter fields in curved two-dimensional space. The calculations are performed for scalars, spinors and massive vectors by means of the covariant heat kernel method up to the second order in the curvature and confirmed using Feynman diagrams. The analysis of the ultraviolet (UV) limit reveals a generalized "running" form of the Polyakov action for a nonminimal scalar field and the usual Polyakov action in the conformally invariant cases. In the infrared (IR) we establish the gravitational decoupling theorem, which can be seen directly from the form factors or from the physical beta function for fields of any spin.

Analysis of delamination related fracture processes in composites

NASA Technical Reports Server (NTRS)

Armanios, Erian A.

1992-01-01

An anisotropic thin walled closed section beam theory was developed based on an asymptotical analysis of the shell energy functional. The displacement field is not assumed a priori and emerges as a result of the analysis. In addition to the classical out-of-plane torsional warping, two new contributions are identified namely, axial strain and bending warping. A comparison of the derived governing equations confirms the theory developed by Reissner and Tsai. Also, explicit closed form expressions for the beam stiffness coefficients, the stress and displacement fields are provided. The predictions of the present theory were validated by comparison with finite element simulation, other closed form analyses and test data.

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

Delayed pituitary adenylate cyclase-activating polypeptide delivery after brain stroke improves functional recovery by inducing m2 microglia/macrophage polarization.

PubMed

Brifault, Coralie; Gras, Marjorie; Liot, Donovan; May, Victor; Vaudry, David; Wurtz, Olivier

2015-02-01

Until now, except thrombolysis, the therapeutical strategies targeting the acute phase of cerebral ischemia have been proven ineffective, and no approach is available to attenuate the delayed cell death mechanisms and the resulting functional deficits in the late phase. Then, we investigated whether a targeted and delayed delivery of pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide known to exert neuroprotective activities, may dampen delayed pathophysiological processes improving functional recovery. Three days after permanent focal ischemia, PACAP-producing stem cells were transplanted intracerebro ventricularly in nonimmunosuppressed mice. At 7 and 14 days post ischemia, the effects of this stem cell-based targeted delivery of PACAP on functional recovery, volume lesions, and inflammatory processes were analyzed. The delivery of PACAP in the vicinity of the infarct zone 3 days post stroke promotes fast, stable, and efficient functional recovery. This was correlated with a modulation of the postischemic inflammatory response. Transcriptomic and Ingenuity Pathway Analysis-based bioinformatic analyses identified several gene networks, functions, and key transcriptional factors, such as nuclear factor-κB, C/EBP-β, and Notch/RBP-J as PACAP's potential targets. Such PACAP-dependent immunomodulation was further confirmed by morphometric and phenotypic analyses of microglial cells showing increased number of Arginase-1(+) cells in mice treated with PACAP-expressing cells specifically, demonstrating the redirection of the microglial response toward a neuroprotective M2 phenotype. Our results demonstrated that immunomodulatory strategies capable of redirecting the microglial response toward a neuroprotective M2 phenotype in the late phase of brain ischemia could represent attractive options for stroke treatment in a new and unexploited therapeutical window. © 2014 American Heart Association, Inc.

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.

A UDP-glucosyltransferase functions in both acylphloroglucinol glucoside and anthocyanin biosynthesis in strawberry (Fragaria × ananassa).

PubMed

Song, Chuankui; Zhao, Shuai; Hong, Xiaotong; Liu, Jingyi; Schulenburg, Katja; Schwab, Wilfried

2016-03-01

Physiologically active acylphloroglucinol (APG) glucosides were recently found in strawberry (Fragaria sp.) fruit. Although the formation of the APG aglycones has been clarified, little is known about APG glycosylation in plants. In this study we functionally characterized ripening-related glucosyltransferase genes in Fragaria by comprehensive biochemical analyses of the encoded proteins and by a RNA interference (RNAi) approach in vivo. The allelic proteins UGT71K3a/b catalyzed the glucosylation of diverse hydroxycoumarins, naphthols and flavonoids as well as phloroglucinols, enzymatically synthesized APG aglycones and pelargonidin. Total enzymatic synthesis of APG glucosides was achieved by co-incubation of recombinant dual functional chalcone/valerophenone synthase and UGT71K3 proteins with essential coenzyme A esters and UDP-glucose. An APG glucoside was identified in strawberry fruit which has not yet been reported in other plants. Suppression of UGT71K3 activity in transient RNAi-silenced fruits led to a loss of pigmentation and a substantial decrease of the levels of various APG glucosides and an anthocyanin. Metabolite analyses of transgenic fruits confirmed UGT71K3 as a UDP-glucose:APG glucosyltransferase in planta. These results provide the foundation for the breeding of fruits with improved health benefits and for the biotechnological production of bioactive natural products. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Different CHD chromatin remodelers are required for expression of distinct gene sets and specific stages during development of Dictyostelium discoideum

PubMed Central

Platt, James L.; Rogers, Benjamin J.; Rogers, Kelley C.; Harwood, Adrian J.; Kimmel, Alan R.

2013-01-01

Control of chromatin structure is crucial for multicellular development and regulation of cell differentiation. The CHD (chromodomain-helicase-DNA binding) protein family is one of the major ATP-dependent, chromatin remodeling factors that regulate nucleosome positioning and access of transcription factors and RNA polymerase to the eukaryotic genome. There are three mammalian CHD subfamilies and their impaired functions are associated with several human diseases. Here, we identify three CHD orthologs (ChdA, ChdB and ChdC) in Dictyostelium discoideum. These CHDs are expressed throughout development, but with unique patterns. Null mutants lacking each CHD have distinct phenotypes that reflect their expression patterns and suggest functional specificity. Accordingly, using genome-wide (RNA-seq) transcriptome profiling for each null strain, we show that the different CHDs regulate distinct gene sets during both growth and development. ChdC is an apparent ortholog of the mammalian Class III CHD group that is associated with the human CHARGE syndrome, and GO analyses of aberrant gene expression in chdC nulls suggest defects in both cell-autonomous and non-autonomous signaling, which have been confirmed through analyses of chdC nulls developed in pure populations or with low levels of wild-type cells. This study provides novel insight into the broad function of CHDs in the regulation development and disease, through chromatin-mediated changes in directed gene expression. PMID:24301467

The influence of symptoms on quality of life among patients who have undergone oesophageal cancer surgery.

PubMed

Ha, Seo-In; Kim, Kyunghee; Kim, Ji-Su

2016-10-01

After oesophagectomy, anatomical changes and loss of function induce various symptoms that may affect quality of life (QoL) in oesophageal cancer patients. The purpose of this study was to identify the factors influencing QoL in Korean patients who have undergone oesophageal cancer surgery. This was a cross-sectional study of a convenience sample consisting of 120 surgery patients with oesophageal cancer. We used the EORTC QLQ-C30 and EORTC QLQ-OES18 to measure participants' oesophageal cancer-related symptoms and QoL. Multiple regression analyses were applied to analyse to the relationship between cancer-related symptoms and QoL. The average score of oesophageal cancer-related symptoms was 19.28 points, and the most common symptom was reflux. The mean score for global health status/QoL was 60.55. There were significant differences in the functional and symptom subscales according to financial burden, operation type (procedure), and treatment period. Dysphagia most affected global health status/QoL, and eating problems most affected the functional and symptom subscales. Dysphagia and eating problems were confirmed to be the most common symptoms affecting the QoL of patients who had undergone oesophageal cancer surgery. These results can be used to aid in the development of strategies to better manage symptoms in these patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional Evolution in Orthologous Cell-encoded RNA-dependent RNA Polymerases.

PubMed

Qian, Xinlei; Hamid, Fursham M; El Sahili, Abbas; Darwis, Dina Amallia; Wong, Yee Hwa; Bhushan, Shashi; Makeyev, Eugene V; Lescar, Julien

2016-04-22

Many eukaryotic organisms encode more than one RNA-dependent RNA polymerase (RdRP) that probably emerged as a result of gene duplication. Such RdRP paralogs often participate in distinct RNA silencing pathways and show characteristic repertoires of enzymatic activities in vitro However, to what extent members of individual paralogous groups can undergo functional changes during speciation remains an open question. We show that orthologs of QDE-1, an RdRP component of the quelling pathway in Neurospora crassa, have rapidly diverged in evolution at the amino acid sequence level. Analyses of purified QDE-1 polymerases from N. crassa (QDE-1(Ncr)) and related fungi, Thielavia terrestris (QDE-1(Tte)) and Myceliophthora thermophila (QDE-1(Mth)), show that all three enzymes can synthesize RNA, but the precise modes of their action differ considerably. Unlike their QDE-1(Ncr) counterpart favoring processive RNA synthesis, QDE-1(Tte) and QDE-1(Mth) produce predominantly short RNA copies via primer-independent initiation. Surprisingly, a 3.19 Å resolution crystal structure of QDE-1(Tte) reveals a quasisymmetric dimer similar to QDE-1(Ncr) Further electron microscopy analyses confirm that QDE-1(Tte) occurs as a dimer in solution and retains this status upon interaction with a template. We conclude that divergence of orthologous RdRPs can result in functional innovation while retaining overall protein fold and quaternary structure. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Functional Evolution in Orthologous Cell-encoded RNA-dependent RNA Polymerases*

PubMed Central

Qian, Xinlei; Hamid, Fursham M.; El Sahili, Abbas; Darwis, Dina Amallia; Wong, Yee Hwa; Bhushan, Shashi; Makeyev, Eugene V.; Lescar, Julien

2016-01-01

Many eukaryotic organisms encode more than one RNA-dependent RNA polymerase (RdRP) that probably emerged as a result of gene duplication. Such RdRP paralogs often participate in distinct RNA silencing pathways and show characteristic repertoires of enzymatic activities in vitro. However, to what extent members of individual paralogous groups can undergo functional changes during speciation remains an open question. We show that orthologs of QDE-1, an RdRP component of the quelling pathway in Neurospora crassa, have rapidly diverged in evolution at the amino acid sequence level. Analyses of purified QDE-1 polymerases from N. crassa (QDE-1Ncr) and related fungi, Thielavia terrestris (QDE-1Tte) and Myceliophthora thermophila (QDE-1Mth), show that all three enzymes can synthesize RNA, but the precise modes of their action differ considerably. Unlike their QDE-1Ncr counterpart favoring processive RNA synthesis, QDE-1Tte and QDE-1Mth produce predominantly short RNA copies via primer-independent initiation. Surprisingly, a 3.19 Å resolution crystal structure of QDE-1Tte reveals a quasisymmetric dimer similar to QDE-1Ncr. Further electron microscopy analyses confirm that QDE-1Tte occurs as a dimer in solution and retains this status upon interaction with a template. We conclude that divergence of orthologous RdRPs can result in functional innovation while retaining overall protein fold and quaternary structure. PMID:26907693

Microbial and functional diversity of a subterrestrial high pH groundwater associated to serpentinization.

PubMed

Tiago, Igor; Veríssimo, António

2013-06-01

Microbial and functional diversity were assessed, from a serpentinization-driven subterrestrial alkaline aquifer - Cabeço de Vide Aquifer (CVA) in Portugal. DGGE analyses revealed the presence of a stable microbial community. By 16S rRNA gene libraries and pyrosequencing analyses, a diverse bacterial composition was determined, contrasting with low archaeal diversity. Within Bacteria the majority of the populations were related to organisms or sequences affiliated to class Clostridia, but members of classes Acidobacteria, Actinobacteria, Alphaproteobacteria, Betaproteobacteria, Deinococci, Gammaproteobacteria and of the phyla Bacteroidetes, Chloroflexi and Nitrospira were also detected. Domain Archaea encompassed mainly sequences affiliated to Euryarchaeota. Only form I RuBisCO - cbbL was detected. Autotrophic carbon fixation via the rTCA, 3-HP and 3-HP/4H-B cycles could not be confirmed. The detected APS reductase alpha subunit - aprA sequences were phylogenetically related to sequences of sulfate-reducing bacteria belonging to Clostridia, and also to sequences of chemolithoautothrophic sulfur-oxidizing bacteria belonging to Betaproteobacteria. Sequences of methyl coenzyme M reductase - mcrA were phylogenetically affiliated to sequences belonging to Anaerobic Methanotroph group 1 (ANME-1). The populations found and the functional key markers detected in CVA suggest that metabolisms related to H2 , methane and/or sulfur may be the major driving forces in this environment. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Transgenic approach to improve wheat (Triticum aestivum L.) nutritional quality.

PubMed

Tamás, Cecília; Kisgyörgy, Boglárka N; Rakszegi, Mariann; Wilkinson, Mark D; Yang, Moon-Sik; Láng, László; Tamás, László; Bedo, Zoltán

2009-07-01

An amaranth (Amaranthus hypochondriacus) albumin gene, encoding the 35-kDa AmA1 protein of the seed, with a high content of essential amino acids, was used in the biolistic transformation of bread wheat (Triticum aestivum L.) variety Cadenza. The transformation cassette carried the ama1 gene under the control of a powerful wheat endosperm-specific promoter (1Bx17 HMW-GS). Southern-blot analysis of T(1) lines confirmed the integration of the foreign gene, while RT-PCR and Western-blot analyses of the samples confirmed the transcription and translation of the transgene. The effects of the extra albumin protein on the properties of flour, produced from bulked T(2) seeds, were calculated using total protein and essential amino acid content analysis, polymeric/monomeric protein and HMW/LMW glutenin subunit ratio measurements. The results indicated that not only can essential amino acid content be increased, but some parameters associated with functional quality may also be improved because of the expression of the AmA1 protein.

High spin state driven magnetism and thermoelectricity in Mn doped topological insulator Bi2Se3

NASA Astrophysics Data System (ADS)

Maurya, V. K.; Dong, C. L.; Chen, C. L.; Asokan, K.; Patnaik, S.

2018-06-01

We report on the synthesis, and structural - magnetic characterizations of Mn doped Bi2Se3 towards achieving a magnetically doped topological insulator. High quality single crystals of MnxBi2-xSe3 (x = 0, 0.03, 0.05, 0.1) are grown and analysed by X-ray diffraction (XRD), Low Energy Electron Diffraction (LEED), Scanning electron microscopy (SEM), and X-ray absorption near-edge structure spectroscopy (XANES). Magnetic properties of these samples under ZFC-FC protocol and isothermal magnetization confirm ferromagnetic correlation above x = 0.03 value. XANES measurements confirm that the dopant Mn is in Mn2+ state. This is further reconfirmed to be in high spin state by fitting magnetic data with Brillouin function for J = 5/2. Both Hall and Seebeck measurements indicate a sign change of charge carriers above x = 0.03 value of Mn doping. We propose Mn doped Bi2Se3 to be a potential candidate for electromagnetic and thermoelectric device applications involving topological surface states.

Optical, mechanical and thermal behaviors of Nitrilotriacetic acid single crystal

NASA Astrophysics Data System (ADS)

Deepa, B.; Philominathan, P.

2017-11-01

An organic nonlinear single crystal of Nitrilotriacetic acid (NTAA) was grown for the first time by employing a simple slow evaporation technique. Single crystal X-ray diffraction (XRD) analysis reveals that the grown crystal belongs to the monoclinic system with noncentrosymmetric space group CC. Fourier transform infrared (FTIR) spectral study ascertains the presence of functional groups in NTAA. The molecular structure of the grown crystal was confirmed by Nuclear Magnetic Resonance (NMR) spectral analysis. The optical parameters such as transmittance, absorption coefficient and band gap were calculated from UV-Visible and fluorescence studies. Dielectric measurements were carried out for different frequency and temperature. The mechanical strength of the grown crystal was measured using Vickers microhardness test. The high thermal stability and the melting point of the grown crystal were also estimated using thermogravimetric (TGA) and differential thermal analyses (DTA). The confirmation of the grown crystals belonging to nonlinear optical crystals was performed by Kurtz-Perry technique and found as suitable candidate for optoelectronics applications.

Poly(allyl methacrylate) functionalized hydroxyapatite nanocrystals via the combination of surface-initiated RAFT polymerization and thiol-ene protocol: a potential anticancer drug nanocarrier.

PubMed

Bach, Long Giang; Islam, Md Rafiqul; Vo, Thanh-Sang; Kim, Se-Kwon; Lim, Kwon Taek

2013-03-15

Hydroxyapatite nanocrystals (HAP NCs) were encapsulated by poly(allyl methacrylate) (PolyAMA) employing controlled surface-initiated reversible addition-fragmentation chain transfer (SI-RAFT) polymerization of allyl methacrylate to afford HAP-PolyAMA nanohybrids. The subsequent thiol-ene coupling of nanohybrids with 2-mercaptosuccinic acid resulted HAP-Poly(AMA-COOH) possessing multicarboxyl group. The formation of the nanohybrids was confirmed by FT-IR and EDS analyses. The TGA and FE-SEM investigation were further suggested the grafting of PolyAMA onto HAP NCs. The utility of the HAP-PolyAMA nanohybrid as drug carrier was also explored. The pendant carboxyl groups on the external layers of nanohybrids were conjugated with anticancer drug cisplatin to afford HAP-Poly(AMA-COOH)/Pt complex. The formation of the complex was confirmed by FT-IR, XPS, and FE-SEM. In vitro evaluation of the synthesized complex as nanomedicine revealed its potential chemotherapeutic efficacy against cancer cell lines. Copyright © 2012 Elsevier Inc. All rights reserved.

Optical, electrochemical and thermal properties of Mn2+ doped CdS nanoparticles

NASA Astrophysics Data System (ADS)

Muruganandam, S.; Anbalagan, G.; Murugadoss, G.

2015-08-01

Mn2+ doped (1-5 and 10 %) CdS nanoparticles have been synthesized by the chemical precipitation method using polyvinylpyrrolidone as a capping agent. The particle size, morphology and optical properties have been studied by X-ray powder diffraction, transmission electron microscopy, UV-Visible and photoluminescence spectroscopy. Powder diffraction data have confirmed that the crystallite size is around 2-5 nm. The band gap of the nanoparticles has been calculated using UV-Visible absorption spectra. An optimum concentration, Mn2+ (3 %) has been selected by optical study. The functional groups of the capping agent have been identified by fourier transform infrared spectroscopy study. The presence of dopant (Mn2+) has been confirmed by electron paramagnetic resonance spectroscopy. Thermal properties of CdS:Mn2+ have been analyzed using thermogravimetric-differential thermal analyser. The electrochemical properties of the undoped and doped samples have been studied by cyclic voltammetry for electrode applications. In addition, magnetic properties of Mn2+ doped CdS have been studied using a vibrating sample magnetometer.

Verification of presence of caprolactam in sprouted achenes of Fagopyrum esculentum Moench and its influence on plant phenolic compound content.

PubMed

Kalinová, Jana P; Tříska, Jan; Vrchotová, Naděžda; Moos, Martin

2014-08-15

The presence of caprolactam, a precursor of Nylon-6, among those synthetic polymers which are widely-spread throughout the environment, could be the reason for its being found in plants. The aim of this work was to confirm the previously described presence of caprolactam in dry and sprouted achenes, as well as in achene exudates of common buckwheat (Fagopyrum esculentum Moench). When the lyophilized sprouted and dry buckwheat achenes, along with exudates from growth experiments, with caprolactam-free medium were analysed by HPLC, no caprolactam was found. After addition of caprolactam into the growth medium, we confirmed the uptake of caprolactam in the lyophilized sprouted buckwheat achenes. The uptake of caprolactam is also a function of light conditions during the growth experiments. Caprolactam also inhibits the content of phenolic compounds; especially rutin, vitexin, isovitexin, orientin, and homoorientin in buckwheat plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

High density genetic mapping identifies new susceptibility loci for rheumatoid arthritis

PubMed Central

Eyre, Steve; Bowes, John; Diogo, Dorothée; Lee, Annette; Barton, Anne; Martin, Paul; Zhernakova, Alexandra; Stahl, Eli; Viatte, Sebastien; McAllister, Kate; Amos, Christopher I.; Padyukov, Leonid; Toes, Rene E.M.; Huizinga, Tom W.J.; Wijmenga, Cisca; Trynka, Gosia; Franke, Lude; Westra, Harm-Jan; Alfredsson, Lars; Hu, Xinli; Sandor, Cynthia; de Bakker, Paul I.W.; Davila, Sonia; Khor, Chiea Chuen; Heng, Khai Koon; Andrews, Robert; Edkins, Sarah; Hunt, Sarah E; Langford, Cordelia; Symmons, Deborah; Concannon, Pat; Onengut-Gumuscu, Suna; Rich, Stephen S; Deloukas, Panos; Gonzalez-Gay, Miguel A.; Rodriguez-Rodriguez, Luis; Ärlsetig, Lisbeth; Martin, Javier; Rantapää-Dahlqvist, Solbritt; Plenge, Robert; Raychaudhuri, Soumya; Klareskog, Lars; Gregersen, Peter K; Worthington, Jane

2012-01-01

Summary Using the Immunochip custom single nucleotide polymorphism (SNP) array, designed for dense genotyping of 186 genome wide association study (GWAS) confirmed loci we analysed 11,475 rheumatoid arthritis cases of European ancestry and 15,870 controls for 129,464 markers. The data were combined in meta-analysis with GWAS data from additional independent cases (n=2,363) and controls (n=17,872). We identified fourteen novel loci; nine were associated with rheumatoid arthritis overall and 5 specifically in anti-citrillunated peptide antibody positive disease, bringing the number of confirmed European ancestry rheumatoid arthritis loci to 46. We refined the peak of association to a single gene for 19 loci, identified secondary independent effects at six loci and association to low frequency variants (minor allele frequency <0.05) at 4 loci. Bioinformatic analysis of the data generated strong hypotheses for the causal SNP at seven loci. This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations. PMID:23143596

MULTISCALE ADAPTIVE SMOOTHING MODELS FOR THE HEMODYNAMIC RESPONSE FUNCTION IN FMRI*

PubMed Central

Wang, Jiaping; Zhu, Hongtu; Fan, Jianqing; Giovanello, Kelly; Lin, Weili

2012-01-01

In the event-related functional magnetic resonance imaging (fMRI) data analysis, there is an extensive interest in accurately and robustly estimating the hemodynamic response function (HRF) and its associated statistics (e.g., the magnitude and duration of the activation). Most methods to date are developed in the time domain and they have utilized almost exclusively the temporal information of fMRI data without accounting for the spatial information. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) in the frequency domain by integrating the spatial and temporal information to adaptively and accurately estimate HRFs pertaining to each stimulus sequence across all voxels in a three-dimensional (3D) volume. We use two sets of simulation studies and a real data set to examine the finite sample performance of MASM in estimating HRFs. Our real and simulated data analyses confirm that MASM outperforms several other state-of-art methods, such as the smooth finite impulse response (sFIR) model. PMID:24533041

Extended use of electronic health records by primary care physicians: Does the electronic health record artefact matter?

PubMed

Raymond, Louis; Paré, Guy; Marchand, Marie

2017-04-01

The deployment of electronic health record systems is deemed to play a decisive role in the transformations currently being implemented in primary care medical practices. This study aims to characterize electronic health record systems from the perspective of family physicians. To achieve this goal, we conducted a survey of physicians practising in private clinics located in Quebec, Canada. We used valid responses from 331 respondents who were found to be representative of the larger population. Data provided by the physicians using the top three electronic health record software products were analysed in order to obtain statistically adequate sub-sample sizes. Significant differences were observed among the three products with regard to their functional capability. The extent to which each of the electronic health record functionalities are used by physicians also varied significantly. Our results confirm that the electronic health record artefact 'does matter', its clinical functionalities explaining why certain physicians make more extended use of their system than others.

Clinical outcomes in cystic fibrosis patients with Trichosporon respiratory infection.

PubMed

Esther, Charles R; Plongla, Rongpong; Kerr, Alan; Lin, Feng-Chang; Gilligan, Peter

2016-09-01

Relationships between clinical outcomes and novel respiratory pathogens such as Trichosporon are not well understood. Respiratory cultures from CF patients were screened for novel pathogens Trichosporon and Chryseobacterium as well as other pathogens over 28months. Relationships between microbiologic and clinical data were assessed using univariate and multivariate methods. Of 4934 respiratory cultures from 474 CF patients, 37 cultures from 10 patients were Trichosporon positive. Patients with positive Trichosproron cultures had a greater decline in FEV1 over time (-3.9%/year vs. -1.3%/year, p<0.05), whereas Chryseobacterium did not influence lung function. These findings were confirmed in multivariate analyses that included age, gender, and other common pathogens as confounders. Treatment of Trichosporon infected patients was associated with improved lung function. Trichosporon can be recovered from a small but clinically meaningful fraction of CF patients. The presence of Trichosporon, but not Chryseobacterium, is associated with greater declines in lung function. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.).

PubMed

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming; Liu, Jingmei

2009-01-01

A 1.8 kb 5'-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from -986 to -959 and from -472 to -424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative beta-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were approximately 10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves.

Two negative cis-regulatory regions involved in fruit-specific promoter activity from watermelon (Citrullus vulgaris S.)

PubMed Central

Yin, Tao; Wu, Hanying; Zhang, Shanglong; Liu, Jingmei; Lu, Hongyu; Zhang, Lingxiao; Xu, Yong; Chen, Daming

2009-01-01

A 1.8 kb 5′-flanking region of the large subunit of ADP-glucose pyrophosphorylase, isolated from watermelon (Citrullus vulgaris S.), has fruit-specific promoter activity in transgenic tomato plants. Two negative regulatory regions, from –986 to –959 and from –472 to –424, were identified in this promoter region by fine deletion analyses. Removal of both regions led to constitutive expression in epidermal cells. Gain-of-function experiments showed that these two regions were sufficient to inhibit RFP (red fluorescent protein) expression in transformed epidermal cells when fused to the cauliflower mosaic virus (CaMV) 35S minimal promoter. Gel mobility shift experiments demonstrated the presence of leaf nuclear factors that interact with these two elements. A TCCAAAA motif was identified in these two regions, as well as one in the reverse orientation, which was confirmed to be a novel specific cis-element. A quantitative β-glucuronidase (GUS) activity assay of stable transgenic tomato plants showed that the activities of chimeric promoters harbouring only one of the two cis-elements, or both, were ∼10-fold higher in fruits than in leaves. These data confirm that the TCCAAAA motif functions as a fruit-specific element by inhibiting gene expression in leaves. PMID:19073962

Novel fMRI working memory paradigm accurately detects cognitive impairment in Multiple Sclerosis

PubMed Central

Nelson, Flavia; Akhtar, Mohammad A.; Zúñiga, Edward; Perez, Carlos A.; Hasan, Khader M.; Wilken, Jeffrey; Wolinsky, Jerry S.; Narayana, Ponnada A.; Steinberg, Joel L.

2016-01-01

Background Cognitive impairment (CI) cannot be diagnosed by MRI. Functional MRI (fMRI) paradigms such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory. Preliminary findings using I/DMT, showed differences in Blood Oxygenation Level Dependent (BOLD) activation between impaired (MSCI, n=12) and non-impaired (MSNI, n=9) MS patients. Objectives To confirm CI detection based on I/DMT’ BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and EDSS in magnitude of BOLD signal were also sought. Methods Fifty patients [EDSS mean (m) = 3.2, DD m =12 yr., age m =40yr.] underwent the Minimal Assessment of Cognitive Function in MS (MACFIMS) and the I/DMT. Working-memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. Results 10 MSNI, 30 MSCI and 4 borderline patients were included in analyses. ANOVA showed MSNI had significantly greater WMa than MSCI, in the left (L) prefrontal cortex and L supplementary motor area (p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas (p = 0.005, 0.004 respectively). Conclusion I/DMT-based BOLD activation detects CI in MS, larger studies are needed to confirm these findings. PMID:27613119

Establishment of the structural and enhanced physicochemical properties of the cocrystal-2-benzyl amino pyridine with oxalic acid

NASA Astrophysics Data System (ADS)

Sangeetha, M.; Mathammal, R.

2017-09-01

We report on a cocrystal of 2-(benzyl amino) pyridine (BAP) with oxalic acid (OA) in the ratio 1:1. The cocrystal was synthesised and single crystals were grown under slow evaporation technique at room temperature. Single crystal X-ray diffraction (SCXRD) analysis determined the structure of the cocrystal formed and it belongs to orthorhombic system with Cc space group. It was also subjected to X-ray Powder diffraction (XRPD) to confirm the cocrystal structure. Hirshfeld surfaces and fingerprints were plotted to analyze the intermolecular interactions. Spectroscopic techniques such as FTIR, FT-Raman and NMR were carried out to identify the functional groups present in the cocrystal. The bioactivity of the cocrystal was revealed from the UV-Vis analysis. Computational Density Functional Theory (DFT) was adopted at the B3LYP/6-31+G** level to calculate the optimized geometrical parameters and the vibrational frequencies of the cocrystal. The non-linear optical property of the cocrystal was revealed from the SHG test. The different types of interactions and delocalization of charge were analysed from Natural Bond Orbital (NBO) calculations. The HOMO-LUMO energies and MEP surface maps confirmed the pharmaceutical importance of the (1:1) BAPOA cocrystal. The cocrystal has been explored for the invitro antioxidant activity and insilico molecular docking studies.

Effectiveness of a novel integrative online treatment for depression (Deprexis): randomized controlled trial.

PubMed

Meyer, Björn; Berger, Thomas; Caspar, Franz; Beevers, Christopher G; Andersson, Gerhard; Weiss, Mario

2009-05-11

Depression is associated with immense suffering and costs, and many patients receive inadequate care, often because of the limited availability of treatment. Web-based treatments may play an increasingly important role in closing this gap between demand and supply. We developed the integrative, Web-based program Deprexis, which covers therapeutic approaches such as behavioral activation, cognitive restructuring, mindfulness/acceptance exercises, and social skills training. To evaluate the effectiveness of the Web-based intervention in a randomized controlled trial. There were 396 adults recruited via Internet depression forums in Germany, and they were randomly assigned in an 80:20 weighted randomization sequence to either 9 weeks of immediate-program-access as an add-on to treatment-as-usual (N = 320), or to a 9-week delayed-access plus treatment-as-usual condition (N = 76). At pre- and post-treatment and 6-month follow-up, we measured depression (Beck Depression Inventory) as the primary outcome measure and social functioning (Work and Social Adjustment Scale) as the secondary outcome measure. Complete analyses and intention-to-treat analyses were performed. Of 396 participants, 216 (55%) completed the post-measurement 9 weeks later. Available case analyses revealed a significant reduction in depression severity (BDI), Cohen's d = .64 (CI 95% = 0.33 - 0.94), and significant improvement in social functioning (WSA), Cohen's d = .64, 95% (CI 95% = 0.33 - 0.95). These improvements were maintained at 6-month follow-up. Intention-to-treat analyses confirmed significant effects on depression and social functioning improvements (BDI: Cohen's d = .30, CI 95% = 0.05 - 0.55; WSA: Cohen's d = .36, CI 95% = 0.10 - 0.61). Moreover, a much higher percentage of patients in the intervention group experienced a significant reduction of depression symptoms (BDI: odds ratio [OR] = 6.8, CI 95% = 2.90 - 18.19) and recovered more often (OR = 17.3, 95% CI 2.3 - 130). More than 80% of the users felt subjectively that the program had been helpful. This integrative, Web-based intervention was effective in reducing symptoms of depression and in improving social functioning. Findings suggest that the program could serve as an adjunctive or stand-alone treatment tool for patients suffering from symptoms of depression.

Proteomics in investigation of cancer metastasis: functional and clinical consequences and methodological challenges.

PubMed

Maryáš, Josef; Faktor, Jakub; Dvořáková, Monika; Struhárová, Iva; Grell, Peter; Bouchal, Pavel

2014-03-01

Metastases are responsible for most of the cases of death in patients with solid tumors. There is thus an urgent clinical need of better understanding the exact molecular mechanisms and finding novel therapeutics targets and biomarkers of metastatic disease of various tumors. Metastases are formed in a complicated biological process called metastatic cascade. Up to now, proteomics has enabled the identification of number of metastasis-associated proteins and potential biomarkers in cancer tissues, microdissected cells, model systems, and secretomes. Expression profiles and biological role of key proteins were confirmed in verification and functional experiments. This communication reviews these observations and analyses the methodological aspects of the proteomics approaches used. Moreover, it reviews contribution of current proteomics in the field of functional characterization and interactome analysis of proteins involved in various events in metastatic cascade. It is evident that ongoing technical progress will further increase proteome coverage and sample capacity of proteomics technologies, giving complex answers to clinical and functional questions asked. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Executive functioning as a mediator of the relationship between premorbid verbal intelligence and health risk behaviors in a rural-dwelling cohort: a Project FRONTIER study.

PubMed

Menon, Chloe V; Jahn, Danielle R; Mauer, Cortney B; O'Bryant, Sid E

2013-03-01

Limited research is available regarding the impact of neuropsychological functioning on health risk behaviors in rural-dwelling elderly populations. This cross-sectional study examined the relationships between estimated premorbid verbal IQ (AMNART), executive functioning impairment (EXIT25), and health risk behaviors including alcohol use (AUDIT), smoking, compliance with recommended cancer screenings, and obesity (BMI). The total sample included 456 English-speaking adults and older adults of non-Hispanic White and Hispanic origin seen as part of an ongoing study of rural cognitive aging, Project FRONTIER. Regression analyses revealed significant independent effects of AMNART and EXIT25 on most health risk behaviors, and supported the hypothesized mediating role of EXIT25 on the relationships between AMNART and smoking, cancer screenings, and BMI in both cognitively impaired and healthy subgroups. This study clarifies the relationships between executive functioning, premorbid IQ, and health risk behaviors in diverse groups, and confirms that premorbid IQ represents an important determinant of health behaviors and neurocognitive outcomes.

In-frame Val216-Ser217 deletion of KIT in mild piebaldism causes aberrant secretion and SCF response.

PubMed

Hattori, Mai; Ishikawa, Osamu; Oikawa, Daisuke; Amano, Hiroo; Yasuda, Masahito; Kaira, Kyoichi; Ishida-Yamamoto, Akemi; Nakano, Hajime; Sawamura, Daisuke; Terawaki, Shin-Ichi; Wakamatsu, Kaori; Tokunaga, Fuminori; Shimizu, Akira

2018-03-21

Piebaldism is a pigmentary disorder characterized by a white forelock and depigmented patches. Although the loss-of-function mutations in the KIT gene underlie the disease, the intracellular dynamics of the mutant KIT are largely unknown. We herein report a Japanese family with piebaldism in which the affected members showed a mild phenotype. The objective of this study is to investigate the functions and intracellular dynamics of the mutant KIT protein. We performed genetic analyses of the KIT gene using peripheral blood cells. We analyzed the intracellular localization of the mutant KIT protein in HEK293T cells transfected with wild-type (Wt) and/or mutant KIT genes. Immunoprecipitation analyses, immunoblotting and immunofluorescence studies were performed using antibodies against KIT and downstream signaling proteins. Glycosidase digestion analysis was performed to clarify the intracellular localization of KIT protein. A genetic analysis revealed a novel heterozygous mutation c.645_650delTGTGTC which results in the in-frame deletion of Val 216 and Ser 217 in the extracellular domain of KIT. Immunoprecipitation analyses confirmed that the wild and mutant KIT formed a heterodimer after treatment with stem cell factor (SCF); however, the phosphorylation of the downstream signaling factors was decreased. In an immunofluorescence study, the mutant KIT accumulated predominantly in the endoplasmic reticulum (ER) and was sparsely expressed on the cell surface. A glycosidase digestion study revealed that the mutant KIT is predominantly localized in the ER. These data reveal an aberrant function and intracellular localization of mutant KIT protein in piebaldism. Copyright © 2018 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. 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 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

Functional redundancy and/or ongoing pseudogenization among F-box protein genes expressed in Arabidopsis male gametophyte.

PubMed

Ikram, Sobia; Durandet, Monique; Vesa, Simona; Pereira, Serge; Guerche, Philippe; Bonhomme, Sandrine

2014-06-01

F-box protein genes family is one of the largest gene families in plants, with almost 700 predicted genes in the model plant Arabidopsis. F-box proteins are key components of the ubiquitin proteasome system that allows targeted protein degradation. Transcriptome analyses indicate that half of these F-box protein genes are found expressed in microspore and/or pollen, i.e., during male gametogenesis. To assess the role of F-box protein genes during this crucial developmental step, we selected 34 F-box protein genes recorded as highly and specifically expressed in pollen and isolated corresponding insertion mutants. We checked the expression level of each selected gene by RT-PCR and confirmed pollen expression for 25 genes, but specific expression for only 10 of the 34 F-box protein genes. In addition, we tested the expression level of selected F-box protein genes in 24 mutant lines and showed that 11 of them were null mutants. Transmission analysis of the mutations to the progeny showed that none of the single mutations was gametophytic lethal. These unaffected transmission efficiencies suggested leaky mutations or functional redundancy among F-box protein genes. Cytological observation of the gametophytes in the mutants confirmed these results. Combinations of mutations in F-box protein genes from the same subfamily did not lead to transmission defect either, further highlighting functional redundancy and/or a high proportion of pseudogenes among these F-box protein genes.

Whole genome sequence analyses of brain imaging measures in the Framingham Study.

PubMed

Sarnowski, Chloé; Satizabal, Claudia L; DeCarli, Charles; Pitsillides, Achilleas N; Cupples, L Adrienne; Vasan, Ramachandran S; Wilson, James G; Bis, Joshua C; Fornage, Myriam; Beiser, Alexa S; DeStefano, Anita L; Dupuis, Josée; Seshadri, Sudha

2018-01-16

We sought to identify rare variants influencing brain imaging phenotypes in the Framingham Heart Study by performing whole genome sequence association analyses within the Trans-Omics for Precision Medicine Program. We performed association analyses of cerebral and hippocampal volumes and white matter hyperintensity (WMH) in up to 2,180 individuals by testing the association of rank-normalized residuals from mixed-effect linear regression models adjusted for sex, age, and total intracranial volume with individual variants while accounting for familial relatedness. We conducted gene-based tests for rare variants using (1) a sliding-window approach, (2) a selection of functional exonic variants, or (3) all variants. We detected new loci in 1p21 for cerebral volume (minor allele frequency [MAF] 0.005, p = 10 -8 ) and in 16q23 for hippocampal volume (MAF 0.05, p = 2.7 × 10 -8 ). Previously identified associations in 12q24 for hippocampal volume (rs7294919, p = 4.4 × 10 -4 ) and in 17q25 for WMH (rs7214628, p = 2.0 × 10 -3 ) were confirmed. Gene-based tests detected associations ( p ≤ 2.3 × 10 -6 ) in new loci for cerebral (5q13, 8p12, 9q31, 13q12-q13, 15q24, 17q12, 19q13) and hippocampal volumes (2p12) and WMH (3q13, 4p15) including Alzheimer disease- ( UNC5D ) and Parkinson disease-associated genes ( GBA ). Pathway analyses evidenced enrichment of associated genes in immunity, inflammation, and Alzheimer disease and Parkinson disease pathways. Whole genome sequence-wide search reveals intriguing new loci associated with brain measures. Replication of novel loci is needed to confirm these findings. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Mesoscale Thermodynamic Analysis of Atomic-Scale Dislocation-Obstacle Interactions Simulated by Molecular Dynamics

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

Monet, Giath; Bacon, David J; Osetskiy, Yury N

2010-01-01

Given the time and length scales in molecular dynamics (MD) simulations of dislocation-defect interactions, quantitative MD results cannot be used directly in larger scale simulations or compared directly with experiment. A method to extract fundamental quantities from MD simulations is proposed here. The first quantity is a critical stress defined to characterise the obstacle resistance. This mesoscopic parameter, rather than the obstacle 'strength' designed for a point obstacle, is to be used for an obstacle of finite size. At finite temperature, our analyses of MD simulations allow the activation energy to be determined as a function of temperature. The resultsmore » confirm the proportionality between activation energy and temperature that is frequently observed by experiment. By coupling the data for the activation energy and the critical stress as functions of temperature, we show how the activation energy can be deduced at a given value of the critical stress.« less

Vibrational algorithms for quantitative crystallographic analyses of hydroxyapatite-based biomaterials: I, theoretical foundations.

PubMed

Pezzotti, Giuseppe; Zhu, Wenliang; Boffelli, Marco; Adachi, Tetsuya; Ichioka, Hiroaki; Yamamoto, Toshiro; Marunaka, Yoshinori; Kanamura, Narisato

2015-05-01

The Raman spectroscopic method has quantitatively been applied to the analysis of local crystallographic orientation in both single-crystal hydroxyapatite and human teeth. Raman selection rules for all the vibrational modes of the hexagonal structure were expanded into explicit functions of Euler angles in space and six Raman tensor elements (RTE). A theoretical treatment has also been put forward according to the orientation distribution function (ODF) formalism, which allows one to resolve the statistical orientation patterns of the nm-sized hydroxyapatite crystallite comprised in the Raman microprobe. Close-form solutions could be obtained for the Euler angles and their statistical distributions resolved with respect to the direction of the average texture axis. Polarized Raman spectra from single-crystalline hydroxyapatite and textured polycrystalline (teeth enamel) samples were compared, and a validation of the proposed Raman method could be obtained through confirming the agreement between RTE values obtained from different samples.

Inhibition of Monometalated Methionine Aminopeptidase: Inhibitor Discovery and Crystallographic Analysis†

PubMed Central

Huang, Min; Xie, Sheng-Xue; Ma, Ze-Qiang; Huang, Qing-Qing; Nan, Fa-Jun; Ye, Qi-Zhuang

2008-01-01

Two divalent metal ions are commonly seen in the active site cavity of methionine aminopeptidase, and at least one of the metal ions is directly involved in catalysis. Although ample structural and functional information is available for dimetalated enzyme, methionine aminopeptidase likely functions as a monometalated enzyme under physiological conditions. Information on structure, as well as catalysis and inhibition, of the monometalated enzyme is lacking. By improving conditions of high throughput screening, we identified a unique inhibitor with specificity toward the monometalated enzyme. Kinetic characterization indicates a mutual exclusivity in binding between the inhibitor and the second metal ion at the active site. This is confirmed by X-ray structure, and this inhibitor coordinates with the first metal ion and occupies the space normally occupied by the second metal ion. Kinetic and structural analyses of the inhibition by this and other inhibitors provide insight in designing effective inhibitors of methionine aminopeptidase. PMID:17948983

Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants?

PubMed

Sancak, Selim; Gokmen Yildirim, Tulin; Topcuoglu, Sevilay; Yavuz, Taner; Karatekin, Guner; Ovali, Fahri

2016-01-01

To compare the efficacy of oral and intravenous paracetamol for closure of hemodynamically significant patent ductus arteriosus (HSPDA) in very low birth weight (VLBW) preterm infants. Eighteen VLBW infants with HSPDA treated with either intravenous (n = 10) or oral (n = 8) paracetamol at 60 mg/kg/d for three consecutive days were analysed retrospectively. Ductal closure rate and evaluation of liver function tests were the major outcomes. After two courses of treatment, HSPDA closure rate was higher in oral paracetamol group than that in the intravenous paracetamol group (88% versus 70%), but it was not statistically significant (p = 0.588). Liver function tests were normal after the treatment. Although it was not statistically significant, the cumulative closure rates were higher in oral paracetamol group than those in the intravenous group. Larger trials are needed to confirm these data.

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.

Ballistic aggregation in systems of inelastic particles: Cluster growth, structure, and aging

NASA Astrophysics Data System (ADS)

Paul, Subhajit; Das, Subir K.

2017-07-01

We study far-from-equilibrium dynamics in models of freely cooling granular gas and ballistically aggregating compact clusters. For both the cases, from event-driven molecular dynamics simulations, we have presented detailed results on structure and dynamics in space dimensions d =1 and 2. Via appropriate analyses it has been confirmed that the ballistic aggregation mechanism applies in d =1 granular gases as well. Aging phenomena for this mechanism, in both the dimensions, have been studied via the two-time density autocorrelation function. This quantity is demonstrated to exhibit scaling property similar to that in the standard phase transition kinetics. The corresponding functional forms have been quantified and the outcomes have been discussed in connection with the structural properties. Our results on aging establish a more complete equivalence between the granular gas and the ballistic aggregation models in d =1 .

Global analysis of the rat and human platelet proteome – the molecular blueprint for illustrating multi-functional platelets and cross-species function evolution

PubMed Central

Yu, Yanbao; Leng, Taohua; Yun, Dong; Liu, Na; Yao, Jun; Dai, Ying; Yang, Pengyuan; Chen, Xian

2013-01-01

Emerging evidences indicate that blood platelets function in multiple biological processes including immune response, bone metastasis and liver regeneration in addition to their known roles in hemostasis and thrombosis. Global elucidation of platelet proteome will provide the molecular base of these platelet functions. Here, we set up a high throughput platform for maximum exploration of the rat/human platelet proteome using integrated proteomics technologies, and then applied to identify the largest number of the proteins expressed in both rat and human platelets. After stringent statistical filtration, a total of 837 unique proteins matched with at least two unique peptides were precisely identified, making it the first comprehensive protein database so far for rat platelets. Meanwhile, quantitative analyses of the thrombin-stimulated platelets offered great insights into the biological functions of platelet proteins and therefore confirmed our global profiling data. A comparative proteomic analysis between rat and human platelets was also conducted, which revealed not only a significant similarity, but also an across-species evolutionary link that the orthologous proteins representing ‘core proteome’, and the ‘evolutionary proteome’ is actually a relatively static proteome. PMID:20443191

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

Metatranscriptomic analysis of diverse microbial communities reveals core metabolic pathways and microbiome-specific functionality.

PubMed

Jiang, Yue; Xiong, Xuejian; Danska, Jayne; Parkinson, John

2016-01-12

Metatranscriptomics is emerging as a powerful technology for the functional characterization of complex microbial communities (microbiomes). Use of unbiased RNA-sequencing can reveal both the taxonomic composition and active biochemical functions of a complex microbial community. However, the lack of established reference genomes, computational tools and pipelines make analysis and interpretation of these datasets challenging. Systematic studies that compare data across microbiomes are needed to demonstrate the ability of such pipelines to deliver biologically meaningful insights on microbiome function. Here, we apply a standardized analytical pipeline to perform a comparative analysis of metatranscriptomic data from diverse microbial communities derived from mouse large intestine, cow rumen, kimchi culture, deep-sea thermal vent and permafrost. Sequence similarity searches allowed annotation of 19 to 76% of putative messenger RNA (mRNA) reads, with the highest frequency in the kimchi dataset due to its relatively low complexity and availability of closely related reference genomes. Metatranscriptomic datasets exhibited distinct taxonomic and functional signatures. From a metabolic perspective, we identified a common core of enzymes involved in amino acid, energy and nucleotide metabolism and also identified microbiome-specific pathways such as phosphonate metabolism (deep sea) and glycan degradation pathways (cow rumen). Integrating taxonomic and functional annotations within a novel visualization framework revealed the contribution of different taxa to metabolic pathways, allowing the identification of taxa that contribute unique functions. The application of a single, standard pipeline confirms that the rich taxonomic and functional diversity observed across microbiomes is not simply an artefact of different analysis pipelines but instead reflects distinct environmental influences. At the same time, our findings show how microbiome complexity and availability of reference genomes can impact comprehensive annotation of metatranscriptomes. Consequently, beyond the application of standardized pipelines, additional caution must be taken when interpreting their output and performing downstream, microbiome-specific, analyses. The pipeline used in these analyses along with a tutorial has been made freely available for download from our project website: http://www.compsysbio.org/microbiome .

The mediating effect of psychological distress on functional dependence in stroke patients.

PubMed

Huang, Hui-Chuan; Huang, Li-Kai; Hu, Chaur-Jong; Chang, Chien-Hung; Lee, Hsin-Chien; Chi, Nai-Fang; Shyu, Meei-Ling; Chang, Hsiu-Ju

2014-12-01

To explore varied forms of psychological distress and to determine the mediating influence of psychological distress on functional outcomes in stroke patients. Previous studies attest to the influence of depression on poststroke functional recovery. While there is evidence for neuropathological deficits that occur after stroke to be associated with psychological distress, few studies have explored the effect of various types of psychological distress on functional recovery. A cross-sectional study was used. Data were collected from 178 first-time stroke patients. Study variables included demographic and disease characteristics (stroke location and stroke syndrome classification), psychological distress (the Chinese language version of the Emotional and Social Dysfunction Questionnaire) and functional outcome (Barthel index). Regression and mediation models were used to evaluate the effect of psychological distress on functional outcome. Results revealed that stroke patients experience various forms of mild psychological distress, including anger, helplessness, emotional dyscontrol, indifference, inertia and euphoria, after stroke. Regression and mediation analyses further confirmed that various forms of psychological distress significantly mediated the effect of severe stroke syndromes on functional dependence. The various forms of psychological distress after stroke might play a mediating role in functional recovery and explain how stroke severity affects functional dependence. By understanding the nature of various forms of psychological distress, healthcare professionals should adopt appropriate assessment instruments and design effective interventions to help improve mental and physical function of stroke patients. © 2014 John Wiley & Sons Ltd.

Comprehensive analysis of alternative splicing and functionality in neuronal differentiation of P19 cells.

PubMed

Suzuki, Hitoshi; Osaki, Ken; Sano, Kaori; Alam, A H M Khurshid; Nakamura, Yuichiro; Ishigaki, Yasuhito; Kawahara, Kozo; Tsukahara, Toshifumi

2011-02-18

Alternative splicing, which produces multiple mRNAs from a single gene, occurs in most human genes and contributes to protein diversity. Many alternative isoforms are expressed in a spatio-temporal manner, and function in diverse processes, including in the neural system. The purpose of the present study was to comprehensively investigate neural-splicing using P19 cells. GeneChip Exon Array analysis was performed using total RNAs purified from cells during neuronal cell differentiation. To efficiently and readily extract the alternative exon candidates, 9 filtering conditions were prepared, yielding 262 candidate exons (236 genes). Semiquantitative RT-PCR results in 30 randomly selected candidates suggested that 87% of the candidates were differentially alternatively spliced in neuronal cells compared to undifferentiated cells. Gene ontology and pathway analyses suggested that many of the candidate genes were associated with neural events. Together with 66 genes whose functions in neural cells or organs were reported previously, 47 candidate genes were found to be linked to 189 events in the gene-level profile of neural differentiation. By text-mining for the alternative isoform, distinct functions of the isoforms of 9 candidate genes indicated by the result of Exon Array were confirmed. Alternative exons were successfully extracted. Results from the informatics analyses suggested that neural events were primarily governed by genes whose expression was increased and whose transcripts were differentially alternatively spliced in the neuronal cells. In addition to known functions in neural cells or organs, the uninvestigated alternative splicing events of 11 genes among 47 candidate genes suggested that cell cycle events are also potentially important. These genes may help researchers to differentiate the roles of alternative splicing in cell differentiation and cell proliferation.

The Use of Asymptotic Functions for Determining Empirical Values of CN Parameter in Selected Catchments of Variable Land Cover

NASA Astrophysics Data System (ADS)

Wałęga, Andrzej; Młyński, Dariusz; Wachulec, Katarzyna

2017-12-01

The aim of the study was to assess the applicability of asymptotic functions for determining the value of CN parameter as a function of precipitation depth in mountain and upland catchments. The analyses were carried out in two catchments: the Rudawa, left tributary of the Vistula, and the Kamienica, right tributary of the Dunajec. The input material included data on precipitation and flows for a multi-year period 1980-2012, obtained from IMGW PIB in Warsaw. Two models were used to determine empirical values of CNobs parameter as a function of precipitation depth: standard Hawkins model and 2-CN model allowing for a heterogeneous nature of a catchment area. The study analyses confirmed that asymptotic functions properly described P-CNobs relationship for the entire range of precipitation variability. In the case of high rainfalls, CNobs remained above or below the commonly accepted average antecedent moisture conditions AMCII. The study calculations indicated that the runoff amount calculated according to the original SCS-CN method might be underestimated, and this could adversely affect the values of design flows required for the design of hydraulic engineering projects. In catchments with heterogeneous land cover, the results of CNobs were more accurate when 2-CN model was used instead of the standard Hawkins model. 2-CN model is more precise in accounting for differences in runoff formation depending on retention capacity of the substrate. It was also demonstrated that the commonly accepted initial abstraction coefficient λ = 0.20 yielded too big initial loss of precipitation in the analyzed catchments and, therefore, the computed direct runoff was underestimated. The best results were obtained for λ = 0.05.

Risk for femoral fractures in Parkinson's disease patients with and without severe functional impairment.

PubMed

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Impaired balance is a major problem in patients with idiopathic Parkinson's disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28-2.98) than in women (HR = 1.79; 95%-CI: 1.66-1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment.

Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level.

PubMed

Wermter, Anne-Kathrin; Kamp-Becker, Inge; Hesse, Philipp; Schulte-Körne, Gerd; Strauch, Konstantin; Remschmidt, Helmut

2010-03-05

An increasing number of animal studies advert to a substantial role of the neuropeptide oxytocin in the regulation of social attachment and affiliation. Furthermore, animal studies showed anxiety and stress-reduced effects of oxytocin. First human studies confirm these findings in animal studies and implicate a crucial role of oxytocin in human social attachment behavior and in social interactions. Thus, the oxytocin system might be involved in the impairment of social interaction and attachment in autism spectrum disorders (ASD). The human oxytocin receptor gene (OXTR) represents a plausible candidate gene for the etiology of ASD. To analyze whether genetic variants in the OXTR gene are associated with ASD we performed family-based single-marker and haplotype association analyses with 22 single nucleotide polymorphisms (SNPs) in the OXTR and its 5' region in 100 families with autistic disorders on high-functioning level (Asperger syndrome (AS), high-functioning autism (HFA), and atypical autism (AA)). Single-marker and haplotype association analyses revealed nominally significant associations of one single SNP and one haplotype with autism, respectively. Furthermore, employing a "reverse phenotyping" approach, patients carrying the haplotype associated with autism showed nominally significant impairments in comparison to noncarriers of the haplotype in items of the Autism Diagnostic Interview-Revised algorithm describing aspects of social interaction and communication. In conclusion, our results implicate that genetic variation in the OXTR gene might be relevant in the etiology of autism on high-functioning level. (c) 2009 Wiley-Liss, Inc.

Controlled comparison of family cognitive behavioral therapy and psychoeducation/relaxation training for child obsessive-compulsive disorder.

PubMed

Piacentini, John; Bergman, R Lindsey; Chang, Susanna; Langley, Audra; Peris, Tara; Wood, Jeffrey J; McCracken, James

2011-11-01

To examine the efficacy of exposure-based cognitive-behavioral therapy (CBT) plus a structured family intervention (FCBT) versus psychoeducation plus relaxation training (PRT) for reducing symptom severity, functional impairment, and family accommodation in youths with obsessive-compulsive disorder (OCD). A total of 71 youngsters 8 to 17 years of age (mean 12.2 years; range, 8-17 years, 37% male, 78% Caucasian) with primary OCD were randomized (70:30) to 12 sessions over 14 weeks of FCBT or PRT. Blind raters assessed outcomes with responders followed for 6 months to assess treatment durability. FCBT led to significantly higher response rates than PRT in ITT (57.1% vs 27.3%) and completer analyses (68.3% vs. 35.3%). Using HLM, FCBT was associated with significantly greater change in OCD severity and child-reported functional impairment than PRT and marginally greater change in parent-reported accommodation of symptoms. These findings were confirmed in some, but not all, secondary analyses. Clinical remission rates were 42.5% for FCBT versus 17.6% for PRT. Reduction in family accommodation temporally preceded improvement in OCD for both groups and child functional status for FCBT only. Treatment gains were maintained at 6 months. FCBT is effective for reducing OCD severity and impairment. Importantly, treatment also reduced parent-reported involvement in symptoms with reduced accommodation preceding reduced symptom severity and functional impairment. CLINICAL TRIALS REGISTRY INFORMATION: Behavior Therapy for Children and Adolescents with Obsessive-Compulsive Disorder (OCD); http://www.clinicaltrials.gov; NCT00000386. Copyright © 2011 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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.

Synthesis, growth, structural and optical studies of a novel organic Piperazine (bis) p-toluenesulfonate single crystal.

PubMed

Rekha, P; Peramaiyan, G; NizamMohideen, M; Kumar, R Mohan; Kanagadurai, R

2015-03-15

A novel organic single crystal of Piperazinium (bis) p-toluenesulfonate (PPTS) was grown by a slow evaporation solution growth technique. The structure of the grown crystal was determined using single crystal X-ray diffraction analysis. The PPTS crystal belongs to the triclinic crystal system with space group of P1¯. The presence of functional groups was confirmed by FTIR spectral analysis. The optical transmittance range and cut-off wavelength were identified by UV-vis-NIR spectral studies. The luminescent properties of PPTS crystal were investigated. The thermal behavior of PPTS crystal was studied by TG-DT analyses. Copyright © 2014 Elsevier B.V. All rights reserved.

Comorbid Depressive and Anxiety Disorders in 509 Individuals With an At-Risk Mental State: Impact on Psychopathology and Transition to Psychosis

PubMed Central

Fusar-Poli, Paolo

2014-01-01

Background: The current diagnostic system for subjects at enhanced clinical risk of psychosis allows concurrent comorbid diagnoses of anxiety and depressive disorders. Their impact on the presenting high-risk psychopathology, functioning, and transition outcomes has not been widely researched. Methods: In a large sample of subjects with an At-Risk Mental State (ARMS, n = 509), we estimated the prevalence of DSM/SCID anxiety or depressive disorders and their impact on psychopathology, functioning, and psychosis transition. A meta-analytical review of the literature complemented the analysis. Results: About 73% of ARMS subjects had a comorbid axis I diagnosis in addition to the “at-risk” signs and symptoms. About 40% of ARMS subjects had a comorbid diagnosis of depressive disorder while anxiety disorders were less frequent (8%). The meta-analysis conducted in 1683 high-risk subjects confirmed that baseline prevalence of comorbid depressive and anxiety disorders is respectively 41% and 15%. At a psychopathological level, comorbid diagnoses of anxiety or depression were associated with higher suicidality or self-harm behaviors, disorganized/odd/stigmatizing behavior, and avolition/apathy. Comorbid anxiety and depressive diagnoses were also associated with impaired global functioning but had no effect on risk of transition to frank psychosis. Meta-regression analyses confirmed no effect of baseline anxiety and/or depressive comorbid diagnoses on transition to psychosis. Conclusions: The ARMS patients are characterized by high prevalence of anxiety and depressive disorders in addition to their attenuated psychotic symptoms. These symptoms may reflect core emotional dysregulation processes and delusional mood in prodromal psychosis. Anxiety and depressive symptoms are likely to impact the ongoing psychopathology, the global functioning, and the overall longitudinal outcome of these patients. PMID:23180756

Changes in Soil Carbon Storage After Cultivation

DOE Data Explorer

Mann, L. K. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2004-01-01

Previously published data from 625 paired soil samples were used to predict carbon in cultivated soil as a function of initial carbon content. A 30-cm sampling depth provided a less variable estimate (r² = 0.9) of changes in carbon than a 15-cm sampling depth (r² = 0.6). Regression analyses of changes in carbon storage in relation to years of cultivation confirmed that the greatest rates of change occurred in the first 20 y. An initial carbon effect was present in all analyses: soils very low in carbon tended to gain slight amounts of carbon after cultivation, but soils high in carbon lost at least 20% during cultivation. Carbon losses from most agricultural soils are estimated to average less than 20% of initial values or less than 1.5 kg/m² within the top 30 cm. These estimates should not be applied to depths greater than 30 cm and would be improved with more bulk density information and equivalent sample volumes.

Immune changes during short-duration missions

NASA Technical Reports Server (NTRS)

Taylor, G. R.

1993-01-01

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Immune changes during short-duration missions.

PubMed

Taylor, G R

1993-09-01

Spaceflight materially influences the immune mechanism of humans and animals. Effects resulting from missions of less than 1 month are examined. Effects from longer missions are discussed in the companion paper by Konstantinova et al. Most immunology studies have involved analyses of subjects and samples from subjects obtained after flight, with the data being compared with similar data obtained before flight. These studies have demonstrated that short-duration missions can result in a postflight depression in blast cell transformation, major changes in cytokine function, and alterations in the relative numbers of immune cell populations. In addition to these post- vs. preflight studies, some data have been produced in flight. However, these in vitro analyses have been less than satisfactory because of differences between in-flight and ground-control conditions. Recently, both the U.S. and Russian space programs have started collecting in-flight, in vivo, cell-mediated immunity data. These studies have confirmed that the human cell-mediated immune system is blunted during spaceflight.

Synthesis, structural, optical, thermal and dielectric studies on new organic nonlinear optical crystal by solution growth technique.

PubMed

Prakash, M; Geetha, D; Lydia Caroline, M

2013-04-15

Single crystals of L-phenylalanine-benzoic acid (LPBA) were successfully grown from aqueous solution by solvent evaporation technique. Purity of the crystals was increased by the method of recrystallization. The XRD analysis confirms that the crystal belongs to the monoclinic system with noncentrosymmetric space group P21. The chemical structure of compound was established by FT-NMR technique. The presence of functional groups was estimated qualitatively by Fourier transform infrared analysis (FT-IR). Ultraviolet-visible spectral analyses showed that the crystal has low UV cut-off at 254 nm combined with very good transparency of 90% in a wide range. The optical band gap was estimated to be 6.91 eV. Thermal behavior has been studied with TGA/DTA analyses. The existence of second harmonic generation (SHG) efficiency was found to be 0.56 times the value of KDP. The dielectric behavior of the sample was also studied for the first time. Copyright © 2013 Elsevier B.V. All rights reserved.

Studies on synthesis, growth, structural, thermal, linear and nonlinear optical properties of organic picolinium maleate single crystals.

PubMed

Pandi, P; Peramaiyan, G; Sudhahar, S; Chakkaravarthi, G; Mohan Kumar, R; Bhagavannarayana, G; Jayavel, R

2012-12-01

Picolinium maleate (PM), an organic material has been synthesised and single crystals were grown by slow evaporation technique. The structure of the grown crystal was elucidated by using single crystal X-ray diffraction analysis. PM crystal belongs to the monoclinic crystallographic system with space group P2(1)/c. The crystalline perfection of the grown crystals was analyzed by high-resolution X-ray diffraction rocking curve measurements. The presence of functional groups in PM was identified by FTIR and FT-NMR spectral analyses. Thermal behaviour and stability of picolinium maleate were studied by TGA/DTA analyses. UV-Vis spectral studies reveal that PM crystals are transparent in the wavelength region 327-1100 nm. The laser damage threshold value of PM crystal was found to be 4.3 GW/cm(2) using Nd:YAG laser. The Kurtz and Perry powder second harmonic generation technique confirms the nonlinear optical property of the grown crystal. Copyright © 2012 Elsevier B.V. All rights reserved.

Validation of a quality-of-life instrument for patients with nonmelanoma skin cancer.

PubMed

Rhee, John S; Matthews, B Alex; Neuburg, Marcy; Logan, Brent R; Burzynski, Mary; Nattinger, Ann B

2006-01-01

To validate a disease-specific quality-of-life instrument--the Skin Cancer Index--intended to measure quality-of-life issues relevant to patients with nonmelanoma skin cancer. Internal reliability, convergent and divergent validity with existing scales, and factor analyses were performed in a cross-sectional study of 211 patients presenting with cervicofacial nonmelanoma skin cancer to a dermatologic surgery clinic. Factor analyses of the Skin Cancer Index confirmed a multidimensional scale with 3 distinct subscales-emotional, social, and appearance. Excellent internal validity of the 3 subscales was demonstrated. Substantial evidence was observed for convergent validity with the Dermatology Life Quality Index, Rosenberg Self-Esteem Scale, Lerman's Cancer Worry Scale, and Medical Outcomes Survey Short-Form 12 domains for vitality, emotion, social function, and mental health. These findings validate a new disease-specific quality-of-life instrument for patients with cervicofacial nonmelanoma skin cancer. Studies on the responsiveness of the Skin Cancer Index to clinical intervention are currently under way.

Immunogenicity is preferentially induced in sparse dendritic cell cultures

PubMed Central

Nasi, Aikaterini; Bollampalli, Vishnu Priya; Sun, Meng; Chen, Yang; Amu, Sylvie; Nylén, Susanne; Eidsmo, Liv; Rothfuchs, Antonio Gigliotti; Réthi, Bence

2017-01-01

We have previously shown that human monocyte-derived dendritic cells (DCs) acquired different characteristics in dense or sparse cell cultures. Sparsity promoted the development of IL-12 producing migratory DCs, whereas dense cultures increased IL-10 production. Here we analysed whether the density-dependent endogenous breaks could modulate DC-based vaccines. Using murine bone marrow-derived DC models we show that sparse cultures were essential to achieve several key functions required for immunogenic DC vaccines, including mobility to draining lymph nodes, recruitment and massive proliferation of antigen-specific CD4+ T cells, in addition to their TH1 polarization. Transcription analyses confirmed higher commitment in sparse cultures towards T cell activation, whereas DCs obtained from dense cultures up-regulated immunosuppressive pathway components and genes suggesting higher differentiation plasticity towards osteoclasts. Interestingly, we detected a striking up-regulation of fatty acid and cholesterol biosynthesis pathways in sparse cultures, suggesting an important link between DC immunogenicity and lipid homeostasis regulation. PMID:28276533

Nanostructured mesoporous silica: new perspectives for fighting antimicrobial resistance

NASA Astrophysics Data System (ADS)

Voicu, Georgeta; Dogaru, Ionuţ; Meliţă, Daniela; Meştercă, Raluca; Spirescu, Vera; Stan, Eliza; Tote, Eliza; Mogoantă, Laurenţiu; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai; Truşcă, Roxana; Vasile, Eugeniu; Iordache, Florin; Chifiriuc, Mariana-Carmen; Holban, Alina Maria

2015-05-01

This paper investigates the antimicrobial potential of nanostructured mesoporous silica (NMS) functionalized with essential oils (EOs) and antibiotics (ATBs). The NMS networks were obtained by the basic procedure from cetyltrimethylammonium bromide and tetraethyl orthosilicate in the form of granules with diameters ranging from 100 to 300 nm with an average pore diameter of 2.2 nm, as confirmed by the BET-TEM analyses. The Salvia officinalis (SO) and Coriandrum sativum (CS) EOs and the streptomycin and neomycin ATBs were loaded in the NMS pores. TG analysis was performed in order to estimate the amount of the entrapped volatile EOs. The results of the biological analyses revealed that NMS/SO and NMS/CS exhibited a very good antimicrobial activity to an extent comparable or even superior to the one triggered by ATB, and a good in vitro and in vivo biocompatibility. Due to their regular pores, high biocompatibility, antimicrobial activity, and capacity to stabilize the volatile EOs, the obtained NMS can be used as an efficient drug delivery system for further biomedical applications.

Dentin and pulp sense cold stimulus.

PubMed

Tokuda, Masayuki; Tatsuyama, Shoko; Fujisawa, Mari; Morimoto-Yamashita, Yoko; Kawakami, Yoshiko; Shibukawa, Yoshiyuki; Torii, Mistuso

2015-05-01

Dentin hypersensitivity is a common symptom, and recent convergent evidences have reported transient receptor potential (TRP) channels in odontoblasts act as mechanical and thermal molecular sensor, which detect stimulation applied on the exposed dentin surface, to drive multiple odontoblastic cellular functions, such as sensory transduction and/or dentin formation. In the present study, we confirmed expression of TRP melastatin subfamily member-8 (TRPM8) channels in primary cultured cells derived from human dental pulp cells (HPCs) and mouse odontoblast-lineage cells (OLCs) as well as in dentin matrix protein-1 (DMP-1) and dentin sialoprotein (DSP) positive acutely isolated rat odontoblasts from dental pulp tissue slice culture by immunohistochemical analyses. In addition, we detected TRPM8 channel expression on HPCs and OLCs by RT-PCR and Western blotting analyses. These results indicated that both odontoblasts and dental pulp cells express TRPM8 channels in rat, mouse and human, and therefore we hypothesize they may contribute as cold sensor in tooth. Copyright © 2015 Elsevier Ltd. All rights reserved.

Detonation Performance Analyses for Recent Energetic Molecules

NASA Astrophysics Data System (ADS)

Stiel, Leonard; Samuels, Philip; Spangler, Kimberly; Iwaniuk, Daniel; Cornell, Rodger; Baker, Ernest

2017-06-01

Detonation performance analyses were conducted for a number of evolving and potential high explosive materials. The calculations were completed for theoretical maximum densities of the explosives using the Jaguar thermo-chemical equation of state computer programs for performance evaluations and JWL/JWLB equations of state parameterizations. A number of recently synthesized materials were investigated for performance characterizations and comparisons to existing explosives, including TNT, RDX, HMX, and Cl-20. The analytic cylinder model was utilized to establish cylinder and Gurney velocities as functions of the radial expansions of the cylinder for each explosive. The densities and heats of formulation utilized in the calculations are primarily experimental values from Picatinny Arsenal and other sources. Several of the new materials considered were predicted to have enhanced detonation characteristics compared to conventional explosives. In order to confirm the accuracy of the Jaguar and analytic cylinder model results, available experimental detonation and Gurney velocities for representative energetic molecules and their formulations were compared with the corresponding calculated values. Close agreement was obtained with most of the data. Presently at NATO.

Progression in structural, magnetic and electrical properties of La-doped group IV elements

NASA Astrophysics Data System (ADS)

Deepapriya, S.; Annie Vinosha, P.; Rodney, John D.; Jerome Das, S.

2018-04-01

Progression of group IV elements such as zinc ferrite (ZnFe2O4), cobalt ferrite (CoFe2O4) was synthesized by doping lanthanum (La), via adopting a facile co-precipitation method. Doping hefty rare earth ion in spinel structure can amend to the physical properties of the lattice, which can be used in the enhancement of magnetic and electrical properties of the as-synthesized nanomaterial, it is vital to metamorphose and optimize its micro structural and magnetic features. The structural properties of the samples was analysed by powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), Transmission electron microscopy (TEM) and UV-visible spectral analysis (UV-vis) reveals the optical property and optical band gap. The magnetic properties were evaluated using a vibrating sample magnetometer (VSM), the presence of functional group was confirmed by FTIR. XRD analyses elucidates that the synthesized samples zinc and cobalt had a spinel structure. From TEM analyses the morphology and diameter of the particle was observed. The substituted rare earth ions in Zinc ferrite inhibit the grain growth of the materials in an efficient manner compared with that of the Cobalt ferrite.

Structural basis for amino acid export by DMT superfamily transporter YddG.

PubMed

Tsuchiya, Hirotoshi; Doki, Shintaro; Takemoto, Mizuki; Ikuta, Tatsuya; Higuchi, Takashi; Fukui, Keita; Usuda, Yoshihiro; Tabuchi, Eri; Nagatoishi, Satoru; Tsumoto, Kouhei; Nishizawa, Tomohiro; Ito, Koichi; Dohmae, Naoshi; Ishitani, Ryuichiro; Nureki, Osamu

2016-06-16

The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 Å resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.

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

Evolution of Homospermidine Synthase in the Convolvulaceae: A Story of Gene Duplication, Gene Loss, and Periods of Various Selection Pressures[C][W][OA

PubMed Central

Kaltenegger, Elisabeth; Eich, Eckart; Ober, Dietrich

2013-01-01

Homospermidine synthase (HSS), the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, is known to have its origin in the duplication of a gene encoding deoxyhypusine synthase. To study the processes that followed this gene duplication event and gave rise to HSS, we identified sequences encoding HSS and deoxyhypusine synthase from various species of the Convolvulaceae. We show that HSS evolved only once in this lineage. This duplication event was followed by several losses of a functional gene copy attributable to gene loss or pseudogenization. Statistical analyses of sequence data suggest that, in those lineages in which the gene copy was successfully recruited as HSS, the gene duplication event was followed by phases of various selection pressures, including purifying selection, relaxed functional constraints, and possibly positive Darwinian selection. Site-specific mutagenesis experiments have confirmed that the substitution of sites predicted to be under positive Darwinian selection is sufficient to convert a deoxyhypusine synthase into a HSS. In addition, analyses of transcript levels have shown that HSS and deoxyhypusine synthase have also diverged with respect to their regulation. The impact of protein–protein interaction on the evolution of HSS is discussed with respect to current models of enzyme evolution. PMID:23572540

Molecular characterization of a microbial consortium involved in methane oxidation coupled to denitrification under micro-aerobic conditions.

PubMed

Liu, Jingjing; Sun, Faqian; Wang, Liang; Ju, Xi; Wu, Weixiang; Chen, Yingxu

2014-01-01

Methane can be used as an alternative carbon source in biological denitrification because it is nontoxic, widely available and relatively inexpensive. A microbial consortium involved in methane oxidation coupled to denitrification (MOD) was enriched with nitrite and nitrate as electron acceptors under micro-aerobic conditions. The 16S rRNA gene combined with pmoA phylogeny of methanotrophs and nirK phylogeny of denitrifiers were analysed to reveal the dominant microbial populations and functional microorganisms. Real-time quantitative polymerase chain reaction results showed high numbers of methanotrophs and denitrifiers in the enriched consortium. The 16S rRNA gene clone library revealed that Methylococcaceae and Methylophilaceae were the dominant populations in the MOD ecosystem. Phylogenetic analyses of pmoA gene clone libraries indicated that all methanotrophs belonged to Methylococcaceae, a type I methanotroph employing the ribulose monophosphate pathway for methane oxidation. Methylotrophic denitrifiers of the Methylophilaceae that can utilize organic intermediates (i.e. formaldehyde, citrate and acetate) released from the methanotrophs played a vital role in aerobic denitrification. This study is the first report to confirm micro-aerobic denitrification and to make phylogenetic and functional assignments for some members of the microbial assemblages involved in MOD. © 2013 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Identification of novel interactors and potential phosphorylation substrates of GsSnRK1 from wild soybean (Glycine soja).

PubMed

Song, Yu; Zhang, Hang; You, Hongguang; Liu, Yuanming; Chen, Chao; Feng, Xu; Yu, Xingyu; Wu, Shengyang; Wang, Libo; Zhong, Shihua; Li, Qiang; Zhu, Yanming; Ding, Xiaodong

2018-04-17

The plant sucrose nonfermenting kinase 1 (SnRK1) kinases play the central roles in the processes of energy balance, hormone perception, stress resistance, metabolism, growth, and development. However, the functions of these kinases are still elusive. In this study, we used GsSnRK1 of wild soybean as bait to perform library-scale screens by the means of yeast two-hybrid to identify its interacting proteins. The putative interactions were verified by yeast retransformation and β-galactosidase assays, and the selected interactions were further confirmed in planta by bimolecular fluorescence complementation and biochemical Co-IP assays. Protein phosphorylation analyses were carried out by phos-tag assay and anti-phospho-(Ser/Thr) substrate antibodies. Finally, we obtained 24 GsSnRK1 interactors and several putative substrates that can be categorized into SnRK1 regulatory β subunit, protein modification, biotic and abiotic stress-related, hormone perception and signalling, gene expression regulation, water and nitrogen transport, metabolism, and unknown proteins. Intriguingly, we first discovered that GsSnRK1 interacted with and phosphorylated the components of soybean nodulation and symbiotic nitrogen fixation. The interactions and potential functions of GsSnRK1 and its associated proteins were extensively discussed and analysed. This work provides plausible clues to elucidate the novel functions of SnRK1 in response to variable environmental, metabolic, and physiological requirements. © 2018 John Wiley & Sons Ltd.

Genomic context drives transcription of insertion sequences in the bacterial endosymbiont Wolbachia wVulC.

PubMed

Cerveau, Nicolas; Gilbert, Clément; Liu, Chao; Garrett, Roger A; Grève, Pierre; Bouchon, Didier; Cordaux, Richard

2015-06-10

Transposable elements (TEs) are DNA pieces that are present in almost all the living world at variable genomic density. Due to their mobility and density, TEs are involved in a large array of genomic modifications. In eukaryotes, TE expression has been studied in detail in several species. In prokaryotes, studies of IS expression are generally linked to particular copies that induce a modification of neighboring gene expression. Here we investigated global patterns of IS transcription in the Alphaproteobacterial endosymbiont Wolbachia wVulC, using both RT-PCR and bioinformatic analyses. We detected several transcriptional promoters in all IS groups. Nevertheless, only one of the potentially functional IS groups possesses a promoter located upstream of the transposase gene, that could lead up to the production of a functional protein. We found that the majority of IS groups are expressed whatever their functional status. RT-PCR analyses indicate that the transcription of two IS groups lacking internal promoters upstream of the transposase start codon may be driven by the genomic environment. We confirmed this observation with the transcription analysis of individual copies of one IS group. These results suggest that the genomic environment is important for IS expression and it could explain, at least partly, copy number variability of the various IS groups present in the wVulC genome and, more generally, in bacterial genomes. Copyright © 2015 Elsevier B.V. All rights reserved.

Cross-cultural adaptation of a pre-school screening instrument: comparison of Korean and US populations.

PubMed

Heo, K H; Squires, J; Yovanoff, P

2008-03-01

Accurate and efficient developmental screening measures are critical for early identification of developmental problems; however, few reliable and valid tests are available in Korea as well as other countries outside the USA. The Ages and Stages Questionnaires (ASQ) was chosen for study with young children in Korea. The ASQ was translated into Korean and necessary cross-cultural adaptations were made. The translated version was then distributed and completed by 3220 parents of young children between the ages of 4 months and 5 years. Reliability was studied including domain correlations, internal consistency, and performance of identification cut-off scores for the Korean population. Rasch analyses including tests of Differential Item Functioning, contrasting Korean and US samples were also performed. In general, internal consistency of the Korean ASQ was high, with overall correlations 0.75 for communication, 0.85 for gross motor, 0.74 for fine motor, 0.72 for problem solving, and 0.65 for personal-social. Validity, including concurrent validity, also had strong evidence. Mean scores of children on the Korean translation of the ASQ and the US normative sample were generally similar. Rasch analyses indicated the majority of items functioned similarly across the Korean sample. In general, the ASQ was translated with cultural appropriateness in mind and functioned as a valid and reliable parent-completed screening test to assist in early identification of young children with developmental delays. Further research is needed to confirm these results with a larger and more diverse Korean sample.

Does physical exposure throughout working life influence chair-rise performance in midlife? A retrospective cohort study of associations between work and physical function in Denmark

PubMed Central

Møller, Anne; Reventlow, Susanne; Hansen, Åse Marie; Andersen, Lars L; Siersma, Volkert; Lund, Rikke; Avlund, Kirsten; Andersen, Johan Hviid; Mortensen, Ole Steen

2015-01-01

Objectives Our aim was to study associations between physical exposures throughout working life and physical function measured as chair-rise performance in midlife. Methods The Copenhagen Aging and Midlife Biobank (CAMB) provided data about employment and measures of physical function. Individual job histories were assigned exposures from a job exposure matrix. Exposures were standardised to ton-years (lifting 1000 kg each day in 1 year), stand-years (standing/walking for 6 h each day in 1 year) and kneel-years (kneeling for 1 h each day in 1 year). The associations between exposure-years and chair-rise performance (number of chair-rises in 30 s) were analysed in multivariate linear and non-linear regression models adjusted for covariates. Results Mean age among the 5095 participants was 59 years in both genders, and, on average, men achieved 21.58 (SD=5.60) and women 20.38 (SD=5.33) chair-rises in 30 s. Physical exposures were associated with poorer chair-rise performance in both men and women, however, only associations between lifting and standing/walking and chair-rise remained statistically significant among men in the final model. Spline regression analyses showed non-linear associations and confirmed the findings. Conclusions Higher physical exposure throughout working life is associated with slightly poorer chair-rise performance. The associations between exposure and outcome were non-linear. PMID:26537502

Identification of new intrinsic proteins in Arabidopsis plasma membrane proteome.

PubMed

Marmagne, Anne; Rouet, Marie-Aude; Ferro, Myriam; Rolland, Norbert; Alcon, Carine; Joyard, Jacques; Garin, Jérome; Barbier-Brygoo, Hélène; Ephritikhine, Geneviève

2004-07-01

Identification and characterization of anion channel genes in plants represent a goal for a better understanding of their central role in cell signaling, osmoregulation, nutrition, and metabolism. Though channel activities have been well characterized in plasma membrane by electrophysiology, the corresponding molecular entities are little documented. Indeed, the hydrophobic protein equipment of plant plasma membrane still remains largely unknown, though several proteomic approaches have been reported. To identify new putative transport systems, we developed a new proteomic strategy based on mass spectrometry analyses of a plasma membrane fraction enriched in hydrophobic proteins. We produced from Arabidopsis cell suspensions a highly purified plasma membrane fraction and characterized it in detail by immunological and enzymatic tests. Using complementary methods for the extraction of hydrophobic proteins and mass spectrometry analyses on mono-dimensional gels, about 100 proteins have been identified, 95% of which had never been found in previous proteomic studies. The inventory of the plasma membrane proteome generated by this approach contains numerous plasma membrane integral proteins, one-third displaying at least four transmembrane segments. The plasma membrane localization was confirmed for several proteins, therefore validating such proteomic strategy. An in silico analysis shows a correlation between the putative functions of the identified proteins and the expected roles for plasma membrane in transport, signaling, cellular traffic, and metabolism. This analysis also reveals 10 proteins that display structural properties compatible with transport functions and will constitute interesting targets for further functional studies.

Sex differences in cerebral palsy incidence and functional ability: a total population study.

PubMed

Chounti, A; Hägglund, G; Wagner, P; Westbom, L

2013-07-01

To describe gender difference in a total population of children with cerebral palsy (CP), related to subtype, gross and fine motor function, and to compare CP incidence trends in girls and boys. All 590 children with CP born in southern Sweden 1990-2005 were included. CP subtype was classified according to the Surveillance of Cerebral Palsy in Europe, gross motor function according to Gross Motor Function Classification System (GMFCS) and manual ability according to Manual Ability Classification System (MACS). Trends in CP incidence by birth year were analysed using Poisson regression modelling. There was a male predominance in all levels of GMFCS except level II, in all levels of MACS and in all CP subtypes except ataxic CP. There was no statistically significant difference between males and females regarding gross motor function or manual ability. The CP incidence trends in boys compared with girls did not change during the period 1990-2005. No equalization was detected in the incidence of CP between girls and boys during recent years in this total population. We could not confirm any consistent sex difference in motor function levels. Male sex is a risk factor for CP. ©2013 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Plant functional trait diversity regulates the nonlinear response of productivity to regional climate change in Tibetan alpine grasslands.

PubMed

Wu, Jianshuang; Wurst, Susanne; Zhang, Xianzhou

2016-10-19

The biodiversity-productivity relationship is still under debate for alpine grasslands on the Tibetan Plateau. We know little about direct and indirect effects of biotic and abiotic drivers on this relationship, especially in regard to plant functional trait diversity. Here, we examine how aboveground net primary productivity (ANPP) and precipitation use efficiency (PUE) respond to climate, soil and community structure across alpine grasslands on the Northern Tibetan Plateau. We found that both ANPP and PUE showed nonlinear patterns along water availability and site altitude variation, which together accounted for 80.3% and 68.8% of variation in ANPP and PUE, respectively, by optimal generalized additive models. Functional trait divergence (FTD) and community weighted mean (CWM) of plant functional traits were as important as plant species diversity (PSD) for explaining the nonlinear productivity-climate relationship. These findings were confirmed by results from principal component analyses and structural equation models. We also found that FTD was negatively correlated with PSD across different alpine grasslands. Our results implicate: first, the combinatorial influences of temperature and precipitation gradients are important for predicting alpine grassland dynamics; second, the convergence and divergence of plant functional traits may have the potential to elucidate the effect of plant diversity on ecosystem functionality.

Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

PubMed

Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

2015-01-01

Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

Plant functional trait diversity regulates the nonlinear response of productivity to regional climate change in Tibetan alpine grasslands

PubMed Central

Wu, Jianshuang; Wurst, Susanne; Zhang, Xianzhou

2016-01-01

The biodiversity-productivity relationship is still under debate for alpine grasslands on the Tibetan Plateau. We know little about direct and indirect effects of biotic and abiotic drivers on this relationship, especially in regard to plant functional trait diversity. Here, we examine how aboveground net primary productivity (ANPP) and precipitation use efficiency (PUE) respond to climate, soil and community structure across alpine grasslands on the Northern Tibetan Plateau. We found that both ANPP and PUE showed nonlinear patterns along water availability and site altitude variation, which together accounted for 80.3% and 68.8% of variation in ANPP and PUE, respectively, by optimal generalized additive models. Functional trait divergence (FTD) and community weighted mean (CWM) of plant functional traits were as important as plant species diversity (PSD) for explaining the nonlinear productivity-climate relationship. These findings were confirmed by results from principal component analyses and structural equation models. We also found that FTD was negatively correlated with PSD across different alpine grasslands. Our results implicate: first, the combinatorial influences of temperature and precipitation gradients are important for predicting alpine grassland dynamics; second, the convergence and divergence of plant functional traits may have the potential to elucidate the effect of plant diversity on ecosystem functionality. PMID:27759112

Functional characterization of rare FOXP2 variants in neurodevelopmental disorder.

PubMed

Estruch, Sara B; Graham, Sarah A; Chinnappa, Swathi M; Deriziotis, Pelagia; Fisher, Simon E

2016-01-01

Heterozygous disruption of FOXP2 causes a rare form of speech and language impairment. Screens of the FOXP2 sequence in individuals with speech/language-related disorders have identified several rare protein-altering variants, but their phenotypic relevance is often unclear. FOXP2 encodes a transcription factor with a forkhead box DNA-binding domain, but little is known about the functions of protein regions outside this domain. We performed detailed functional analyses of seven rare FOXP2 variants found in affected cases, including three which have not been previously characterized, testing intracellular localization, transcriptional regulation, dimerization, and interaction with other proteins. To shed further light on molecular functions of FOXP2, we characterized the interaction between this transcription factor and co-repressor proteins of the C-terminal binding protein (CTBP) family. Finally, we analysed the functional significance of the polyglutamine tracts in FOXP2, since tract length variations have been reported in cases of neurodevelopmental disorder. We confirmed etiological roles of multiple FOXP2 variants. Of three variants that have been suggested to cause speech/language disorder, but never before been characterized, only one showed functional effects. For the other two, we found no effects on protein function in any assays, suggesting that they are incidental to the phenotype. We identified a CTBP-binding region within the N-terminal portion of FOXP2. This region includes two amino acid substitutions that occurred on the human lineage following the split from chimpanzees. However, we did not observe any effects of these amino acid changes on CTBP binding or other core aspects of FOXP2 function. Finally, we found that FOXP2 variants with reduced polyglutamine tracts did not exhibit altered behaviour in cellular assays, indicating that such tracts are non-essential for core aspects of FOXP2 function, and that tract variation is unlikely to be a highly penetrant cause of speech/language disorder. Our findings highlight the importance of functional characterization of novel rare variants in FOXP2 in assessing the contribution of such variants to speech/language disorder and provide further insights into the molecular function of the FOXP2 protein.

Episodic memory impairment in Addison's disease: results from a telephonic cognitive assessment.

PubMed

Henry, Michelle; Thomas, Kevin G F; Ross, Ian L

2014-06-01

Patients with Addison's disease frequently self-report memory and attention difficulties, even when on standard replacement therapy. However, few published studies examine, using objective measures and assessing across multiple domains, the cognitive functioning of Addison's disease patients relative to healthy controls. The primary aim of this study was to investigate whether the previously reported subjective cognitive deficits in Addison's disease are confirmed by objective measures. Conducting comprehensive neuropsychological assessments of patients with relatively rare clinical disorders, such as Addison's disease, is challenging because access to those patients is often limited, and because their medical condition might prevent extended testing sessions. Brief telephonic cognitive assessments are a useful tool in such circumstances. Hence, we administered the Brief Test of Adult Cognition by Telephone to 27 Addison's disease patients and 27 matched healthy controls. The instrument provides objective assessment of episodic memory, working memory, executive functioning, reasoning, and speed of processing. Statistical analyses confirmed that, as expected, patients performed significantly more poorly than controls on the episodic memory subtest. There were, however, no significant between-group differences on the attention, executive functioning, reasoning, and speed of processing subtests. Furthermore, patients with a longer duration of illness performed more poorly across all domains of cognition. We conclude that, for Addison's disease patients, previously reported subjective cognitive deficits are matched by objective impairment, but only in the domain of episodic memory. Future research might investigate (a) whether these memory deficits are material-specific (i.e., whether non-verbal memory is also affected), and (b) the neurobiological mechanisms underlying these deficits.

Multiomics reveal non-alcoholic fatty liver disease in rats following chronic exposure to an ultra-low dose of Roundup herbicide

PubMed Central

Mesnage, Robin; Renney, George; Séralini, Gilles-Eric; Ward, Malcolm; Antoniou, Michael N.

2017-01-01

The impairment of liver function by low environmentally relevant doses of glyphosate-based herbicides (GBH) is still a debatable and unresolved matter. Previously we have shown that rats administered for 2 years with 0.1 ppb (50 ng/L glyphosate equivalent dilution; 4 ng/kg body weight/day daily intake) of a Roundup GBH formulation showed signs of enhanced liver injury as indicated by anatomorphological, blood/urine biochemical changes and transcriptome profiling. Here we present a multiomic study combining metabolome and proteome liver analyses to obtain further insight into the Roundup-induced pathology. Proteins significantly disturbed (214 out of 1906 detected, q < 0.05) were involved in organonitrogen metabolism and fatty acid β-oxidation. Proteome disturbances reflected peroxisomal proliferation, steatosis and necrosis. The metabolome analysis (55 metabolites altered out of 673 detected, p < 0.05) confirmed lipotoxic conditions and oxidative stress by showing an activation of glutathione and ascorbate free radical scavenger systems. Additionally, we found metabolite alterations associated with hallmarks of hepatotoxicity such as γ-glutamyl dipeptides, acylcarnitines, and proline derivatives. Overall, metabolome and proteome disturbances showed a substantial overlap with biomarkers of non-alcoholic fatty liver disease and its progression to steatohepatosis and thus confirm liver functional dysfunction resulting from chronic ultra-low dose GBH exposure. PMID:28067231

Metagenomic and metabolic profiling of nonlithifying and lithifying stromatolitic mats of Highborne Cay, The Bahamas.

PubMed

Khodadad, Christina L M; Foster, Jamie S

2012-01-01

Stromatolites are laminated carbonate build-ups formed by the metabolic activity of microbial mats and represent one of the oldest known ecosystems on Earth. In this study, we examined a living stromatolite located within the Exuma Sound, The Bahamas and profiled the metagenome and metabolic potential underlying these complex microbial communities. The metagenomes of the two dominant stromatolitic mat types, a nonlithifying (Type 1) and lithifying (Type 3) microbial mat, were partially sequenced and compared. This deep-sequencing approach was complemented by profiling the substrate utilization patterns of the mats using metabolic microarrays. Taxonomic assessment of the protein-encoding genes confirmed previous SSU rRNA analyses that bacteria dominate the metagenome of both mat types. Eukaryotes comprised less than 13% of the metagenomes and were rich in sequences associated with nematodes and heterotrophic protists. Comparative genomic analyses of the functional genes revealed extensive similarities in most of the subsystems between the nonlithifying and lithifying mat types. The one exception was an increase in the relative abundance of certain genes associated with carbohydrate metabolism in the lithifying Type 3 mats. Specifically, genes associated with the degradation of carbohydrates commonly found in exopolymeric substances, such as hexoses, deoxy- and acidic sugars were found. The genetic differences in carbohydrate metabolisms between the two mat types were confirmed using metabolic microarrays. Lithifying mats had a significant increase in diversity and utilization of carbon, nitrogen, phosphorus and sulfur substrates. The two stromatolitic mat types retained similar microbial communities, functional diversity and many genetic components within their metagenomes. However, there were major differences detected in the activity and genetic pathways of organic carbon utilization. These differences provide a strong link between the metagenome and the physiology of the mats, as well as new insights into the biological processes associated with carbonate precipitation in modern marine stromatolites.

The Proteome of Native Adult Müller Glial Cells From Murine Retina*

PubMed Central

Hauser, Alexandra; Lepper, Marlen Franziska; Mayo, Rebecca

2016-01-01

To date, the proteomic profiling of Müller cells, the dominant macroglia of the retina, has been hampered because of the absence of suitable enrichment methods. We established a novel protocol to isolate native, intact Müller cells from adult murine retinae at excellent purity which retain in situ morphology and are well suited for proteomic analyses. Two different strategies of sample preparation - an in StageTips (iST) and a subcellular fractionation approach including cell surface protein profiling were used for quantitative liquid chromatography-mass spectrometry (LC-MSMS) comparing Müller cell-enriched to depleted neuronal fractions. Pathway enrichment analyses on both data sets enabled us to identify Müller cell-specific functions which included focal adhesion kinase signaling, signal transduction mediated by calcium as second messenger, transmembrane neurotransmitter transport and antioxidant activity. Pathways associated with RNA processing, cellular respiration and phototransduction were enriched in the neuronal subpopulation. Proteomic results were validated for selected Müller cell genes by quantitative real time PCR, confirming the high expression levels of numerous members of the angiogenic and anti-inflammatory annexins and antioxidant enzymes (e.g. paraoxonase 2, peroxiredoxin 1, 4 and 6). Finally, the significant enrichment of antioxidant proteins in Müller cells was confirmed by measurements on vital retinal cells using the oxidative stress indicator CM-H2DCFDA. In contrast to photoreceptors or bipolar cells, Müller cells were most efficiently protected against H2O2-induced reactive oxygen species formation, which is in line with the protein repertoire identified in the proteomic profiling. Our novel approach to isolate intact glial cells from adult retina in combination with proteomic profiling enabled the identification of novel Müller glia specific proteins, which were validated as markers and for their functional impact in glial physiology. This provides the basis to allow the discovery of novel glial specializations and will enable us to elucidate the role of Müller cells in retinal pathologies — a topic still controversially discussed. PMID:26324419

Synthesis, structural and spectral characterization of a novel NLO crystal N,N‧-diphenylguanidinium picrate: diacetone solvate

NASA Astrophysics Data System (ADS)

Shanmugavadivu, T.; Dhandapani, M.; Naveen, S.; Lokanath, N. K.

2017-09-01

An organic NLO active material N,N‧-diphenylguanidinium picrate: diacetone solvate (C13H14N3+. C6H2N3O7-. 2C3H6O) (DPGPD) was synthesized and single crystals were grown by slow evaporation-solution growth technique at room temperature. DPGPD crystallizes in monoclinic crystal system with noncentrosymmetric space group, Cc confirmed by single crystal X-ray diffraction analysis. The presence of various functional groups was identified from FT-IR spectral analysis and the proton transfer during the formation of compound was confirmed by NMR spectroscopic techniques. The thermal stability was investigated by TG/DTA analyses. Optical transmittance was measured by UV-Vis-NIR spectroscopy and band gap energy was calculated. Photoluminescence spectrum was used to explore its applicability towards laser diodes. Dielectric property of the material was ascertained at different temperatures and it is found that the grown crystal has higher dielectric constant in low frequencies. Photoconductivity study revealed that DPGPD exhibits positive photoconductivity. SHG property was found to be 0.6 times higher than that of KDP.

Investigations on synthesis, growth and physicochemical properties of semi-organic NLO crystal bis(thiourea) ammonium nitrate for nonlinear frequency conversion

NASA Astrophysics Data System (ADS)

Anbarasi, A.; Ravi Kumar, S. M.; Sundar, G. J. Shanmuga; Mosses, M. Allen; Raj, M. Packiya; Prabhakaran, M.; Ravisankar, R.; Gunaseelan, R.

2017-10-01

Bis(thiourea) ammonium nitrate (BTAN), a new nonlinear optical crystal was grown successfully by slow evaporation technique using water as solvent at room temperature. The grown crystals were optically good quality with dimensions upto 10 × 6 × 3 mm3. Single crystal X-Ray diffraction analysis reveals that the crystal lattice is orthorhombic. From Powder X-ray diffraction analysis the diffraction planes have been indexed. The presence of the various functional groups of BTAN was identified through FTIR spectroscopic analysis. UV cut-off wavelength was observed from optical absorbance spectrum and it was found to be 240 nm. Second harmonic efficiency was determined using Kurtz powder method in comparison with KDP to confirm the nonlinearity of the material. Thermal analysis confirmed that grown crystal is thermally stable upto 184 °C. Microhardness studies show that hardness number (Hv) increases with load. Conductivity measurements such as dielectric, ac and photoconductivity were studied. Growth mechanism and surface features of the as grown single crystal was analysed by chemical etching analysis.

An integrative neural model of social perception, action observation, and theory of mind.

PubMed

Yang, Daniel Y-J; Rosenblau, Gabriela; Keifer, Cara; Pelphrey, Kevin A

2015-04-01

In the field of social neuroscience, major branches of research have been instrumental in describing independent components of typical and aberrant social information processing, but the field as a whole lacks a comprehensive model that integrates different branches. We review existing research related to the neural basis of three key neural systems underlying social information processing: social perception, action observation, and theory of mind. We propose an integrative model that unites these three processes and highlights the posterior superior temporal sulcus (pSTS), which plays a central role in all three systems. Furthermore, we integrate these neural systems with the dual system account of implicit and explicit social information processing. Large-scale meta-analyses based on Neurosynth confirmed that the pSTS is at the intersection of the three neural systems. Resting-state functional connectivity analysis with 1000 subjects confirmed that the pSTS is connected to all other regions in these systems. The findings presented in this review are specifically relevant for psychiatric research especially disorders characterized by social deficits such as autism spectrum disorder. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comprehensive phylogeny of auxin homeostasis genes involved in adventitious root formation in carnation stem cuttings.

PubMed

Sánchez-García, Ana Belén; Ibáñez, Sergio; Cano, Antonio; Acosta, Manuel; Pérez-Pérez, José Manuel

2018-01-01

Understanding the functional basis of auxin homeostasis requires knowledge about auxin biosynthesis, auxin transport and auxin catabolism genes, which is not always directly available despite the recent whole-genome sequencing of many plant species. Through sequence homology searches and phylogenetic analyses on a selection of 11 plant species with high-quality genome annotation, we identified the putative gene homologs involved in auxin biosynthesis, auxin catabolism and auxin transport pathways in carnation (Dianthus caryophyllus L.). To deepen our knowledge of the regulatory events underlying auxin-mediated adventitious root formation in carnation stem cuttings, we used RNA-sequencing data to confirm the expression profiles of some auxin homeostasis genes during the rooting of two carnation cultivars with different rooting behaviors. We also confirmed the presence of several auxin-related metabolites in the stem cutting tissues. Our findings offer a comprehensive overview of auxin homeostasis genes in carnation and provide a solid foundation for further experiments investigating the role of auxin homeostasis in the regulation of adventitious root formation in carnation.

A comprehensive phylogeny of auxin homeostasis genes involved in adventitious root formation in carnation stem cuttings

PubMed Central

Cano, Antonio; Acosta, Manuel

2018-01-01

Understanding the functional basis of auxin homeostasis requires knowledge about auxin biosynthesis, auxin transport and auxin catabolism genes, which is not always directly available despite the recent whole-genome sequencing of many plant species. Through sequence homology searches and phylogenetic analyses on a selection of 11 plant species with high-quality genome annotation, we identified the putative gene homologs involved in auxin biosynthesis, auxin catabolism and auxin transport pathways in carnation (Dianthus caryophyllus L.). To deepen our knowledge of the regulatory events underlying auxin-mediated adventitious root formation in carnation stem cuttings, we used RNA-sequencing data to confirm the expression profiles of some auxin homeostasis genes during the rooting of two carnation cultivars with different rooting behaviors. We also confirmed the presence of several auxin-related metabolites in the stem cutting tissues. Our findings offer a comprehensive overview of auxin homeostasis genes in carnation and provide a solid foundation for further experiments investigating the role of auxin homeostasis in the regulation of adventitious root formation in carnation. PMID:29709027

An integrative neural model of social perception, action observation, and theory of mind

PubMed Central

Yang, Daniel Y.-J.; Rosenblau, Gabriela; Keifer, Cara; Pelphrey, Kevin A.

2016-01-01

In the field of social neuroscience, major branches of research have been instrumental in describing independent components of typical and aberrant social information processing, but the field as a whole lacks a comprehensive model that integrates different branches. We review existing research related to the neural basis of three key neural systems underlying social information processing: social perception, action observation, and theory of mind. We propose an integrative model that unites these three processes and highlights the posterior superior temporal sulcus (pSTS), which plays a central role in all three systems. Furthermore, we integrate these neural systems with the dual system account of implicit and explicit social information processing. Large-scale meta-analyses based on Neurosynth confirmed that the pSTS is at the intersection of the three neural systems. Resting-state functional connectivity analysis with 1000 subjects confirmed that the pSTS is connected to all other regions in these systems. The findings presented in this review are specifically relevant for psychiatric research especially disorders characterized by social deficits such as autism spectrum disorder. PMID:25660957

When Significant Others Suffer: German Validation of the Burden Assessment Scale (BAS)

PubMed Central

Hunger, Christina; Krause, Lena; Hilzinger, Rebecca; Ditzen, Beate; Schweitzer, Jochen

2016-01-01

There is a need of an economical, reliable, and valid instrument in the German-speaking countries to measure the burden of relatives who care for mentally ill persons. We translated the Burden Assessment Scale (BAS) and conducted a study investigating factor structure, psychometric quality and predictive validity. We used confirmative factor analyses (CFA, maximum-likelihood method) to examine the dimensionality of the German BAS in a sample of 215 relatives (72% women; M = 32 years, SD = 14, range: 18 to 77; 39% employed) of mentally ill persons (50% (ex-)partner or (best) friend; M = 32 years, SD = 13, range 8 to 64; main complaints were depression and/or anxiety). Cronbach’s α determined the internal consistency. We examined predictive validity using regression analyses including the BAS and validated scales of social systems functioning (Experience In Social Systems Questionnaire, EXIS.pers, EXIS.org) and psychopathology (Brief Symptom Inventory, BSI). Variables that might have influenced the dependent variables (e.g. age, gender, education, employment and civil status) were controlled by their introduction in the first step, and the BAS in the second step of the regression analyses. A model with four correlated factors (Disrupted Activities, Personal Distress, Time Perspective, Guilt) showed the best fit. With respect to the number of items included, the internal consistency was very good. The modified German BAS predicted relatives’ social systems functioning and psychopathology. The economical design makes the 19-item BAS promising for practice-oriented research, and for studies under time constraints. Strength, limitations and future directions are discussed. PMID:27764109

The alpha subunit of Go interacts with promyelocytic leukemia zinc finger protein and modulates its functions.

PubMed

Won, Jung Hee; Park, Jung Sik; Ju, Hyun Hee; Kim, Soyeon; Suh-Kim, Haeyoung; Ghil, Sung Ho

2008-05-01

Heterotrimeric GTP-binding proteins (G proteins) mediate signal transduction generated by neurotransmitters and hormones. Go, a member of the Go/Gi family, is the most abundant heterotrimeric G protein in the brain. Most mechanistic analyses on Go activation demonstrate that its action is mediated by the Gbetagamma dimer; downstream effectors for its alpha subunit (Goalpha) have not been clearly defined. Here, we employ the yeast two-hybrid system to screen for Goalpha-interacting partners in a cDNA library from human fetal brain. The transcription factor promyelocytic leukemia zinc finger protein (PLZF) specifically bound to Goalpha. Interactions between PLZF and Goalpha were confirmed using in vitro and in vivo affinity binding assays. Activated Goalpha interacted directly with PLZF, and enhanced its function as a transcriptional and cell growth suppressor. Notably, PLZF activity was additionally promoted by the Go/ialpha-coupled cannabinoid receptor (CB) in HL60 cells endogenously expressing CB and PLZF. These results collectively suggest that Goalpha modulates the function of PLZF via direct interactions. Our novel findings provide insights into the diverse cellular roles of Goalpha and its coupled receptor.

Identification and molecular characterisation of a homozygous missense mutation in the ADAMTS10 gene in a patient with Weill-Marchesani syndrome.

PubMed

Steinkellner, Hannes; Etzler, Julia; Gogoll, Laura; Neesen, Jürgen; Stifter, Eva; Brandau, Oliver; Laccone, Franco

2015-09-01

Weill-Marchesani syndrome is a rare disorder of the connective tissue. Functional variants in ADAMTS10 are associated with Weill-Marchesani syndrome-1. We identified a homozygous missense mutation, c.41T>A, of the ADAMTS10 gene in a 19-year-old female with typical symptoms of WMS1: proportionate short stature, brachydactyly, joint stiffness, and microspherophakia. The ADAMTS10 missense mutation was analysed in silico, with conflicting results as to its effects on protein function, but it was predicted to affect the leader sequence. Molecular characterisation in HEK293 Ebna cells revealed an intracellular mis-targeting of the ADAMTS10 protein with a reduced concentration of the polypeptide in the endoplasmic reticulum. A large reduction in glycosylation of the cytoplasmic fraction of the mutant ADAMTS10 protein versus the wild-type protein and a lack of secretion of the mutant protein are also evident in our results.In conclusion, we identified a novel missense mutation of the ADAMTS10 gene and confirmed the functional consequences suggested by the in silico analysis by conducting molecular studies.

Genome-wide identification and expression analysis of the ClTCP transcription factors in Citrullus lanatus.

PubMed

Shi, Pibiao; Guy, Kateta Malangisha; Wu, Weifang; Fang, Bingsheng; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

2016-04-12

The plant-specific TCP transcription factor family, which is involved in the regulation of cell growth and proliferation, performs diverse functions in multiple aspects of plant growth and development. However, no comprehensive analysis of the TCP family in watermelon (Citrullus lanatus) has been undertaken previously. A total of 27 watermelon TCP encoding genes distributed on nine chromosomes were identified. Phylogenetic analysis clustered the genes into 11 distinct subgroups. Furthermore, phylogenetic and structural analyses distinguished two homology classes within the ClTCP family, designated Class I and Class II. The Class II genes were differentiated into two subclasses, the CIN subclass and the CYC/TB1 subclass. The expression patterns of all members were determined by semi-quantitative PCR. The functions of two ClTCP genes, ClTCP14a and ClTCP15, in regulating plant height were confirmed by ectopic expression in Arabidopsis wild-type and ortholog mutants. This study represents the first genome-wide analysis of the watermelon TCP gene family, which provides valuable information for understanding the classification and functions of the TCP genes in watermelon.

Local structure in anisotropic systems determined by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Komolkin, Andrei V.; Maliniak, Arnold

In the present communication we describe the investigation of local structure using a new visualization technique. The approach is based on two-dimensional pair correlation functions derived from a molecular dynamics computer simulation. We have used this method to analyse a trajectory produced in a simulation of a nematic liquid crystal of 4-n-pentyl-4'-cyanobiphenyl (5CB) (Komolkin et al., 1994, J. chem. Phys., 101, 4103). The molecule is assumed to have cylindrical symmetry, and the liquid crystalline phase is treated as uniaxial. The pair correlation functions or cylindrical distribution functions (CDFs) are calculated in the molecular (m) and laboratory (l) frames, gm2(z1 2, d1 2) and g12(Z1 2, D1 2). Anisotropic molecular organization in the liquid crystal is reflected in laboratory frame CDFs. The molecular excluded volume is determined and the effect of the fast motion in the alkyl chain is observed. The intramolecular distributions are included in the CDFs and indicate the size of the motional amplitude in the chain. Absence of long range order was confirmed, a feature typical for a nematic liquid crystal.

Productivity and salinity structuring of the microplankton revealed by comparative freshwater metagenomics

PubMed Central

Eiler, Alexander; Zaremba-Niedzwiedzka, Katarzyna; Martínez-García, Manuel; McMahon, Katherine D; Stepanauskas, Ramunas; Andersson, Siv G E; Bertilsson, Stefan

2014-01-01

Little is known about the diversity and structuring of freshwater microbial communities beyond the patterns revealed by tracing their distribution in the landscape with common taxonomic markers such as the ribosomal RNA. To address this gap in knowledge, metagenomes from temperate lakes were compared to selected marine metagenomes. Taxonomic analyses of rRNA genes in these freshwater metagenomes confirm the previously reported dominance of a limited subset of uncultured lineages of freshwater bacteria, whereas Archaea were rare. Diversification into marine and freshwater microbial lineages was also reflected in phylogenies of functional genes, and there were also significant differences in functional beta-diversity. The pathways and functions that accounted for these differences are involved in osmoregulation, active transport, carbohydrate and amino acid metabolism. Moreover, predicted genes orthologous to active transporters and recalcitrant organic matter degradation were more common in microbial genomes from oligotrophic versus eutrophic lakes. This comparative metagenomic analysis allowed us to formulate a general hypothesis that oceanic- compared with freshwater-dwelling microorganisms, invest more in metabolism of amino acids and that strategies of carbohydrate metabolism differ significantly between marine and freshwater microbial communities. PMID:24118837

Dopamine-Secreting Paraganglioma in the Retroperitoneum.

PubMed

Matsuda, Yusuke; Kimura, Noriko; Yoshimoto, Takanobu; Sekiguchi, Yoshihiro; Tomoishi, Junzo; Kasahara, Ichiro; Hara, Yoshihito; Ogawa, Yoshihiro

2017-03-01

Pheochromocytomas and paragangliomas, which exclusively produce dopamine, are very rare. Herein, we report for the first time a Japanese case of an exclusively dopamine-producing paraganglioma accompanied by detailed immunohistochemical analyses. A 70-year-old Japanese woman was referred to our hospital for functional examination of her left retroperitoneal mass. Her adrenal functions were normal, except for excessive dopamine secretion. After the tumorectomy, her dopamine level normalized. The histopathological diagnosis of the tumor was paraganglioma; this was confirmed by positive immunostaining of chromogranin A (CgA), tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and succinate dehydrogenase gene subunit B (SDHB). However, the immunostaining of CgA in the tumor cells showed peculiar dot-like staining located corresponding to Golgi complex in the perinuclear area, rather than the diffuse cytoplasmic staining usually observed in epinephrine- or norepinephrine-producing functional pheochromocytomas and paragangliomas. The immunohistochemical results suggested that the tumor cells had sparse neuroendocrine granules in the cytoplasm, resulting in inhibition of catecholamine synthesis from dopamine to norepinephrine in neurosecretory granules. This may be the mechanism responsible for exclusive dopamine secretion in the present case.

Crystal Structures of Phd-Doc, HigA, and YeeU Establish Multiple Evolutionary Links between Microbial Growth-Regulating Toxin-Antitoxin Systems

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

Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.

2010-09-27

Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less

Threading the biophysics of mammalian Slo1 channels onto structures of an invertebrate Slo1 channel

PubMed Central

2017-01-01

For those interested in the machinery of ion channel gating, the Ca2+ and voltage-activated BK K+ channel provides a compelling topic for investigation, by virtue of its dual allosteric regulation by both voltage and intracellular Ca2+ and because its large-single channel conductance facilitates detailed kinetic analysis. Over the years, biophysical analyses have illuminated details of the allosteric regulation of BK channels and revealed insights into the mechanism of BK gating, e.g., inner cavity size and accessibility and voltage sensor-pore coupling. Now the publication of two structures of an Aplysia californica BK channel—one liganded and one metal free—promises to reinvigorate functional studies and interpretation of biophysical results. The new structures confirm some of the previous functional inferences but also suggest new perspectives regarding cooperativity between Ca2+-binding sites and the relationship between voltage- and Ca2+-dependent gating. Here we consider the extent to which the two structures explain previous functional data on pore-domain properties, voltage-sensor motions, and divalent cation binding and activation of the channel. PMID:29025867

SiGe derivatization by spontaneous reduction of aryl diazonium salts

NASA Astrophysics Data System (ADS)

Girard, A.; Geneste, F.; Coulon, N.; Cardinaud, C.; Mohammed-Brahim, T.

2013-10-01

Germanium semiconductors have interesting properties for FET-based biosensor applications since they possess high surface roughness allowing the immobilization of a high amount of receptors on a small surface area. Since SiGe combined low cost of Si and intrinsic properties of Ge with high mobility carriers, we focused the study on this particularly interesting material. The comparison of the efficiency of a functionalization process involving the spontaneous reduction of diazonium salts is studied on Si(1 0 0), SiGe and Ge semiconductors. XPS analysis of the functionalized surfaces reveals the presence of a covalent grafted layer on all the substrates that was confirmed by AFM. Interestingly, the modified Ge derivatives have still higher surface roughness after derivatization. To support the estimated thickness by XPS, a step measurement of the organic layers is done by AFM or by profilometer technique after a O2 plasma etching of the functionalized layer. This original method is well-adapted to measure the thickness of thin organic films on rough substrates such as germanium. The analyses show a higher chemical grafting on SiGe substrates compared with Si and Ge semiconductors.

Structure and function of primitive immunoglobulin superfamily neural cell adhesion molecules: a lesson from studies on planarian.

PubMed

Fusaoka, Eri; Inoue, Takeshi; Mineta, Katsuhiko; Agata, Kiyokazu; Takeuchi, Kosei

2006-05-01

Precise wiring and proper remodeling of the neural network are essential for its normal function. The freshwater planarian is an attractive animal in which to study the formation and maintenance of the neural network due to its high regenerative capability and developmental plasticity. Although a recent study revealed that homologs of netrin and its receptors are required for regeneration and maintenance of the planarian central nervous system (CNS), the roles of cell adhesion in the formation and maintenance of the planarian neural network remain poorly understood. In the present study, we found primitive immunoglobulin superfamily cell adhesion molecules (IgCAMs) in a planarian that are homologous to vertebrate neural IgCAMs. We identified planarian orthologs of NCAM, L1CAM, contactin and DSCAM, and designated them DjCAM, DjLCAM, DjCTCAM and DjDSCAM, respectively. We further confirmed that they function as cell adhesion molecules using cell aggregation assays. DjCAM and DjDSCAM were found to be differentially expressed in the CNS. Functional analyses using RNA interference revealed that DjCAM is partly involved in axon formation, and that DjDSCAM plays crucial roles in neuronal cell migration, axon outgrowth, fasciculation and projection.

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

Bipolar patients' quality of life in mixed states: a preliminary qualitative study.

PubMed

Lee Mortensen, Gitte; Vinberg, Maj; Lee Mortensen, Steen; Balslev Jørgensen, Martin; Eberhard, Jonas

2015-01-01

Approximately 20% of patients with bipolar disorder experience mixed states. Mixed states are associated with more comorbidity, poorer treatment response and prognosis, increased relapse rate, and decreased functioning. This study aimed to produce in-depth knowledge about bipolar patients' quality of life (QoL) and functioning related to mixed states. This study used qualitative research methods. A semi-structured interview guide based on a literature study was applied in interviews with 6 remitted bipolar I patients having experienced mixed states. A medical anthropological approach was applied to analyse the data. Participants described mixed states as worse than other bipolar disorder states and their residual symptoms were prolonged. Mixed states affected the functioning of patients in key life domains such as self-esteem, family, love and social life, physical well-being, and working capability. Mixed states may severely affect the QoL and functioning of bipolar patients. Our results indicate that improving these should be a main goal of patient treatment. With an aim of adequately identifying and treating mixed states, our findings highlight the need for knowledge about this particularly severe expression of bipolar disorder. These results should be confirmed in a larger sample of patients with varying socioeconomic status.

Vitality at work and its associations with lifestyle, self-determination, organizational culture, and with employees' performance and sustainable employability.

PubMed

van Scheppingen, Arjella R; de Vroome, Ernest M M; Ten Have, Kristin C J M; Zwetsloot, Gerard I J M; Wiezer, Noortje; van Mechelen, Willem

2015-01-01

Vitality at work is an important factor for optimal functioning and sustainable employability. To date, knowledge on how to promote vitality at work is fragmented. Contribute to knowledge on how to promote vitality at work. Determinants of vitality at work are identified from three scientific fields, and used in a comprehensive model. Regression analyses on cross-sectional data from a Dutch dairy company (N= 629) are performed to examine the associations between these factors, vitality at work, and employees' perceived effective personal functioning and sustainable employability. Vitality at work is most strongly associated with basic psychological needs of self-determination, but also with healthy lifestyle behavior, having a balanced workstyle, and social capital. Vitality at work is also associated with effective personal functioning and with sustainable employability. The study confirms the multifactorial nature of vitality at work. Since organizational culture may support self-determination, and cultural aspects themselves are positively associated with vitality, organizational culture seems particular important in promoting vitality at work. Additionally, a healthy lifestyle appears important. The associations between vitality at work and effective personal functioning and sustainable employability endorse the combined health-based, business-related and societal importance of vitality at work.

Tomographic local 2D analyses of the WISExSuperCOSMOS all-sky galaxy catalogue

NASA Astrophysics Data System (ADS)

Novaes, C. P.; Bernui, A.; Xavier, H. S.; Marques, G. A.

2018-05-01

The recent progress in obtaining larger and deeper galaxy catalogues is of fundamental importance for cosmological studies, especially to robustly measure the large scale density fluctuations in the Universe. The present work uses the Minkowski Functionals (MF) to probe the galaxy density field from the WISExSuperCOSMOS (WSC) all-sky catalogue by performing tomographic local analyses in five redshift shells (of thickness δz = 0.05) in the total range of 0.10 < z < 0.35. Here, for the first time, the MF are applied to 2D projections of the galaxy number count (GNC) fields with the purpose of looking for regions in the WSC catalogue with unexpected features compared to ΛCDM mock realisations. Our methodology reveals 1 - 3 regions of the GNC maps in each redshift shell with an uncommon behaviour (extreme regions), i.e., p-value < 1.4%. Indeed, the resulting MF curves show signatures that suggest the uncommon behaviour to be associated with the presence of over- or under-densities there, but contamination due to residual foregrounds is not discarded. Additionally, even though our analyses indicate a good agreement among data and simulations, we identify 1 highly extreme region, seemingly associated to a large clustered distribution of galaxies. Our results confirm the usefulness of the MF to analyse GNC maps from photometric galaxy datasets.

Functional networks inference from rule-based machine learning models.

PubMed

Lazzarini, Nicola; Widera, Paweł; Williamson, Stuart; Heer, Rakesh; Krasnogor, Natalio; Bacardit, Jaume

2016-01-01

Functional networks play an important role in the analysis of biological processes and systems. The inference of these networks from high-throughput (-omics) data is an area of intense research. So far, the similarity-based inference paradigm (e.g. gene co-expression) has been the most popular approach. It assumes a functional relationship between genes which are expressed at similar levels across different samples. An alternative to this paradigm is the inference of relationships from the structure of machine learning models. These models are able to capture complex relationships between variables, that often are different/complementary to the similarity-based methods. We propose a protocol to infer functional networks from machine learning models, called FuNeL. It assumes, that genes used together within a rule-based machine learning model to classify the samples, might also be functionally related at a biological level. The protocol is first tested on synthetic datasets and then evaluated on a test suite of 8 real-world datasets related to human cancer. The networks inferred from the real-world data are compared against gene co-expression networks of equal size, generated with 3 different methods. The comparison is performed from two different points of view. We analyse the enriched biological terms in the set of network nodes and the relationships between known disease-associated genes in a context of the network topology. The comparison confirms both the biological relevance and the complementary character of the knowledge captured by the FuNeL networks in relation to similarity-based methods and demonstrates its potential to identify known disease associations as core elements of the network. Finally, using a prostate cancer dataset as a case study, we confirm that the biological knowledge captured by our method is relevant to the disease and consistent with the specialised literature and with an independent dataset not used in the inference process. The implementation of our network inference protocol is available at: http://ico2s.org/software/funel.html.

The Effect of Functional Hearing and Hearing Aid Usage on Verbal Reasoning in a Large Community-Dwelling Population.

PubMed

Keidser, Gitte; Rudner, Mary; Seeto, Mark; Hygge, Staffan; Rönnberg, Jerker

2016-01-01

Verbal reasoning performance is an indicator of the ability to think constructively in everyday life and relies on both crystallized and fluid intelligence. This study aimed to determine the effect of functional hearing on verbal reasoning when controlling for age, gender, and education. In addition, the study investigated whether hearing aid usage mitigated the effect and examined different routes from hearing to verbal reasoning. Cross-sectional data on 40- to 70-year-old community-dwelling participants from the UK Biobank resource were accessed. Data consisted of behavioral and subjective measures of functional hearing, assessments of numerical and linguistic verbal reasoning, measures of executive function, and demographic and lifestyle information. Data on 119,093 participants who had completed hearing and verbal reasoning tests were submitted to multiple regression analyses, and data on 61,688 of these participants, who had completed additional cognitive tests and provided relevant lifestyle information, were submitted to structural equation modeling. Poorer performance on the behavioral measure of functional hearing was significantly associated with poorer verbal reasoning in both the numerical and linguistic domains (p < 0.001). There was no association between the subjective measure of functional hearing and verbal reasoning. Functional hearing significantly interacted with education (p < 0.002), showing a trend for functional hearing to have a greater impact on verbal reasoning among those with a higher level of formal education. Among those with poor hearing, hearing aid usage had a significant positive, but not necessarily causal, effect on both numerical and linguistic verbal reasoning (p < 0.005). The estimated effect of hearing aid usage was less than the effect of poor functional hearing. Structural equation modeling analyses confirmed that controlling for education reduced the effect of functional hearing on verbal reasoning and showed that controlling for executive function eliminated the effect. However, when computer usage was controlled for, the eliminating effect of executive function was weakened. Poor functional hearing was associated with poor verbal reasoning in a 40- to 70-year-old community-dwelling population after controlling for age, gender, and education. The effect of functional hearing on verbal reasoning was significantly reduced among hearing aid users and completely overcome by good executive function skills, which may be enhanced by playing computer games.

Risk for Femoral Fractures in Parkinson’s Disease Patients with and without Severe Functional Impairment

PubMed Central

Benzinger, Petra; Rapp, Kilian; Maetzler, Walter; König, Hans-Helmut; Jaensch, Andrea; Klenk, Jochen; Büchele, Gisela

2014-01-01

Background Impaired balance is a major problem in patients with idiopathic Parkinson’s disease (PD) resulting in an increased risk of falls and fall-related fractures. Most studies which analyzed the risk of femoral fractures in patients with idiopathic PD were performed either in specialized centers or excluded very frail patients. The current study used a large population-based dataset in order to analyze the risk of femoral fractures in patients with idiopathic PD. Methods Data from more than 880.000 individuals aged 65 years or older and insured between 2004 and 2009 at a large German health insurance company were used for the analyses. Persons with idiopathic PD were identified by the dispensing of Parkinson-specific medication and by hospital diagnoses, if available. People without PD served as the reference group. Incident femoral fractures were obtained from hospital diagnoses. Analyses were stratified by gender and information on severe functional impairment (care need) as provided by reimbursement claims. Results Compared with the reference group, persons with idiopathic PD had a more than doubled risk to sustain a femoral fracture. The risk was higher in men (HR = 2.61; 95%-CI: 2.28–2.98) than in women (HR = 1.79; 95%-CI: 1.66–1.94). The increased risk was only observed in people without severe functional impairment. The sensitivity analysis using a refined definition of idiopathic PD patients yielded similar results. Conclusion The findings confirm the increased risk of femoral fractures in patients with idiopathic PD. The relative risk is particularly high in male PD patients and in patients without severe functional impairment. PMID:24853110

Associations between plasma tenofovir concentration and renal function markers in HIV-infected women.

PubMed

Mulubwa, Mwila; Rheeders, Malie; Fourie, Carla; Viljoen, Michelle

2016-01-01

Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubular dysfunction and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART). These markers were also compared to a HIV-uninfected control group. HIV-infected women ( n = 30) on TDF-based ART were matched with 30 controls for age and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Stepwise regression, Mann-Whitney test, unpaired and paired t -tests were applied in the statistical analyses. TFV concentration was independently associated with albuminuria (adjusted r 2 = 0.339 ; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR ( p = 0.038), CrCl ( p = 0.032) and albuminuria ( p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR ( p < 0.001) and CrCl ( p = 0.008) increased from baseline to follow-up in HIV-infected women. Plasma TFV concentration was associated with increased albuminuria in HIV-infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

The Landscape of Circular RNA Expression Profiles in Papillary Thyroid Carcinoma Based on RNA Sequencing.

PubMed

Lan, Xiabin; Xu, Jiajie; Chen, Chao; Zheng, Chuanming; Wang, Jiafeng; Cao, Jun; Zhu, Xuhang; Ge, Minghua

2018-05-25

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. However, the molecular mechanisms responsible for its tumorigenesis and progression remain largely unknown. Circular RNA (circRNA) is a novel type of noncoding RNA that can serve as an ideal biomarker due to its stability. Recent evidence suggests that circRNAs play important roles in tumorigenesis. This study aims to investigate circRNA expression profiles and their potential biological functions in PTC. High-throughput RNA sequencing was used to assess circRNA expression profiles in PTC, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate dysregulated circRNAs. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic value of circRNAs for PTC. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were employed to determine the biological functions of differentially expressed circRNAs. Bioinformatic analyses were applied to predict interactions between circRNAs and microRNAs (miRNAs), and a circRNA-miRNA-mRNA network was constructed using Cytoscape software. We identified a number of differentially expressed circRNAs in PTC tissues compared with paired normal thyroid tissues, with chr5: 160757890-160763776-, chr12: 40696591-40697936+, chr7: 22330794-22357656-, and chr21: 16386665-16415895- being upregulated, and chr7: 91924203-91957214+, chr2: 179514891-179516047-, chr9: 16435553-16437522-, and chr22: 36006931-36007153- being downregulated. These findings were confirmed by qRT-PCR, and ROC curves indicated that they can serve as potential biomarkers for PTC. GO and KEGG pathway analyses showed that some of these circRNAs are related to cancers. Additionally, bioinformatic analyses revealed a potential competing-endogenous-RNA-regulating network among circRNAs, miRNAs, and mRNAs. Our study results depict the landscape of circRNA expression profiles in PTC and also provide potential biomarkers for PTC. Further functional and mechanistic studies of these circRNAs may improve our understanding of PTC tumorigenesis. © 2018 The Author(s). Published by S. Karger AG, Basel.

Genome-wide analysis of the TPX2 family proteins in Eucalyptus grandis.

PubMed

Du, Pingzhou; Kumar, Manoj; Yao, Yuan; Xie, Qiaoli; Wang, Jinyan; Zhang, Baolong; Gan, Siming; Wang, Yuqi; Wu, Ai-Min

2016-11-24

The Xklp2 (TPX2) proteins belong to the microtubule-associated (MAP) family of proteins. All members of the family contain the conserved TPX2 motif, which can interact with microtubules, regulate microtubule dynamics or assist with different microtubule functions, for example, maintenance of cell morphology or regulation of cell growth and development. However, the role of members of the TPX family have not been studied in the model tree species Eucalyptus to date. Here, we report the identification of the members of the TPX2 family in Eucalyptus grandis (Eg) and analyse the expression patterns and functions of these genes. In present study, a comprehensive analysis of the plant TPX2 family proteins was performed. Phylogenetic analyses indicated that the genes can be classified into 6 distinct subfamilies. A genome-wide survey identified 12 members of the TPX2 family in the sequenced genome of Eucalyptus grandis. The basic genetic properties of the TPX2 family in Eucalyptus were analysed. Our results suggest that the TPX2 family proteins within different sub-groups are relatively conserved but there are important differences between groups. Quantitative real-time PCR (qRT-PCR) was performed to confirm the expression levels of the genes in different tissues. The results showed that in the whole plant, the levels of EgWDL5 transcript are the highest, followed by those of EgWDL4. Compared with other tissues, the level of the EgMAP20 transcript is the highest in the root. Over-expression of EgMAP20 in Arabidopsis resulted in organ twisting. The cotyledon petioles showed left-handed twisting while the hypocotyl epidermal cells produced right-handed helical twisting. Finally, EgMAP20, EgWDL3 and EgWDL3L were all able to decorate microtubules. Plant TPX2 family proteins were systematically analysed using bioinformatics methods. There are 12 TPX2 family proteins in Eucalyptus. We have performed an initial characterization of the functions of several members of the TPX2 family. We found that the gene products are localized to the microtubule cytoskeleton. Our results lay the foundation for future efforts to reveal the biological significance of TPX2 family proteins in Eucalyptus.

The applicability of a weight loss grading system in cancer cachexia: a longitudinal analysis.

PubMed

Vagnildhaug, Ola Magne; Blum, David; Wilcock, Andrew; Fayers, Peter; Strasser, Florian; Baracos, Vickie E; Hjermstad, Marianne J; Kaasa, Stein; Laird, Barry; Solheim, Tora S

2017-10-01

A body mass index (BMI) adjusted weight loss grading system (WLGS) is related to survival in patients with cancer. The aim of this study was to examine the applicability of the WLGS by confirming its prognostic validity, evaluating its relationship to cachexia domains, and exploring its ability to predict cachexia progression. An international, prospective observational study of patients with incurable cancer was conducted. For each patient, weight loss grade was scored 0-4. Weight loss grade 0 represents a high BMI with limited weight loss, progressing through to weight loss grade 4 representing low BMI and a high degree of weight loss. Survival analyses were used to confirm prognostic validity. Analyses of variance were used to evaluate the relationship between the WLGS and cachexia domains [anorexia, dietary intake, Karnofsky performance status (KPS), and physical and emotional functioning]. Cox regression was used to evaluate if the addition of cachexia domains to the WLGS improved prognostic accuracy. Predictive ability of cachexia progression was assessed by estimating proportion of patients progressing to a more advanced weight loss grade. One thousand four hundred six patients were analysed (median age 66 years; 50% female, 63% KPS ≤ 70). The overall effect of the WLGS on survival was significant as expressed by change in -2 log likelihood (P < 0.001) and persisted after adjustment for age, sex, and cancer type and stage (P < 0.001). Median survival decreased across the weight loss grades ranging from 407 days (95% CI 312-502)-weight loss grade 0 to 119 days (95% CI 93-145)-weight loss grade 4. All cachexia domains significantly deteriorated with increasing weight loss grade, and deterioration was greatest for dietary intake, with a difference corresponding to 0.87 standard deviations between weight loss grades 0 and 4. The addition of KPS, anorexia, and physical and emotional functioning improved the prognostic accuracy of the WLGS. Likelihood of cachexia progression was greater in patients with weight loss grade 2 (39%) than that with weight loss grade 0 (19%) or 1 (22%). The WLGS is related to survival, cachexia domains, and the likelihood of progression. Adding certain cachexia domains to the WLGS improves prognostic accuracy. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Growth, structural, optical and thermal properties of gamma-glycine crystal.

PubMed

Balakrishnan, T; Babu, R Ramesh; Ramamurthi, K

2008-04-01

Single crystals of gamma-glycine were grown from a mixture of glycine, water and lithium bromide. Single crystal X-ray diffraction analysis confirmed the growth of gamma-glycine phase. Presence of various functional groups of gamma-glycine was identified by FTIR spectrum. Optical absorbance spectrum recorded in the wavelength range of UV-vis-NIR revealed that this crystal has good optical transparency in the range 250-1500 nm. Vickers microhardness values were estimated on the prominent (100) face. Thermogravimetric and differential scanning calorimetric analyses were carried out to study the thermal properties of gamma-glycine. Second harmonic generation efficiency of the crystal measured by Kurtz's powder method using Nd:YAG laser is about three times that of KDP.

Growth, structural, spectral, optical, and thermal studies on amino acid based new NLO single crystal: L-phenylalanine-4-nitrophenol.

PubMed

Prakash, M; Lydia Caroline, M; Geetha, D

2013-05-01

A new organic nonlinear optical single crystal, L-phenylalanine-4-nitrophenol (LPAPN) belonging to the amino acid group has been successfully grown by slow evaporation technique. The lattice parameters of the grown crystal have been determined by X-ray diffraction studies. FT-IR spectrum was recorded to identify the presence of functional group and molecular structure was confirmed by NMR spectrum. Thermal strength of the grown crystal has been studied using TG-DTA analyses. The grown crystals were found to be transparent in the entire visible region. The existence of second harmonic generation signals was observed using Nd:YAG laser with fundamental wavelength of 1064 nm. Copyright © 2013 Elsevier B.V. All rights reserved.

Echinostoma caproni: identification of enolase in excretory/secretory products, molecular cloning, and functional expression.

PubMed

Marcilla, Antonio; Pérez-García, Ana; Espert, Ana; Bernal, Dolores; Muñoz-Antolí, Carla; Esteban, José Guillermo; Toledo, Rafael

2007-09-01

In order to investigate molecules that could be involved in host-trematode relationships, we have analysed the excretory/secretory products (ESP) of Echinostoma caproni following a proteomic approach. Actin, Gluthathione S-transferase (GST) and enolase have been identified in the ESP. Enolase, observed to be one of the most abundant proteins, was further characterized. The molecular cloning and in vitro expression in Escherichia coli of E. caproni enolase allowed us to determine that the protein contains 431 amino acids and a theoretical MW of 46272 Da. E. caproni enolase shows high homology to other trematode enolases. The recombinant protein binds specifically to human plasminogen in vitro, as observed for the native protein, confirming its properties as a host-interacting molecule.

Neural network classification of clinical neurophysiological data for acute care monitoring

NASA Technical Reports Server (NTRS)

Sgro, Joseph

1994-01-01

The purpose of neurophysiological monitoring of the 'acute care' patient is to allow the accurate recognition of changing or deteriorating neurological function as close to the moment of occurrence as possible, thus permitting immediate intervention. Results confirm that: (1) neural networks are able to accurately identify electroencephalogram (EEG) patterns and evoked potential (EP) wave components, and measuring EP waveform latencies and amplitudes; (2) neural networks are able to accurately detect EP and EEG recordings that have been contaminated by noise; (3) the best performance was obtained consistently with the back propagation network for EP and the HONN for EEG's; (4) neural network performed consistently better than other methods evaluated; and (5) neural network EEG and EP analyses are readily performed on multichannel data.

The impact of religiosity and individual prayer activities on advanced cancer patients' health: is there any difference in function of whether or not receiving palliative anti-neoplastic therapy?

PubMed

Paiva, Carlos Eduardo; Paiva, Bianca Sakamoto Ribeiro; Yennurajalingam, Sriram; Hui, David

2014-12-01

Consecutive patients (n = 221) presenting for initial consultation at a palliative care outpatient clinic were prospectively interviewed and then followed until death. Individual prayer activity (IPA) and global religion scores were associated with quality of life, symptoms, inflammatory markers, and survival. Analyses were adjusted for whether patients were still receiving anti-neoplastic therapies (ANTs) or not. Higher religion scores were associated with lower levels of inflammation in advanced cancer patients still undergoing ANTs. Additionally, higher IPA was an independent good prognostic factor in patients on active ANTs. Further studies are necessary to confirm these findings and to investigate possible biological mechanisms involved.

Analytic theory of photoacoustic wave generation from a spheroidal droplet.

PubMed

Li, Yong; Fang, Hui; Min, Changjun; Yuan, Xiaocong

2014-08-25

In this paper, we develop an analytic theory for describing the photoacoustic wave generation from a spheroidal droplet and derive the first complete analytic solution. Our derivation is based on solving the photoacoustic Helmholtz equation in spheroidal coordinates with the separation-of-variables method. As the verification, besides carrying out the asymptotic analyses which recover the standard solutions for a sphere, an infinite cylinder and an infinite layer, we also confirm that the partial transmission and reflection model previously demonstrated for these three geometries still stands. We expect that this analytic solution will find broad practical uses in interpreting experiment results, considering that its building blocks, the spheroidal wave functions (SWFs), can be numerically calculated by the existing computer programs.

Standardized Symptom Measurement of Individuals with Early Lyme Disease Over Time.

PubMed

Bechtold, Kathleen T; Rebman, Alison W; Crowder, Lauren A; Johnson-Greene, Doug; Aucott, John N

2017-03-01

Understanding the Lyme disease (LD) literature is challenging given the lack of consistent methodology and standardized measurement of symptoms and the impact on functioning. This prospective study incorporates well-validated measures to capture the symptom picture of individuals with early LD from time of diagnosis through 6-months post-treatment. One hundred seven patients with confirmed early LD and 26 healthy controls were evaluated using standardized instruments for pain, fatigue, depressive symptoms, functional impact, and cognitive functioning. Prior to antibiotic treatment, patients experience notable symptoms of fatigue and pain statistically higher than controls. After treatment, there are no group differences, suggesting that symptoms resolve and that there are no residual cognitive impairments at the level of group analysis. However, using subgroup analyses, some individuals experience persistent symptoms that lead to functional decline and these individuals can be identified immediately post-completion of standard antibiotic treatment using well-validated symptom measures. Overall, the findings suggest that ideally-treated early LD patients recover well and experience symptom resolution over time, though a small subgroup continue to suffer with symptoms that lead to functional decline. The authors discuss use of standardized instruments for identification of individuals who warrant further clinical follow-up. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

Implementation of the AES as a Hash Function for Confirming the Identity of Software on a Computer System

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

Hansen, Randy R.; Bass, Robert B.; Kouzes, Richard T.

2003-01-20

This paper provides a brief overview of the implementation of the Advanced Encryption Standard (AES) as a hash function for confirming the identity of software resident on a computer system. The PNNL Software Authentication team chose to use a hash function to confirm software identity on a system for situations where: (1) there is limited time to perform the confirmation and (2) access to the system is restricted to keyboard or thumbwheel input and output can only be displayed on a monitor. PNNL reviewed three popular algorithms: the Secure Hash Algorithm - 1 (SHA-1), the Message Digest - 5 (MD-5),more » and the Advanced Encryption Standard (AES) and selected the AES to incorporate in software confirmation tool we developed. This paper gives a brief overview of the SHA-1, MD-5, and the AES and sites references for further detail. It then explains the overall processing steps of the AES to reduce a large amount of generic data-the plain text, such is present in memory and other data storage media in a computer system, to a small amount of data-the hash digest, which is a mathematically unique representation or signature of the former that could be displayed on a computer's monitor. This paper starts with a simple definition and example to illustrate the use of a hash function. It concludes with a description of how the software confirmation tool uses the hash function to confirm the identity of software on a computer system.« less

Confirming criticality safety of TRU waste with neutron measurements and risk analyses

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

Winn, W.G.; Hochel, R.D.

1992-04-01

The criticality safety of {sup 239}Pu in 55-gallon drums stored in TRU waste containers (culverts) is confirmed using NDA neutron measurements and risk analyses. The neutron measurements yield a {sup 239}Pu mass and k{sub eff} for a culvert, which contains up to 14 drums. Conservative probabilistic risk analyses were developed for both drums and culverts. Overall {sup 239}Pu mass estimates are less than a calculated safety limit of 2800 g per culvert. The largest measured k{sub eff} is 0.904. The largest probability for a critical drum is 6.9 {times} 10{sup {minus}8} and that for a culvert is 1.72 {times} 10{supmore » {minus}7}. All examined suspect culverts, totaling 118 in number, are appraised as safe based on these observations.« less

Facile and highly efficient approach for the fabrication of multifunctional silk nanofibers containing hydroxyapatite and silver nanoparticles.

PubMed

Sheikh, Faheem A; Ju, Hyung Woo; Moon, Bo Mi; Park, Hyun Jung; Kim, Jung-Ho; Lee, Ok Joo; Park, Chan Hum

2014-10-01

In this study, a good combination consisting of electrospun silk fibroin nanofibers incorporated with high-purity hydroxyapatite (HAp) nanoparticles (NPs) and silver NPs is introduced as antimicrobial for tissue engineering applications. The variable pressure field emission scanning electron microscope results confirmed randomly placed nanofibers are produced with highly dispersed HAp and silver NPs in nanofibers after electrospinning. The X-ray diffraction results demonstrated crystalline features of each of the three components used for electrospinning. Moreover, the TEM-EDS analysis confirmed the presence and chemical nature of each component over individual silk nanofiber. The FT-IR analyses was used confirm the different vibration modes caused due to functional groups present in silk fibroin, Hap, and silver NPs. The obtained nanofibers were checked for antimicrobial activity by using two model organisms Escherichia coli and Staphylococcus aureus. Subsequently, the antimicrobial tests have indicated that prepared nanofibers do possess good bactericidal activity. The ability of N,N-dimethylformamide and silk fibroin used to reduce silver nitrate into silver metal was evaluated using MTT assay. The nanofibers were grown in presence of NIH 3T3 fibroblasts, which revealed toxic behavior to fibroblasts at higher concentrations of silver nitrate used in this study. Furthermore, cell attachment studies on nanofibers for 3 and 12 days of incubation time were minutely observed and correlated with the results of MTT assay. The reported results confirmed the high amounts of silver nitrate can lead to toxic effects on viability of fibroblasts and had bad effect in cell attachment. © 2013 Wiley Periodicals, Inc.

Supply Chain Collaboration: Information Sharing in a Tactical Operating Environment

DTIC Science & Technology

2013-06-01

architecture, there are four tiers: Client (Web Application Clients ), Presentation (Web-Server), Processing (Application-Server), Data (Database...organization in each period. This data will be collected to analyze. i) Analyses and Validation: We will do a statistics test in this data, Pareto ...notes, outstanding deliveries, and inventory. i) Analyses and Validation: We will do a statistics test in this data, Pareto analyses and confirmation

Emergency School Aid Act (ESAA) Evaluation: Results of Supplemental Analyses Conducted in the Contract Extension Period.

ERIC Educational Resources Information Center

Carriere, Ronald A.; And Others

This report focuses on a set of supplemental analyses that were performed on portions of the Emergency School Aid Act (ESAA) evaluation data. The goal of these analyses was to explore additional relationships in the data that might help to inform program policy, to confirm and/or further explicate some of the findings reported earlier, and to put…

Synthesis, nucleation, growth, structural, spectral, thermal, linear and nonlinear optical studies of novel organic NLO crystal: 4-fluoro 4-nitrostilbene (FONS).

PubMed

Dinakaran, Paul M; Kalainathan, S

2013-03-15

A novel organic nonlinear optical material 4-fluoro 4-nitrostilbene (FONS), with molecular formula (C(14)H(10)FNO(2)) has been synthesized. Using ethyl methyl ketone as solvent, the synthesized material has been repeatedly recrystallized to minimize the impurities and good optical quality single crystals were harvested by slow evaporation method. Single crystal X-ray diffraction analysis reveals that the grown FONS crystal belongs to monoclinic system with noncentrosymmetric space group "P2(1)". The powder X-ray diffraction pattern of FONS has been recorded. Functional groups of the title compound were confirmed by FTIR and the molecular structure was confirmed by (1)HNMR. The UV-vis-NIR absorption study reveals no absorption in the visible region and the cut-off wavelength was found to be at 408 nm. Optical band gap (E(g)) of the grown crystal was found to be 3.27 eV and also the optical constants were determined. Thermal behaviour of the FONS has been studied by TGA/DTA analyses. From the mass spectrum, the ratio of compound formation of FONS was analyzed. The NLO property has been confirmed by Kurtz and Perry powder SHG technique and the SHG efficiency of FONS (262 mV) crystal was found to be 12 times greater than that of KDP (21.7 mV). Copyright © 2013 Elsevier B.V. All rights reserved.

Cyclic Nanostructures of Tungsten Oxide (WO3) n   (n = 2-6) as NO x Gas Sensor: A Theoretical Study.

PubMed

Izadyar, Mohammad; Jamsaz, Azam

2014-01-01

Today's WO3-based gas sensors have received a lot of attention, because of important role as a sensitive layer for detection of the small quantities of  NO x . In this research, a theoretical study has been done on the sensing properties of different cyclic nanoclusters of (WO3) n   (n = 2-6) for NO x   (x = 1,2) gases. Based on the calculated adsorption energies by B3LYP and X3LYP functionals, from the different orientations of  NO x molecule on the tungsten oxide clusters, O-N⋯W was preferred. Different sizes of the mentioned clusters have been analyzed and W2O6 cluster was chosen as the best candidate for NO x detection from the energy viewpoint. Using the concepts of the chemical hardness and electronic charge transfer, some correlations between the energy of adsorption and interaction energy have been established. These analyses confirmed that the adsorption energy will be boosted with charge transfer enhancement. However, the chemical hardness relationship is reversed. Finally, obtained results from the natural bond orbital and electronic density of states analysis confirmed the electronic charge transfer from the adsorbates to WO3 clusters and Fermi level shifting after adsorption, respectively. The last parameter confirms that the cyclic clusters of tungsten oxide can be used as NO x gas sensors.

Cyclic Nanostructures of Tungsten Oxide (WO3)n  (n = 2–6) as NOx Gas Sensor: A Theoretical Study

PubMed Central

Izadyar, Mohammad; Jamsaz, Azam

2014-01-01

Today's WO3-based gas sensors have received a lot of attention, because of important role as a sensitive layer for detection of the small quantities of  NOx. In this research, a theoretical study has been done on the sensing properties of different cyclic nanoclusters of (WO3)n  (n = 2–6) for NOx  (x = 1,2) gases. Based on the calculated adsorption energies by B3LYP and X3LYP functionals, from the different orientations of  NOx molecule on the tungsten oxide clusters, O–N⋯W was preferred. Different sizes of the mentioned clusters have been analyzed and W2O6 cluster was chosen as the best candidate for NOx detection from the energy viewpoint. Using the concepts of the chemical hardness and electronic charge transfer, some correlations between the energy of adsorption and interaction energy have been established. These analyses confirmed that the adsorption energy will be boosted with charge transfer enhancement. However, the chemical hardness relationship is reversed. Finally, obtained results from the natural bond orbital and electronic density of states analysis confirmed the electronic charge transfer from the adsorbates to WO3 clusters and Fermi level shifting after adsorption, respectively. The last parameter confirms that the cyclic clusters of tungsten oxide can be used as NOx gas sensors. PMID:25544841

Informing the Symptom Profile of Complicated Grief

PubMed Central

Simon, Naomi M.; Wall, Melanie M.; Keshaviah, Aparna; Dryman, M. Taylor; LeBlanc, Nicole J.; Shear, M. Katherine

2010-01-01

Background Complicated Grief (CG) is under consideration as a new diagnosis in DSM5. We sought to add empirical support to the current dialogue by examining the commonly used Inventory of Complicated Grief (ICG) scale completed by 782 bereaved individuals. Methods We employed IRT analyses, factor analyses, and sensitivity and specificity analyses utilizing our full sample (n=782), and also compared confirmed CG cases (n=288) to non-cases (n=377). Confirmed CG cases were defined as individuals bereaved at least 6 months who were seeking care for CG, had an ICG ≥ 30, and received a structured clinical interview for CG by a certified clinician confirming CG as their primary illness. Non-cases were bereaved individuals who did not present with CG as a primary complaint (including those with depression, bipolar disorder, anxiety disorders and controls) and had an ICG<25. Results IRT analyses provided guidance about the most informative individual items and their association with CG severity. Factor analyses demonstrated a single factor solution when the full sample was considered, but within CG cases, six symptom clusters emerged: 1) yearning and preoccupation with the deceased, 2) anger and bitterness, 3) shock and disbelief, 4) estrangement from others, 5) hallucinations of the deceased, and 6) behavior change, including avoidance and proximity seeking. The presence of at least one symptom from three different symptom clusters optimized sensitivity (94.8%) and specificity (98.1%). Conclusions These data, derived from a diverse and predominantly clinical help seeking population, add an important perspective to existing suggestions for DSM5 criteria for CG. PMID:21284064

β1-adrenergic receptor stimulation by agonist Compound 49b restores insulin receptor signal transduction in vivo

PubMed Central

Jiang, Youde; Zhang, Qiuhua; Ye, Eun-Ah

2014-01-01

Purpose Determine whether Compound 49b treatment ameliorates retinal changes due to the lack of β2-adrenergic receptor signaling. Methods Using retinas from 3-month-old β2-adrenergic receptor-deficient mice, we treated mice with our novel β1-/β2-adrenergic receptor agonist, Compound 49b, to assess the effects of adrenergic agonists acting only on β1-adrenergic receptors due to the absence of β2-adrenergic receptors. Western blotting or enzyme-linked immunosorbent assay (ELISA) analyses were performed for β1- and β2-adrenergic receptors, as well as key insulin resistance proteins, including TNF-α, SOCS3, IRS-1Ser307, and IRTyr960. Analyses were also performed on key anti- and proapoptotic proteins: Akt, Bcl-xL, Bax, and caspase 3. Electroretinogram analyses were conducted to assess functional changes, while histological assessment was conducted for changes in retinal thickness. Results A 2-month treatment of β2-adrenergic receptor-deficient mice with daily eye drops of 1 mM Compound 49b, a novel β1- and β2-adrenergic receptor agonist, reversed the changes in insulin resistance markers (TNF-α and SOCS3) observed in untreated β2-adrenergic receptor-deficient mice, and concomitantly increased morphological integrity (retinal thickness) and functional responses (electroretinogram amplitude). These results suggest that stimulating β1-adrenergic receptors on retinal endothelial cells or Müller cells can compensate for the loss of β2-adrenergic receptor signaling on Müller cells, restore insulin signal transduction, reduce retinal apoptosis, and enhance retinal function. Conclusions Since our previous studies with β1-adrenergic receptor knockout mice confirmed that the reverse also occurs (β2-adrenergic receptor stimulation can compensate for the loss of β1-adrenergic receptor activity), it appears that increased activity in either of these pathways alone is sufficient to block insulin resistance–based retinal cell apoptosis. PMID:24966659

Comparative and Joint Analysis of Two Metagenomic Datasets from a Biogas Fermenter Obtained by 454-Pyrosequencing

PubMed Central

Jaenicke, Sebastian; Ander, Christina; Bekel, Thomas; Bisdorf, Regina; Dröge, Marcus; Gartemann, Karl-Heinz; Jünemann, Sebastian; Kaiser, Olaf; Krause, Lutz; Tille, Felix; Zakrzewski, Martha; Pühler, Alfred

2011-01-01

Biogas production from renewable resources is attracting increased attention as an alternative energy source due to the limited availability of traditional fossil fuels. Many countries are promoting the use of alternative energy sources for sustainable energy production. In this study, a metagenome from a production-scale biogas fermenter was analysed employing Roche's GS FLX Titanium technology and compared to a previous dataset obtained from the same community DNA sample that was sequenced on the GS FLX platform. Taxonomic profiling based on 16S rRNA-specific sequences and an Environmental Gene Tag (EGT) analysis employing CARMA demonstrated that both approaches benefit from the longer read lengths obtained on the Titanium platform. Results confirmed Clostridia as the most prevalent taxonomic class, whereas species of the order Methanomicrobiales are dominant among methanogenic Archaea. However, the analyses also identified additional taxa that were missed by the previous study, including members of the genera Streptococcus, Acetivibrio, Garciella, Tissierella, and Gelria, which might also play a role in the fermentation process leading to the formation of methane. Taking advantage of the CARMA feature to correlate taxonomic information of sequences with their assigned functions, it appeared that Firmicutes, followed by Bacteroidetes and Proteobacteria, dominate within the functional context of polysaccharide degradation whereas Methanomicrobiales represent the most abundant taxonomic group responsible for methane production. Clostridia is the most important class involved in the reductive CoA pathway (Wood-Ljungdahl pathway) that is characteristic for acetogenesis. Based on binning of 16S rRNA-specific sequences allocated to the dominant genus Methanoculleus, it could be shown that this genus is represented by several different species. Phylogenetic analysis of these sequences placed them in close proximity to the hydrogenotrophic methanogen Methanoculleus bourgensis. While rarefaction analyses still indicate incomplete coverage, examination of the GS FLX Titanium dataset resulted in the identification of additional genera and functional elements, providing a far more complete coverage of the community involved in anaerobic fermentative pathways leading to methane formation. PMID:21297863

Pancreatic cancer cell lines as patient-derived avatars: genetic characterisation and functional utility.

PubMed

Knudsen, Erik S; Balaji, Uthra; Mannakee, Brian; Vail, Paris; Eslinger, Cody; Moxom, Christopher; Mansour, John; Witkiewicz, Agnieszka K

2018-03-01

Pancreatic ductal adenocarcinoma (PDAC) is a therapy recalcitrant disease with the worst survival rate of common solid tumours. Preclinical models that accurately reflect the genetic and biological diversity of PDAC will be important for delineating features of tumour biology and therapeutic vulnerabilities. 27 primary PDAC tumours were employed for genetic analysis and development of tumour models. Tumour tissue was used for derivation of xenografts and cell lines. Exome sequencing was performed on the originating tumour and developed models. RNA sequencing, histological and functional analyses were employed to determine the relationship of the patient-derived models to clinical presentation of PDAC. The cohort employed captured the genetic diversity of PDAC. From most cases, both cell lines and xenograft models were developed. Exome sequencing confirmed preservation of the primary tumour mutations in developed cell lines, which remained stable with extended passaging. The level of genetic conservation in the cell lines was comparable to that observed with patient-derived xenograft (PDX) models. Unlike historically established PDAC cancer cell lines, patient-derived models recapitulated the histological architecture of the primary tumour and exhibited metastatic spread similar to that observed clinically. Detailed genetic analyses of tumours and derived models revealed features of ex vivo evolution and the clonal architecture of PDAC. Functional analysis was used to elucidate therapeutic vulnerabilities of relevance to treatment of PDAC. These data illustrate that with the appropriate methods it is possible to develop cell lines that maintain genetic features of PDAC. Such models serve as important substrates for analysing the significance of genetic variants and create a unique biorepository of annotated cell lines and xenografts that were established simultaneously from same primary tumour. These models can be used to infer genetic and empirically determined therapeutic sensitivities that would be germane to the patient. 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/.

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.

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.

Future of Mechatronics and Human

NASA Astrophysics Data System (ADS)

Harashima, Fumio; Suzuki, Satoshi

This paper mentions circumstance of mechatronics that sustain our human society, and introduces HAM(Human Adaptive Mechatronics)-project as one of research projects to create new human-machine system. The key point of HAM is skill, and analysis of skill and establishment of assist method to enhance total performance of human-machine system are main research concerns. As study of skill is an elucidation of human itself, analyses of human higher function are significant. In this paper, after surveying researches of human brain functions, an experimental analysis of human characteristic in machine operation is shown as one example of our research activities. We used hovercraft simulator as verification system including observation, voluntary motion control and machine operation that are needed to general machine operation. Process and factors to become skilled were investigated by identification of human control characteristics with measurement of the operator's line-of sight. It was confirmed that early switching of sub-controllers / reference signals in human and enhancement of space perception are significant.

Genome-wide analysis of TCP family in tobacco.

PubMed

Chen, L; Chen, Y Q; Ding, A M; Chen, H; Xia, F; Wang, W F; Sun, Y H

2016-05-23

The TCP family is a transcription factor family, members of which are extensively involved in plant growth and development as well as in signal transduction in the response against many physiological and biochemical stimuli. In the present study, 61 TCP genes were identified in tobacco (Nicotiana tabacum) genome. Bioinformatic methods were employed for predicting and analyzing the gene structure, gene expression, phylogenetic analysis, and conserved domains of TCP proteins in tobacco. The 61 NtTCP genes were divided into three diverse groups, based on the division of TCP genes in tomato and Arabidopsis, and the results of the conserved domain and sequence analyses further confirmed the classification of the NtTCP genes. The expression pattern of NtTCP also demonstrated that majority of these genes play important roles in all the tissues, while some special genes exercise their functions only in specific tissues. In brief, the comprehensive and thorough study of the TCP family in other plants provides sufficient resources for studying the structure and functions of TCPs in tobacco.

The asymptotic behaviour of parton distributions at small and large x.

PubMed

Ball, Richard D; Nocera, Emanuele R; Rojo, Juan

2016-01-01

It has been argued from the earliest days of quantum chromodynamics that at asymptotically small values of x the parton distribution functions (PDFs) of the proton behave as [Formula: see text], where the values of [Formula: see text] can be deduced from Regge theory, while at asymptotically large values of x the PDFs behave as [Formula: see text], where the values of [Formula: see text] can be deduced from the Brodsky-Farrar quark counting rules. We critically examine these claims by extracting the exponents [Formula: see text] and [Formula: see text] from various global fits of parton distributions, analysing their scale dependence, and comparing their values to the naive expectations. We find that for valence distributions both Regge theory and counting rules are confirmed, at least within uncertainties, while for sea quarks and gluons the results are less conclusive. We also compare results from various PDF fits for the structure function ratio [Formula: see text] at large x , and caution against unrealistic uncertainty estimates due to overconstrained parametrisations.

Effect of Knee Orthoses on Hamstring Contracture in Children With Cerebral Palsy: Multiple Single-Subject Study.

PubMed

Laessker-Alkema, Kristina; Eek, Meta Nyström

2016-01-01

To examine the effect of knee orthoses on extensibility of the hamstrings in children with spastic cerebral palsy (CP). The short-term effects of knee orthoses on passive range of motion (ROM), spasticity, and gross motor function of the hamstrings. Ten children with spastic CP, aged 5 to 14 years, at Gross Motor Function Classification System levels I to V, were followed. The orthoses were worn for a minimum of 30 minutes day, 5 days per week, during the intervention period of 8 weeks. Visual analysis using the Two Standard Deviation Band Method supported improvements in passive ROM for all 20 hamstring muscles and in 12 of 14 knee extension measurements. Analyses with the Wilcoxon signed rank test confirm the individual results and support a significant increase in hamstring muscles (P = .005) and knee extension (right: P =.028; left: P =.018) compared with baseline. In children with spastic CP, 8 weeks of treatment with knee orthoses can improve extensibility of the hamstrings.

SIRT1 decreases Lox-1-mediated foam cell formation in atherogenesis

PubMed Central

Stein, Sokrates; Lohmann, Christine; Schäfer, Nicola; Hofmann, Janin; Rohrer, Lucia; Besler, Christian; Rothgiesser, Karin M.; Becher, Burkhard; Hottiger, Michael O.; Borén, Jan; McBurney, Michael W.; Landmesser, Ulf; Lüscher, Thomas F.; Matter, Christian M.

2010-01-01

Aims Endothelial activation, macrophage infiltration, and foam cell formation are pivotal steps in atherogenesis. Our aim in this study was to analyse the role of SIRT1, a class III deacetylase with important metabolic functions, in plaque macrophages and atherogenesis. Methods and results Using partial SIRT1 deletion in atherosclerotic mice, we demonstrate that SIRT1 protects against atherosclerosis by reducing macrophage foam cell formation. Peritoneal macrophages from heterozygous SIRT1 mice accumulate more oxidized low-density lipoprotein (oxLDL), thereby promoting foam cell formation. Bone marrow-restricted SIRT1 deletion confirmed that SIRT1 function in macrophages is sufficient to decrease atherogenesis. Moreover, we show that SIRT1 reduces the uptake of oxLDL by diminishing the expression of lectin-like oxLDL receptor-1 (Lox-1) via suppression of the NF-κB signalling pathway. Conclusion Our findings demonstrate protective effects of SIRT1 in atherogenesis and suggest pharmacological SIRT1 activation as a novel anti-atherosclerotic strategy by reducing macrophage foam cell formation. PMID:20418343

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

On the derivation of flow rating curves in data-scarce environments

NASA Astrophysics Data System (ADS)

Manfreda, Salvatore

2018-07-01

River monitoring is a critical issue for hydrological modelling that relies strongly on the use of flow rating curves (FRCs). In most cases, these functions are derived by least-squares fitting which usually leads to good performance indices, even when based on a limited range of data that especially lack high flow observations. In this context, cross-section geometry is a controlling factor which is not fully exploited in classical approaches. In fact, river discharge is obtained as the product of two factors: 1) the area of the wetted cross-section and 2) the cross-sectionally averaged velocity. Both factors can be expressed as a function of the river stage, defining a viable alternative in the derivation of FRCs. This makes it possible to exploit information about cross-section geometry limiting, at least partially, the uncertainty in the extrapolation of discharge at higher flow values. Numerical analyses and field data confirm the reliability of the proposed procedure for the derivation of FRCs.

Theoretical characterisation of point defects on a MoS2 monolayer by scanning tunnelling microscopy.

PubMed

González, C; Biel, B; Dappe, Y J

2016-03-11

Different S and Mo vacancies as well as their corresponding antisite defects in a free-standing MoS2 monolayer are analysed by means of scanning tunnelling microscopy (STM) simulations. Our theoretical methodology, based on the Keldysh nonequilibrium Green function formalism within the density functional theory (DFT) approach, is applied to simulate STM images for different voltages and tip heights. Combining the geometrical and electronic effects, all features of the different STM images can be explained, providing a valuable guide for future experiments. Our results confirm previous reports on S atom imaging, but also reveal a strong dependence on the applied bias for vacancies and antisite defects that include extra S atoms. By contrast, when additional Mo atoms cover the S vacancies, the MoS2 gap vanishes and a bias-independent bright protrusion is obtained in the STM image. Finally, we show that the inclusion of these point defects promotes the emergence of reactive dangling bonds that may act as efficient adsorption sites for external adsorbates.

Microarray Analysis of Differential Gene Expression Profile Between Human Fetal and Adult Heart.

PubMed

Geng, Zhimin; Wang, Jue; Pan, Lulu; Li, Ming; Zhang, Jitai; Cai, Xueli; Chu, Maoping

2017-04-01

Although many changes have been discovered during heart maturation, the genetic mechanisms involved in the changes between immature and mature myocardium have only been partially elucidated. Here, gene expression profile changed between the human fetal and adult heart was characterized. A human microarray was applied to define the gene expression signatures of the fetal (13-17 weeks of gestation, n = 4) and adult hearts (30-40 years old, n = 4). Gene ontology analyses, pathway analyses, gene set enrichment analyses, and signal transduction network were performed to predict the function of the differentially expressed genes. Ten mRNAs were confirmed by quantificational real-time polymerase chain reaction. 5547 mRNAs were found to be significantly differentially expressed. "Cell cycle" was the most enriched pathway in the down-regulated genes. EFGR, IGF1R, and ITGB1 play a central role in the regulation of heart development. EGFR, IGF1R, and FGFR2 were the core genes regulating cardiac cell proliferation. The quantificational real-time polymerase chain reaction results were concordant with the microarray data. Our data identified the transcriptional regulation of heart development in the second trimester and the potential regulators that play a prominent role in the regulation of heart development and cardiac cells proliferation.

Valorisation of chicken feathers: Characterisation of chemical properties.

PubMed

Tesfaye, Tamrat; Sithole, Bruce; Ramjugernath, Deresh; Chunilall, Viren

2017-10-01

The characterisation of the chemical properties of the whole chicken feather and its fractions (barb and rachis), was undertaken to identify opportunities for valorizing this waste product. The authors have described the physical, morphological, mechanical, electrical and thermal properties of the chicken feathers and related them to potential valorisation routes of the waste. However, identification of their chemical properties is necessary to complete a comprehensive description of chicken feather fractions. Hence, the chicken feathers were thoroughly characterised by proximate and ultimate analyses, elemental composition, spectroscopic analyses, durability in different solvents, burning test, and hydrophobicity. The proximate analysis of chicken feathers revealed the following compositions: crude lipid (0.83%), crude fibre (2.15%), crude protein (82.36%), ash (1.49%), NFE (1.02%) and moisture content (12.33%) whereas the ultimate analyses showed: carbon (64.47%), nitrogen (10.41%), oxygen (22.34%), and sulphur (2.64%). FTIR analysis revealed that the chicken feather fractions contain amide and carboxylic groups indicative of proteinious functional groups; XRD showed a crystallinity index of 22. Durability and burning tests confirmed that feathers behaved similarly to animal fibre. This reveals that chicken feather can be a valuable raw material in textile, plastic, cosmetics, pharmaceuticals, biomedical and bioenergy industries. Copyright © 2017 Elsevier Ltd. All rights reserved.

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder.

PubMed

Camargo Moreno, Maria; Mooney, Sandra M; Middleton, Frank A

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD.

Serum iron level and kidney function: a Mendelian randomization study.

PubMed

Del Greco M, Fabiola; Foco, Luisa; Pichler, Irene; Eller, Philipp; Eller, Kathrin; Benyamin, Beben; Whitfield, John B; Pramstaller, Peter P; Thompson, John R; Pattaro, Cristian; Minelli, Cosetta

2017-02-01

Iron depletion is a known consequence of chronic kidney disease (CKD), but there is contradicting epidemiological evidence on whether iron itself affects kidney function and whether its effect is protective or detrimental in the general population. While epidemiological studies tend to be affected by confounding and reverse causation, Mendelian randomization (MR) can provide unconfounded estimates of causal effects by using genes as instruments. We performed an MR study of the effect of serum iron levels on estimated glomerular filtration rate (eGFR), using genetic variants known to be associated with iron. MR estimates of the effect of iron on eGFR were derived based on the association of each variant with iron and eGFR from two large genome-wide meta-analyses on 48 978 and 74 354 individuals. We performed a similar MR analysis for ferritin, which measures iron stored in the body, using variants associated with ferritin. A combined MR estimate across all variants showed a 1.3% increase in eGFR per standard deviation increase in iron (95% confidence interval 0.4–2.1%; P = 0.004). The results for ferritin were consistent with those for iron. Secondary MR analyses of the effects of iron and ferritin on CKD did not show significant associations but had very low statistical power. Our study suggests a protective effect of iron on kidney function in the general population. Further research is required to confirm this causal association, investigate it in study populations at higher risk of CKD and explore its underlying mechanism of action.

A conserved RxLR effector interacts with host RABA-type GTPases to inhibit vesicle-mediated secretion of antimicrobial proteins.

PubMed

Tomczynska, Iga; Stumpe, Michael; Mauch, Felix

2018-04-19

Plant pathogens of the oomycete genus Phytophthora produce virulence factors, known as RxLR effector proteins that are transferred into host cells to suppress disease resistance. Here, we analyse the function of the highly conserved RxLR24 effector of Phytophthora brassicae. RxLR24 was expressed early in the interaction with Arabidopsis plants and ectopic expression in the host enhanced leaf colonization and zoosporangia formation. Co-immunoprecipitation (Co-IP) experiments followed by mass spectrometry identified different members of the RABA GTPase family as putative RxLR24 targets. Physical interaction of RxLR24 or its homologue from the potato pathogen Phytophthora infestans with different RABA GTPases of Arabidopsis or potato, respectively, was confirmed by reciprocal Co-IP. In line with the function of RABA GTPases in vesicular secretion, RxLR24 co-localized with RABA1a to vesicles and the plasma membrane. The effect of RxLR24 on the secretory process was analysed with fusion constructs of secreted antimicrobial proteins with a pH-sensitive GFP tag. PATHOGENESIS RELATED PROTEIN 1 (PR-1) and DEFENSIN (PDF1.2) were efficiently exported in control tissue, whereas in the presence of RxLR24 they both accumulated in the endoplasmic reticulum. Together our results imply a virulence function of RxLR24 effectors as inhibitors of RABA GTPase-mediated vesicular secretion of antimicrobial PR-1, PDF1.2 and possibly other defence-related compounds. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Isolation and analysis of membrane lipids and lipid rafts in common carp (Cyprinus carpio L.).

PubMed

Brogden, Graham; Propsting, Marcus; Adamek, Mikolaj; Naim, Hassan Y; Steinhagen, Dieter

2014-03-01

Cell membranes act as an interface between the interior of the cell and the exterior environment and facilitate a range of essential functions including cell signalling, cell structure, nutrient uptake and protection. It is composed of a lipid bilayer with integrated proteins, and the inner leaflet of the lipid bilayer comprises of liquid ordered (Lo) and liquid disordered (Ld) domains. Lo microdomains, also named as lipid rafts are enriched in cholesterol, sphingomyelin and certain types of proteins, which facilitate cell signalling and nutrient uptake. Lipid rafts have been extensively researched in mammals and the presence of functional lipid rafts was recently demonstrated in goldfish, but there is currently very little knowledge about their composition and function in fish. Therefore a protocol was established for the analysis of lipid rafts and membranous lipids in common carp (Cyprinus carpio L.) tissues. Twelve lipids were identified and analysed in the Ld domain of the membrane with the most predominant lipids found in all tissues being; triglycerides, cholesterol, phosphoethanolamine and phosphatidylcholine. Four lipids were identified in lipid rafts in all tissues analysed, triglycerides (33-62%) always found in the highest concentration followed by cholesterol (24-32%), phosphatidylcholine and sphingomyelin. Isolation of lipid rafts was confirmed by identifying the presence of the lipid raft associated protein flotillin, present at higher concentrations in the detergent resistant fraction. The data provided here build a lipid library of important carp tissues as a baseline for further studies into virus entry, protein trafficking or environmental stress analysis. Copyright © 2013 Elsevier Inc. All rights reserved.

Low nitrogen fertilization adapts rice root microbiome to low nutrient environment by changing biogeochemical functions.

PubMed

Ikeda, Seishi; Sasaki, Kazuhiro; Okubo, Takashi; Yamashita, Akifumu; Terasawa, Kimihiro; Bao, Zhihua; Liu, Dongyan; Watanabe, Takeshi; Murase, Jun; Asakawa, Susumu; Eda, Shima; Mitsui, Hisayuki; Sato, Tadashi; Minamisawa, Kiwamu

2014-01-01

Reduced fertilizer usage is one of the objectives of field management in the pursuit of sustainable agriculture. Here, we report on shifts of bacterial communities in paddy rice ecosystems with low (LN), standard (SN), and high (HN) levels of N fertilizer application (0, 30, and 300 kg N ha(-1), respectively). The LN field had received no N fertilizer for 5 years prior to the experiment. The LN and HN plants showed a 50% decrease and a 60% increase in biomass compared with the SN plant biomass, respectively. Analyses of 16S rRNA genes suggested shifts of bacterial communities between the LN and SN root microbiomes, which were statistically confirmed by metagenome analyses. The relative abundances of Burkholderia, Bradyrhizobium and Methylosinus were significantly increased in root microbiome of the LN field relative to the SN field. Conversely, the abundance of methanogenic archaea was reduced in the LN field relative to the SN field. The functional genes for methane oxidation (pmo and mmo) and plant association (acdS and iaaMH) were significantly abundant in the LN root microbiome. Quantitative PCR of pmoA/mcrA genes and a (13)C methane experiment provided evidence of more active methane oxidation in the rice roots of the LN field. In addition, functional genes for the metabolism of N, S, Fe, and aromatic compounds were more abundant in the LN root microbiome. These results suggest that low-N-fertilizer management is an important factor in shaping the microbial community structure containing key microbes for plant associations and biogeochemical processes in paddy rice ecosystems.

Genetic resources for maize cell wall biology.

PubMed

Penning, Bryan W; Hunter, Charles T; Tayengwa, Reuben; Eveland, Andrea L; Dugard, Christopher K; Olek, Anna T; Vermerris, Wilfred; Koch, Karen E; McCarty, Donald R; Davis, Mark F; Thomas, Steven R; McCann, Maureen C; Carpita, Nicholas C

2009-12-01

Grass species represent a major source of food, feed, and fiber crops and potential feedstocks for biofuel production. Most of the biomass is contributed by cell walls that are distinct in composition from all other flowering plants. Identifying cell wall-related genes and their functions underpins a fundamental understanding of growth and development in these species. Toward this goal, we are building a knowledge base of the maize (Zea mays) genes involved in cell wall biology, their expression profiles, and the phenotypic consequences of mutation. Over 750 maize genes were annotated and assembled into gene families predicted to function in cell wall biogenesis. Comparative genomics of maize, rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana) sequences reveal differences in gene family structure between grass species and a reference eudicot species. Analysis of transcript profile data for cell wall genes in developing maize ovaries revealed that expression within families differed by up to 100-fold. When transcriptional analyses of developing ovaries before pollination from Arabidopsis, rice, and maize were contrasted, distinct sets of cell wall genes were expressed in grasses. These differences in gene family structure and expression between Arabidopsis and the grasses underscore the requirement for a grass-specific genetic model for functional analyses. A UniformMu population proved to be an important resource in both forward- and reverse-genetics approaches to identify hundreds of mutants in cell wall genes. A forward screen of field-grown lines by near-infrared spectroscopic screen of mature leaves yielded several dozen lines with heritable spectroscopic phenotypes. Pyrolysis-molecular beam mass spectrometry confirmed that several nir mutants had altered carbohydrate-lignin compositions.

Low Nitrogen Fertilization Adapts Rice Root Microbiome to Low Nutrient Environment by Changing Biogeochemical Functions

PubMed Central

Ikeda, Seishi; Sasaki, Kazuhiro; Okubo, Takashi; Yamashita, Akifumu; Terasawa, Kimihiro; Bao, Zhihua; Liu, Dongyan; Watanabe, Takeshi; Murase, Jun; Asakawa, Susumu; Eda, Shima; Mitsui, Hisayuki; Sato, Tadashi; Minamisawa, Kiwamu

2014-01-01

Reduced fertilizer usage is one of the objectives of field management in the pursuit of sustainable agriculture. Here, we report on shifts of bacterial communities in paddy rice ecosystems with low (LN), standard (SN), and high (HN) levels of N fertilizer application (0, 30, and 300 kg N ha−1, respectively). The LN field had received no N fertilizer for 5 years prior to the experiment. The LN and HN plants showed a 50% decrease and a 60% increase in biomass compared with the SN plant biomass, respectively. Analyses of 16S rRNA genes suggested shifts of bacterial communities between the LN and SN root microbiomes, which were statistically confirmed by metagenome analyses. The relative abundances of Burkholderia, Bradyrhizobium and Methylosinus were significantly increased in root microbiome of the LN field relative to the SN field. Conversely, the abundance of methanogenic archaea was reduced in the LN field relative to the SN field. The functional genes for methane oxidation (pmo and mmo) and plant association (acdS and iaaMH) were significantly abundant in the LN root microbiome. Quantitative PCR of pmoA/mcrA genes and a 13C methane experiment provided evidence of more active methane oxidation in the rice roots of the LN field. In addition, functional genes for the metabolism of N, S, Fe, and aromatic compounds were more abundant in the LN root microbiome. These results suggest that low-N-fertilizer management is an important factor in shaping the microbial community structure containing key microbes for plant associations and biogeochemical processes in paddy rice ecosystems. PMID:24463575

Integrated Metagenomic and Physiochemical Analyses to Evaluate the Potential Role of Microbes in the Sand Filter of a Drinking Water Treatment System

PubMed Central

Bai, Yaohui; Liu, Ruiping; Liang, Jinsong; Qu, Jiuhui

2013-01-01

While sand filters are widely used to treat drinking water, the role of sand filter associated microorganisms in water purification has not been extensively studied. In the current investigation, we integrated molecular (based on metagenomic) and physicochemical analyses to elucidate microbial community composition and function in a common sand filter used to treat groundwater for potable consumption. The results revealed that the biofilm developed rapidly within 2 days (reaching ∼1011 prokaryotes per gram) in the sand filter along with abiotic and biotic particulates accumulated in the interstitial spaces. Bacteria (up to 90%) dominated the biofilm microbial community, with Alphaproteobacteria being the most common class. Thaumarchaeota was the sole phylum of Archaea, which might be involved in ammonia oxidation. Function annotation of metagenomic datasets revealed a number of aromatic degradation pathway genes, such as aromatic oxygenase and dehydrogenase genes, in the biofilm, suggesting a significant role for microbes in the breakdown of aromatic compounds in groundwater. Simultaneous nitrification and denitrification pathways were confirmed as the primary routes of nitrogen removal. Dissolved heavy metals in groundwater, e.g. Mn2+ and As3+, might be biologically oxidized to insoluble or easily adsorbed compounds and deposited in the sand filter. Our study demonstrated that the role of the microbial community in the sand filter treatment system are critical to effective water purification in drinking water. PMID:23593378

Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and novel therapeutic target in acute myeloid leukemia

PubMed Central

Porter, Christopher C.; Kim, Jihye; Fosmire, Susan; Gearheart, Christy M.; van Linden, Annemie; Baturin, Dmitry; Zaberezhnyy, Vadym; Patel, Purvi R.; Gao, Dexiang; Tan, Aik Choon; DeGregori, James

2011-01-01

Acute myeloid leukemia (AML) remains a therapeutic challenge despite increasing knowledge about the molecular origins of the disease, as the mechanisms of AML cell escape from chemotherapy remain poorly defined. We hypothesized that AML cells are addicted to molecular pathways in the context of chemotherapy and used complementary approaches to identify these addictions. Using novel molecular and computational approaches, we performed genome-wide shRNA screens to identify proteins that mediate AML cell fate after cytarabine exposure, gene expression profiling of AML cells exposed to cytarabine to identify genes with induced expression in this context, and examination of existing gene expression data from primary patient samples. The integration of these independent analyses strongly implicates cell cycle checkpoint proteins, particularly WEE1, as critical mediators of AML cell survival after cytarabine exposure. Knockdown of WEE1 in a secondary screen confirmed its role in AML cell survival. Pharmacologic inhibition of WEE1 in AML cell lines and primary cells is synergistic with cytarabine. Further experiments demonstrate that inhibition of WEE1 prevents S-phase arrest induced by cytarabine, broadening the functions of WEE1 that may be exploited therapeutically. These data highlight the power of integrating functional and descriptive genomics, and identify WEE1 as potential therapeutic target in AML. PMID:22289989

Assessment of conformational, spectral, antimicrobial activity, chemical reactivity and NLO application of Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone).

PubMed

Rawat, Poonam; Singh, R N

2015-04-05

An orange colored pyrrole dihydrazone: Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone) (PDBO) has been synthesized by reaction of oxalic acid dihydrazide with 2,5 diformyl-1H-pyrrole and has been characterized by spectroscopic analysis (1H, 13C NMR, UV-visible, FT-IR and DART Mass). The properties of the compound has been evaluated using B3LYP functional and 6-31G(d,p)/6-311+G(d,p) basis set. The symmetric (3319, 3320 cm(-1)) and asymmetric (3389, 3382 cm(-1)) stretching wave number confirm free NH2 groups in PDBO. NBO analysis shows, inter/intra molecular interactions within the molecule. Topological parameters have been analyzed by QTAIM theory and provide the existence of intramolecular hydrogen bonding (N-H⋯O). The local reactivity descriptors analyses determine the reactive sites within molecule. The calculated first hyperpolarizability value (β0=23.83×10(-30) esu) of pyrrole dihydrazone shows its suitability for non-linear optical (NLO) response. The preliminary bioassay suggested that the PDBO exhibits relatively good antibacterial and fungicidal activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, Aspergillus niger. The local reactivity descriptors--Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) analyses have been used to determine the reactive sites within molecule. Copyright © 2014 Elsevier B.V. All rights reserved.

IRF4 rs12203592 functional variant and melanoma survival.

PubMed

Potrony, Miriam; Rebollo-Morell, Aida; Giménez-Xavier, Pol; Zimmer, Lisa; Puig-Butille, Joan Anton; Tell-Marti, Gemma; Sucker, Antje; Badenas, Celia; Carrera, Cristina; Malvehy, Josep; Schadendorf, Dirk; Puig, Susana

2017-04-15

Inherited genetic factors may modulate clinical outcome in melanoma. Some low-to-medium risk genes in melanoma susceptibility play a role in melanoma outcome. Our aim was to assess the role of the functional IRF4 SNP rs12203592 in melanoma prognosis in two independent sets (Barcelona, N = 493 and Essen, N = 438). Genotype association analyses showed that the IRF4 rs12203592 T allele increased the risk of dying from melanoma in both sets (Barcelona: odds ratio [OR] = 6.53, 95% CI 1.38-30.87, Adj p = 0.032; Essen: OR = 1.68, 95% CI 1.04-2.72, Adj p = 0.035). Survival analyses only showed significance for the Barcelona set (hazard ratio = 4.58, 95% CI 1.11-18.92, Adj p = 0.036). This SNP was also associated with tumour localization, increasing the risk of developing melanoma in head or neck (OR = 1.79, 95% CI 1.07-2.98, Adj p = 0.032) and protecting from developing melanoma in the trunk (OR = 0.59, 95% CI 0.41-0.85, Adj p = 0.004). These findings suggest for the first time that IRF4 rs12203592 plays a role in the modulation of melanoma outcome and confirms its contribution to the localization of the primary tumour. © 2017 UICC.

Assessment of conformational, spectral, antimicrobial activity, chemical reactivity and NLO application of Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone)

NASA Astrophysics Data System (ADS)

Rawat, Poonam; Singh, R. N.

2015-04-01

An orange colored pyrrole dihydrazone: Pyrrole-2,5-dicarboxaldehyde bis(oxaloyldihydrazone) (PDBO) has been synthesized by reaction of oxalic acid dihydrazide with 2,5 diformyl-1H-pyrrole and has been characterized by spectroscopic analysis (1H, 13C NMR, UV-visible, FT-IR and DART Mass). The properties of the compound has been evaluated using B3LYP functional and 6-31G(d,p)/6-311+G(d,p) basis set. The symmetric (3319, 3320 cm-1) and asymmetric (3389, 3382 cm-1) stretching wave number confirm free NH2 groups in PDBO. NBO analysis shows, inter/intra molecular interactions within the molecule. Topological parameters have been analyzed by QTAIM theory and provide the existence of intramolecular hydrogen bonding (N-H⋯O). The local reactivity descriptors analyses determine the reactive sites within molecule. The calculated first hyperpolarizability value (β0 = 23.83 × 10-30 esu) of pyrrole dihydrazone shows its suitability for non-linear optical (NLO) response. The preliminary bioassay suggested that the PDBO exhibits relatively good antibacterial and fungicidal activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pyogenes, Candida albicans, Aspergillus niger. The local reactivity descriptors - Fukui functions (fk+, fk-), local softnesses (sk+, sk-) and electrophilicity indices (ωk+, ωk-) analyses have been used to determine the reactive sites within molecule.

Integrated metagenomic and physiochemical analyses to evaluate the potential role of microbes in the sand filter of a drinking water treatment system.

PubMed

Bai, Yaohui; Liu, Ruiping; Liang, Jinsong; Qu, Jiuhui

2013-01-01

While sand filters are widely used to treat drinking water, the role of sand filter associated microorganisms in water purification has not been extensively studied. In the current investigation, we integrated molecular (based on metagenomic) and physicochemical analyses to elucidate microbial community composition and function in a common sand filter used to treat groundwater for potable consumption. The results revealed that the biofilm developed rapidly within 2 days (reaching ≈ 10(11) prokaryotes per gram) in the sand filter along with abiotic and biotic particulates accumulated in the interstitial spaces. Bacteria (up to 90%) dominated the biofilm microbial community, with Alphaproteobacteria being the most common class. Thaumarchaeota was the sole phylum of Archaea, which might be involved in ammonia oxidation. Function annotation of metagenomic datasets revealed a number of aromatic degradation pathway genes, such as aromatic oxygenase and dehydrogenase genes, in the biofilm, suggesting a significant role for microbes in the breakdown of aromatic compounds in groundwater. Simultaneous nitrification and denitrification pathways were confirmed as the primary routes of nitrogen removal. Dissolved heavy metals in groundwater, e.g. Mn(2+) and As(3+), might be biologically oxidized to insoluble or easily adsorbed compounds and deposited in the sand filter. Our study demonstrated that the role of the microbial community in the sand filter treatment system are critical to effective water purification in drinking water.

Identification of a novel PSEN1 mutation (Leu232Pro) in a Korean patient with early-onset Alzheimer's disease and a family history of dementia.

PubMed

Park, Jiyun; An, Seong Soo A; Giau, Vo Van; Shim, Kyuhwan; Youn, Young Chul; Bagyinszky, Eva; Kim, SangYun

2017-08-01

In the present study, a novel mutation in exon 7 of presenilin 1 (Leu232Pro) was discovered in a Korean patient with early-onset Alzheimer's disease, who represented memory decline at 37 years of age, followed by impairment in spatial activity and concentrations and personality changes. Imaging analyses with magnetic resonance scan showed diffuse atrophy in the frontoparietal regions. Targeted next generation sequencing and Sanger sequencing identified a heterozygous T to C transition at position 695 (c.695T>C) of in presenilin 1 gene (PSEN1), resulting in a novel missense mutation at codon 232 from leucine to proline (L232P). Several family members of the patient developed dementia, suggesting an autosomal dominant inheritance; however, we were unable to perform a segregation analysis to confirm this. Since the proline may play a role as a helix breaker, this mutation could significantly disturb the transmembrane helix domain-V of PSEN1 and perturb its protein functions. This hypothesis was supported by the results from the in silico analyses, predicted a major kink on this helix. Several leucine>proline substitutions in other PSEN1 transmembrane helices revealed aggressive AD phenotypes. Future functional studies would be needed to evaluate the pathogenicity of this mutation in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

Ferulic Acid Promotes Hypertrophic Growth of Fast Skeletal Muscle in Zebrafish Model.

PubMed

Wen, Ya; Ushio, Hideki

2017-09-26

As a widely distributed and natural existing antioxidant, ferulic acid and its functions have been extensively studied in recent decades. In the present study, hypertrophic growth of fast skeletal myofibers was observed in adult zebrafish after ferulic acid administration for 30 days, being reflected in increased body weight, body mass index (BMI), and muscle mass, along with an enlarged cross-sectional area of myofibers. qRT-PCR analyses demonstrated the up-regulation of relative mRNA expression levels of myogenic transcriptional factors (MyoD, myogenin and serum response factor (SRF)) and their target genes encoding sarcomeric unit proteins involved in muscular hypertrophy (skeletal alpha-actin, myosin heavy chain, tropomyosin, and troponin I). Western blot analyses detected a higher phosphorylated level of zTOR (zebrafish target of rapamycin), p70S6K, and 4E-BP1, which suggests an enhanced translation efficiency and protein synthesis capacity of fast skeletal muscle myofibers. These changes in transcription and translation finally converge and lead to higher protein contents in myofibers, as confirmed by elevated levels of myosin heavy chain (MyHC), and an increased muscle mass. To the best of our knowledge, these findings have been reported for the first time in vivo and suggest potential applications of ferulic acid as functional food additives and dietary supplements owing to its ability to promote muscle growth.

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 enhanced spin-polarized transport behaviors through cobalt benzene-porphyrin-benzene molecular junctions: the effect of functional groups

NASA Astrophysics Data System (ADS)

Cheng, Jue-Fei; Zhou, Liping; Wen, Zhongqian; Yan, Qiang; Han, Qin; Gao, Lei

2017-05-01

The modification effects of the groups amino (NH2) and nitro (NO2) on the spin polarized transport properties of the cobalt benzene-porphyrin-benzene (Co-BPB) molecule coupled to gold (Au) nanowire electrodes are investigated by the nonequilibrium Green’s function method combined with the density functional theory. The calculation results show that functional groups can lead to the significant spin-filter effect, enhanced low-bias negative differential resistance (NDR) behavior and novel reverse rectifying effect in Co-BPB molecular junction. The locations and types of functional groups have distinct influences on spin-polarized transport performances. The configuration with NH2 group substituting H atom in central porphyrin ring has larger spin-down current compared to that with NO2 substitution. And Co-BPB molecule junction with NH2 group substituting H atom in side benzene ring shows reverse rectifying effect. Detailed analyses confirm that NH2 and NO2 group substitution change the spin-polarized transferred charge, which makes the highest occupied molecular orbitals (HOMO) of spin-down channel of Co-BPB closer to the Fermi level. And the shift of HOMO strengthens the spin-polarized coupling between the molecular orbitals and the electrodes, leading to the enhanced spin-polarized behavior. Our findings might be useful in the design of multi-functional molecular devices in the future.

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults

PubMed Central

Flodin, Pär; Jonasson, Lars S.; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C. J.

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas. PMID:28848424

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults.

PubMed

Flodin, Pär; Jonasson, Lars S; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C J

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO 2 -peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO 2 -related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO 2 -peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

Investigation of synthesized new vanadium(III) complexes of ditolyldithiophosphate ligands by spectroscopic, cyclic voltammetric, DFT, antimicrobial and cytotoxic studies

NASA Astrophysics Data System (ADS)

Kumar, Sandeep; Syed, Atiya; Andotra, Savit; Kaur, Ramanpreet; Vikas; Pandey, Sushil K.

2018-02-01

Vanadium(III) complexes with sulfur donor dithiophosphate ligands corresponding to [{(ArO)2PS2}3V] and [{(ArO)2PS2}2VCl.L] (Ar = o-, m-, p-CH3C6H4 and p-Cl-m-CH3C6H3; L = NC5H5, P(C6H5)3, have been synthesized and characterized by various physico-chemical techniques like elemental analyses, magnetic studies, ESI-Mass, IR, UV and heteronuclear NMR (1H, 13C and 31P) spectral studies. These analyses have contributed to the prediction of structure: by exhibiting significant v(P-S) and v(Pdbnd S) band shifting in comparative IR spectra; shifting of resonance signal in comparative 31P NMR spectra of ligands and complexes and stability of V(III) ion in the complexed state is confirmed by magnetic and UV studies. Therefore, the six coordinated geometry stabilizing the trivalent vanadium atom in the complexes and adducts, respectively has been confirmed. The cyclic voltammetric analyses presented the redox aptitude of the complex under analysis which can be utilized as catalyst in organic synthesis. The geometry of ligands and complexes has been optimized using density functional theory (DFT). The structural parameters, vibrational bands and energy gaps of frontier orbitals (HOMO-LUMO) have also been calculated. The calculated geometric and spectral results reproduced the experimental data with well agreement. The DFT computed frontier molecular orbitals (HOMO-LUMO) and their energies suggest charge transfer occurs within the complexes. Antimicrobial screening of the complexes against two bacterial strains: Gram-positive, Enterrococcus faecalis and Gram-negative, Eischerichia coli and fungus Fusarium oxysporum have shown potential bioactivity. A preliminary cytotoxic analysis has been carried out using the cultivated human cell lines: lung adeno carcinoma cell line A-549, leukemia cell line THP-1, prostate cancer cell line PC3 and colorectal cancer cell line HCT-116.

An evaluation of satellite-derived humidity and its relationship to convective development

NASA Technical Reports Server (NTRS)

Fuelberg, Henry E.

1993-01-01

An aircraft prototype of the High-Resolution Interferometer Sounder (HIS) was flown over Tennessee and northern Alabama during summer 1986. The HIS temperature and dewpoint soundings were examined on two flight days to determine their error characteristics and utility in mesoscale analyses. Random errors were calculated from structure functions while total errors were obtained by pairing the HIS soundings with radiosonde-derived profiles. Random temperature errors were found to be less than 1 C at most levels, but random dewpoint errors ranged from 1 to 5 C. Total errors of both parameters were considerably greater, with dewpoint errors especially large on the day having a pronounced subsidence inversion. Cumulus cloud cover on 15 June limited HIS mesoscale analyses on that day. Previously undetected clouds were found in many HIS fields of view, and these probably produced the low-level horizontal temperature and dewpoint variations observed in the retrievals. HIS dewpoints at 300 mb indicated a strong moisture gradient that was confirmed by GOES 6.7-micron imagery. HIS mesoscale analyses on 19 June revealed a tongue of humid air stretching across the study area. The moist region was confirmed by radiosonde data and imagery from the Multispectral Atmospheric Mapping Sensor (MAMS). Convective temperatures derived from HIS retrievals helped explain the cloud formation that occurred after the HIS overflights. Crude estimates of Bowen ratio were obtained from HIS data using a mixing-line approach. Values indicated that areas of large sensible heat flux were the areas of first cloud development. These locations were also suggested by GOES visible and infrared imagery. The HIS retrievals indicated that areas of thunderstorm formation were regions of greatest instability. Local landscape variability and atmospheric temperature and humidity fluctuations were found to be important factors in producing the cumulus clouds on 19 June. HIS soundings were capable of detecting some of this variability. The authors were impressed by HIS's performance on the two study days.

Phylogenomics and Divergence Dating of Fungus-Farming Ants (Hymenoptera: Formicidae) of the Genera Sericomyrmex and Apterostigma.

PubMed

Ješovnik, Ana; González, Vanessa L; Schultz, Ted R

2016-01-01

Fungus-farming ("attine") ants are model systems for studies of symbiosis, coevolution, and advanced eusociality. A New World clade of nearly 300 species in 15 genera, all attine ants cultivate fungal symbionts for food. In order to better understand the evolution of ant agriculture, we sequenced, assembled, and analyzed transcriptomes of four different attine ant species in two genera: three species in the higher-attine genus Sericomyrmex and a single lower-attine ant species, Apterostigma megacephala, representing the first genomic data for either genus. These data were combined with published genomes of nine other ant species and the honey bee Apis mellifera for phylogenomic and divergence-dating analyses. The resulting phylogeny confirms relationships inferred in previous studies of fungus-farming ants. Divergence-dating analyses recovered slightly older dates than most prior analyses, estimating that attine ants originated 53.6-66.7 million of years ago, and recovered a very long branch subtending a very recent, rapid radiation of the genus Sericomyrmex. This result is further confirmed by a separate analysis of the three Sericomyrmex species, which reveals that 92.71% of orthologs have 99% - 100% pairwise-identical nucleotide sequences. We searched the transcriptomes for genes of interest, most importantly argininosuccinate synthase and argininosuccinate lyase, which are functional in other ants but which are known to have been lost in seven previously studied attine ant species. Loss of the ability to produce the amino acid arginine has been hypothesized to contribute to the obligate dependence of attine ants upon their cultivated fungi, but the point in fungus-farming ant evolution at which these losses occurred has remained unknown. We did not find these genes in any of the sequenced transcriptomes. Although expected for Sericomyrmex species, the absence of arginine anabolic genes in the lower-attine ant Apterostigma megacephala strongly suggests that the loss coincided with the origin of attine ants.

Zinc Levels in Left Ventricular Hypertrophy.

PubMed

Huang, Lei; Teng, Tianming; Bian, Bo; Yao, Wei; Yu, Xuefang; Wang, Zhuoqun; Xu, Zhelong; Sun, Yuemin

2017-03-01

Zinc is one of the most important trace elements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and left ventricular hypertrophy (LVH). A total of 519 patients was enrolled and their serum zinc levels were measured in this study. We performed analyses on the relationship between zinc levels and LVH and the four LV geometry pattern patients: normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH. We performed further linear and multiple regression analyses to confirm the relationship between zinc and left ventricular mass (LVM), left ventricular mass index (LVMI), and relative wall thickness (RWT). Our data showed that zinc levels were 710.2 ± 243.0 μg/L in the control group and were 641.9 ± 215.2 μg/L in LVH patients. We observed that zinc levels were 715 ± 243.5 μg/L, 694.2 ± 242.7 μg/L, 643.7 ± 225.0 μg/L, and 638.7 ± 197.0 μg/L in normal LV geometry, concentric remodeling, eccentric LVH, and concentric LVH patients, respectively. We further found that there was a significant inverse linear relationship between zinc and LVM (p = 0.001) and LVMI (p = 0.000) but did not show a significant relationship with RWT (p = 0.561). Multiple regression analyses confirmed that the linear relationship between zinc and LVM and LVMI remained inversely significant. The present study revealed that serum zinc levels were significantly decreased in the LVH patients, especially in the eccentric LVH and concentric LVH patients. Furthermore, zinc levels were significantly inversely correlated with LVM and LVMI.

Structural pierce into molecular mechanism underlying Clostridium perfringens Epsilon toxin function.

PubMed

Khalili, Saeed; Jahangiri, Abolfazl; Hashemi, Zahra Sadat; Khalesi, Bahman; Mard-Soltani, Maysam; Amani, Jafar

2017-03-01

Epsilon toxin of the Clostridium perfringens garnered a lot of attention due to its potential for toxicity in humans, extreme potency for cytotoxicity in mice and lack of any approved therapeutics prescribed for human. However, the intricacies of the Epsilon toxin action mechanism are yet to be understood. In this regard, various in silico tools have been exploited to model and refine the 3D structure of the toxin and its two receptors. The receptor proteins were embedded into designed lipid membranes within an aqueous and ionized environment. Thereafter, the modeled structures subjected to series of consecutive molecular dynamics runs to achieve the most natural like coordination for each model. Ultimately, protein-protein interaction analyses were performed to understand the probable action mechanism. The obtained results successfully confirmed the accuracy of employed methods to achieve high quality models for the toxin and its receptors within their lipid bilayers. Molecular dynamics analyses lead the structures to a more native like coordination. Moreover, the results of previous empirical studies were confirmed, while new insights for action mechanisms including the detailed roles of Hepatitis A virus cellular receptor 1 (HAVCR1) and Myelin and lymphocyte protein (MAL) proteins were achieved. In light of previous and our observations, we suggested novel models which elucidated the existing interplay between potential players of Epsilon toxin action mechanism with detailed structural evidences. These models would pave the way to have more robust understanding of the Epsilon toxin biology, more precise vaccine construction and more successful drug (inhibitor) design. Copyright © 2017 Elsevier Ltd. All rights reserved.

Variability in platelet dense granule adenosine triphosphate release findings amongst patients tested multiple times as part of an assessment for a bleeding disorder.

PubMed

Badin, M S; Graf, L; Iyer, J K; Moffat, K A; Seecharan, J L; Hayward, C P M

2016-12-01

Lumi-aggregometry quantification of platelet dense granule adenosine triphosphate (ATP) release is commonly used for diagnosing platelet function disorders. As the test findings show considerable variability for healthy controls, we postulated that patient findings might also be variable and investigated patients who were assessed for dense granule ATP release defects more than once. Analyses were performed on prospectively collected data for first and second tests for subjects tested for dense granule ATP release defects more than once by the Hamilton Regional Laboratory Program (HRLMP) between January 2007 and June 2013 (cohort I). Similar analyses were performed for subjects who were recruited to a platelet disorder study (cohort II) and were assessed for ATP release defects more than once before October 2015. A total of 150 unique subjects had multiple ATP release tests. Results with individual agonists were variable for many subjects. While normal findings with all tested agonists were often confirmed by the second test (cohort I: 83%; cohort II: 100%), impaired release with multiple agonists was confirmed in only some subjects (cohort I: 34%; cohort II: 54%). Inconsistent findings were common (cohort I: 36%; cohort II: 39%). ISTH bleeding scores showed no relationship to the test findings. The finding of impaired ATP release with 2 or more agonists on both tests was not associated with an increased likelihood of a definite bleeding disorder. The variability in platelet dense granule ATP release findings amongst patients assessed for diagnostic purposes suggests that the test has limited value for diagnosing platelet disorders. © 2016 John Wiley & Sons Ltd.

A 2011 Updated Systematic Review and Clinical Practice Guideline for the Management of Malignant Extradural Spinal Cord Compression

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

Loblaw, D. Andrew, E-mail: andrew.loblaw@sunnybrook.ca; Mitera, Gunita; Ford, Michael

2012-10-01

Purpose: To update the 2005 Cancer Care Ontario practice guidelines for the diagnosis and treatment of adult patients with a suspected or confirmed diagnosis of extradural malignant spinal cord compression (MESCC). Methods: A review and analysis of data published from January 2004 to May 2011. The systematic literature review included published randomized control trials (RCTs), systematic reviews, meta-analyses, and prospective/retrospective studies. Results: An RCT of radiation therapy (RT) with or without decompressive surgery showed improvements in pain, ambulatory ability, urinary continence, duration of continence, functional status, and overall survival. Two RCTs of RT (30 Gy in eight fractions vs. 16more » Gy in two fractions; 16 Gy in two fractions vs. 8 Gy in one fraction) in patients with a poor prognosis showed no difference in ambulation, duration of ambulation, bladder function, pain response, in-field failure, and overall survival. Retrospective multicenter studies reported that protracted RT schedules in nonsurgical patients with a good prognosis improved local control but had no effect on functional or survival outcomes. Conclusions: If not medically contraindicated, steroids are recommended for any patient with neurologic deficits suspected or confirmed to have MESCC. Surgery should be considered for patients with a good prognosis who are medically and surgically operable. RT should be given to nonsurgical patients. For those with a poor prognosis, a single fraction of 8 Gy should be given; for those with a good prognosis, 30 Gy in 10 fractions could be considered. Patients should be followed up clinically and/or radiographically to determine whether a local relapse develops. Salvage therapies should be introduced before significant neurologic deficits occur.« less

Expression of plasma membrane receptor genes during megakaryocyte development

PubMed Central

Sun, Sijie; Wang, Wenjing; Latchman, Yvette; Gao, Dayong; Aronow, Bruce

2013-01-01

Megakaryocyte (MK) development is critically informed by plasma membrane-localized receptors that integrate a multiplicity of environmental cues. Given that the current understanding about receptors and ligands involved in megakaryocytopoiesis is based on single targets, we performed a genome-wide search to identify a plasma membrane receptome for developing MKs. We identified 40 transmembrane receptor genes as being upregulated during MK development. Seven of the 40 receptor-associated genes were selected to validate the dataset. These genes included: interleukin-9 receptor (IL9R), transforming growth factor, β receptor II (TGFBR2), interleukin-4 receptor (IL4R), colony stimulating factor-2 receptor-beta (CSFR2B), adiponectin receptor (ADIPOR2), thrombin receptor (F2R), and interleukin-21 receptor (IL21R). RNA and protein analyses confirmed their expression in primary human MKs. Matched ligands to IL9R, TGFBR2, IL4R, CSFR2B, and ADIPOR2 affected megakaryocytopoiesis. IL9 was unique in its ability to increase the number of MKs formed. In contrast, MK colony formation was inhibited by adiponectin, TGF-β, IL4, and GM-CSF. The thrombin-F2R axis affected platelet function, but not MK development, while IL21 had no apparent detectable effects. ADP-induced platelet aggregation was suppressed by IL9, TGF-β, IL4, and adiponectin. Overall, six of seven of the plasma membrane receptors were confirmed to have functional roles in MK and platelet biology. Also, results show for the first time that adiponectin plays a regulatory role in MK development. Together these data support a strong likelihood that the 40 transmembrane genes identified as being upregulated during MK development will be an important resource to the research community for deciphering the complex repertoire of environmental cues regulating megakaryocytopoiesis and/or platelet function. PMID:23321270

A three-step programmed method for the identification of causative gene mutations of maturity onset diabetes of the young (MODY).

PubMed

Li, Qian; Cao, Xi; Qiu, Hai-Yan; Lu, Jing; Gao, Rui; Liu, Chao; Yuan, Ming-Xia; Yang, Guang-Ran; Yang, Jin-Kui

2016-08-22

To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified. Copyright © 2016 Elsevier B.V. All rights reserved.

Sparse feature selection methods identify unexpected global cellular response to strontium-containing materials

PubMed Central

Autefage, Hélène; Littmann, Elena; Hedegaard, Martin A. B.; Von Erlach, Thomas; O’Donnell, Matthew; Burden, Frank R.; Winkler, David A.; Stevens, Molly M.

2015-01-01

Despite the increasing sophistication of biomaterials design and functional characterization studies, little is known regarding cells’ global response to biomaterials. Here, we combined nontargeted holistic biological and physical science techniques to evaluate how simple strontium ion incorporation within the well-described biomaterial 45S5 bioactive glass (BG) influences the global response of human mesenchymal stem cells. Our objective analyses of whole gene-expression profiles, confirmed by standard molecular biology techniques, revealed that strontium-substituted BG up-regulated the isoprenoid pathway, suggesting an influence on both sterol metabolite synthesis and protein prenylation processes. This up-regulation was accompanied by increases in cellular and membrane cholesterol and lipid raft contents as determined by Raman spectroscopy mapping and total internal reflection fluorescence microscopy analyses and by an increase in cellular content of phosphorylated myosin II light chain. Our unexpected findings of this strong metabolic pathway regulation as a response to biomaterial composition highlight the benefits of discovery-driven nonreductionist approaches to gain a deeper understanding of global cell–material interactions and suggest alternative research routes for evaluating biomaterials to improve their design. PMID:25831522

Syntheses, structural characterization, and DPPH radical scavenging activity of cocrystals of caffeine with 1- and 2-naphthoxyacetic acids

NASA Astrophysics Data System (ADS)

Suresh Kumar, G. S.; Seethalakshmi, P. G.; Sumathi, D.; Bhuvanesh, N.; Kumaresan, S.

2013-03-01

Caffeine:1-naphthoxyacetic acid [(caf)(1-naa)] and caffeine:2-naphthoxyacetic acid [(caf)(2-naa)] cocrystals have been synthesized and single crystals were grown by slow evaporation technique. The structures of the grown crystals were elucidated using single crystal X-ray diffraction analysis. Both the cocrystals belong to the monoclinic crystallographic system with space group P21/c, Z = 4, and α = γ = 90°, whereas β = 111.4244(18)° for [(caf)(1-naa)] and β = 109.281(6)° for [(caf)(2-naa)]. The crystal packing is predominantly stabilized by hydrogen bonding and π-π stacking interactions. The presence of unionized -COOH functional group in both the cocrystals was identified by FTIR spectral analysis. Thermal behavior and stability of both the cocrystals were studied by TGA/DTA analyses. Solvent-free formation of these cocrystals was confirmed by powder X-ray diffraction analyses. The theoretical energy of cocrystals showed that the formers have higher energy than cocrystals 1 and 2. DPPH radical scavenging activity of cocrystals 1 and 2 is slightly greater than the formers.

Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia.

PubMed

Verhoeven, Virginie J M; Hysi, Pirro G; Wojciechowski, Robert; Fan, Qiao; Guggenheim, Jeremy A; Höhn, René; MacGregor, Stuart; Hewitt, Alex W; Nag, Abhishek; Cheng, Ching-Yu; Yonova-Doing, Ekaterina; Zhou, Xin; Ikram, M Kamran; Buitendijk, Gabriëlle H S; McMahon, George; Kemp, John P; Pourcain, Beate St; Simpson, Claire L; Mäkelä, Kari-Matti; Lehtimäki, Terho; Kähönen, Mika; Paterson, Andrew D; Hosseini, S Mohsen; Wong, Hoi Suen; Xu, Liang; Jonas, Jost B; Pärssinen, Olavi; Wedenoja, Juho; Yip, Shea Ping; Ho, Daniel W H; Pang, Chi Pui; Chen, Li Jia; Burdon, Kathryn P; Craig, Jamie E; Klein, Barbara E K; Klein, Ronald; Haller, Toomas; Metspalu, Andres; Khor, Chiea-Chuen; Tai, E-Shyong; Aung, Tin; Vithana, Eranga; Tay, Wan-Ting; Barathi, Veluchamy A; Chen, Peng; Li, Ruoying; Liao, Jiemin; Zheng, Yingfeng; Ong, Rick T; Döring, Angela; Evans, David M; Timpson, Nicholas J; Verkerk, Annemieke J M H; Meitinger, Thomas; Raitakari, Olli; Hawthorne, Felicia; Spector, Tim D; Karssen, Lennart C; Pirastu, Mario; Murgia, Federico; Ang, Wei; Mishra, Aniket; Montgomery, Grant W; Pennell, Craig E; Cumberland, Phillippa M; Cotlarciuc, Ioana; Mitchell, Paul; Wang, Jie Jin; Schache, Maria; Janmahasatian, Sarayut; Janmahasathian, Sarayut; Igo, Robert P; Lass, Jonathan H; Chew, Emily; Iyengar, Sudha K; Gorgels, Theo G M F; Rudan, Igor; Hayward, Caroline; Wright, Alan F; Polasek, Ozren; Vatavuk, Zoran; Wilson, James F; Fleck, Brian; Zeller, Tanja; Mirshahi, Alireza; Müller, Christian; Uitterlinden, André G; Rivadeneira, Fernando; Vingerling, Johannes R; Hofman, Albert; Oostra, Ben A; Amin, Najaf; Bergen, Arthur A B; Teo, Yik-Ying; Rahi, Jugnoo S; Vitart, Veronique; Williams, Cathy; Baird, Paul N; Wong, Tien-Yin; Oexle, Konrad; Pfeiffer, Norbert; Mackey, David A; Young, Terri L; van Duijn, Cornelia M; Saw, Seang-Mei; Bailey-Wilson, Joan E; Stambolian, Dwight; Klaver, Caroline C; Hammond, Christopher J

2013-03-01

Refractive error is the most common eye disorder worldwide and is a prominent cause of blindness. Myopia affects over 30% of Western populations and up to 80% of Asians. The CREAM consortium conducted genome-wide meta-analyses, including 37,382 individuals from 27 studies of European ancestry and 8,376 from 5 Asian cohorts. We identified 16 new loci for refractive error in individuals of European ancestry, of which 8 were shared with Asians. Combined analysis identified 8 additional associated loci. The new loci include candidate genes with functions in neurotransmission (GRIA4), ion transport (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2 and BMP2) and eye development (SIX6 and PRSS56). We also confirmed previously reported associations with GJD2 and RASGRF1. Risk score analysis using associated SNPs showed a tenfold increased risk of myopia for individuals carrying the highest genetic load. Our results, based on a large meta-analysis across independent multiancestry studies, considerably advance understanding of the mechanisms involved in refractive error and myopia.

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

Rasmussen, K.A.; Neumann, A.C.; Haddad, R.I.

The stable-isotope composition ({delta}{sup 13}C) of total organic carbon (TOC) was measured as a function of depth throughout a 217-cm-thick sequence of Holocene carbonate sediment within the Bight of Abaco lagoon, Little Bahama Bank. Biofacies and lithofacies analyses indicate progressive banktop submergence and paleoenvironmental response during Holocene sea-level rise. Stable-isotope values shift markedly from {minus}27.7{per thousand} within the 7900 B.P. paleosol at the base of the core to {minus}11.1{per thousand} at the present-day sediment-water interface. An abrupt excursion toward heavy-isotope values records the first establishment of Thalassia seagrass upon open-marine flooding. A multitracer approach, combining biofacies, lithofacies, and stable-isotope analysismore » of TOC confirms that the dramatic +17{per thousand} shift observed in {delta}{sup 13}C was a direct result of sea-level rise and associated environmental changes over the banktop; there is little evidence of spurious diagenetic overprint. Stable-isotope analyses of organic carbon may enhance the reconstruction of carbonate sequences by revealing a distinctive geochemical signature of banktop flooding, including the onset of growth of otherwise unpreservable Thalassia seagrass.« less

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.

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

Mobile Genome Express (MGE): A comprehensive automatic genetic analyses pipeline with a mobile device.

PubMed

Yoon, Jun-Hee; Kim, Thomas W; Mendez, Pedro; Jablons, David M; Kim, Il-Jin

2017-01-01

The development of next-generation sequencing (NGS) technology allows to sequence whole exomes or genome. However, data analysis is still the biggest bottleneck for its wide implementation. Most laboratories still depend on manual procedures for data handling and analyses, which translates into a delay and decreased efficiency in the delivery of NGS results to doctors and patients. Thus, there is high demand for developing an automatic and an easy-to-use NGS data analyses system. We developed comprehensive, automatic genetic analyses controller named Mobile Genome Express (MGE) that works in smartphones or other mobile devices. MGE can handle all the steps for genetic analyses, such as: sample information submission, sequencing run quality check from the sequencer, secured data transfer and results review. We sequenced an Actrometrix control DNA containing multiple proven human mutations using a targeted sequencing panel, and the whole analysis was managed by MGE, and its data reviewing program called ELECTRO. All steps were processed automatically except for the final sequencing review procedure with ELECTRO to confirm mutations. The data analysis process was completed within several hours. We confirmed the mutations that we have identified were consistent with our previous results obtained by using multi-step, manual pipelines.

Non-LTE spectral analyses of the lately discovered DB-gap white dwarfs from the SDSS

NASA Astrophysics Data System (ADS)

Hügelmeyer, S. D.; Dreizler, S.

2009-06-01

For a long time, no hydrogen-deficient white dwarfs have been known that have effective temperature between 30 kK and < 45 kK, i. e. exceeding those of DB white dwarfs and having lower ones than DO white dwarfs. Therefore, this temperature range was long known as the DB-gap. Only recently, the SDSS provided spectra of several candidate DB-gap stars. First analyses based on model spectra calculated under the assumption of local thermodynamic equilibrium (LTE) confirmed that these stars had 30 kK < Teff < 45 kK (Eisenstein et al. 2006). It has been shown for DO white dwarfs that the relaxation of LTE is necessary to account for non local effects in the atmosphere caused by the intense radiation field. Therefore, we calculated a non-LTE model grid and re-analysed the aforementioned set of SDSS spectra. Our results confirm the existence of DB-gap white dwarfs.

Localization and phosphorylation of Plasmodium falciparum nicotinamide/nicotinate mononucleotide adenylyltransferase (PfNMNAT) in intraerythrocytic stages.

PubMed

Nieto, Carlos A; Sánchez, Lina M; Sánchez, Diana M; Díaz, Gonzalo J; Ramírez, María H

2018-04-11

Nicotinamide adenine dinucleotide (NAD+) is an essential molecule in the energy metabolism of living beings, and it has various cellular functions. The main enzyme in the biosynthesis of this nucleotide is nicotinamide/nicotinate mononucleotide adenylyltransferase (NMNAT, EC 2.7.7.1/18) because it is the convergence point for all known biosynthetic pathways. NMNATs have divergences in both the number of isoforms detected and their distribution, depending on the organism. In the laboratory of basic research in biochemistry (LIBBIQ: acronym in Spanish) the NMNATs of protozoan parasites (Leishmania braziliensis, Plasmodium falciparum, Trypanosoma cruzi, and Giardia duodenalis) have been studied, analysing their catalytic properties through the use of proteins. Recombinants and their cellular distribution essentially. In 2014, O'Hara et al. determined the cytoplasmic localization of NMNAT of P. falciparum, using a transgene coupled to GFP, however, the addition of labels to the study protein can modify several of its characteristics, including its sub-cellular localization. This study confirms the cytoplasmic localization of this protein in the parasite through recognition of the endogenous protein in the different stages of the asexual life cycle. Additionally, the study found that PfNMNAT could be a phosphorylation target at serine, tyrosine and threonine residues, and it shows variations during the asexual life cycle. These experiments confirmed that the parasite is situated in the cytoplasm, fulfilling the required functions of NAD+ in this compartment, the PfNMNAT is regulated in post-transcription processes, and can be regulated by phosphorylation in its residues.

Sequencing the transcriptome of milk production: milk trumps mammary tissue.

PubMed

Lemay, Danielle G; Hovey, Russell C; Hartono, Stella R; Hinde, Katie; Smilowitz, Jennifer T; Ventimiglia, Frank; Schmidt, Kimberli A; Lee, Joyce W S; Islas-Trejo, Alma; Silva, Pedro Ivo; Korf, Ian; Medrano, Juan F; Barry, Peter A; German, J Bruce

2013-12-12

Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation.

Arsenic(V) removal from aqueous solutions using an anion exchanger derived from coconut coir pith and its recovery.

PubMed

Anirudhan, T S; Unnithan, Maya R

2007-01-01

The performance of a new anion exchanger (AE) prepared from coconut coir pith (CP), for the removal of arsenic(V) [As(V)] from aqueous solutions was evaluated in this study. The adsorbent (CP-AE) carrying dimethylaminohydroxypropyl weak base functional group was synthesized by the reaction of CP with epichlorohydrin and dimethylamine followed by treatment of hydrochloric acid. IR spectroscopy results confirm the presence of -NH(+)(CH(3))(2)Cl(-) group in the adsorbent. XRD studies confirm the decrease of crystallinity in CP-AE compared to CP, and it favours the protrusion of the functional group into the aqueous medium. Batch experiments were conducted to examine the efficiency of the adsorbent on As(V) removal. Maximum removal of 99.2% was obtained for an initial concentration of 1 mgl(-1) As(V) at pH 7.0 and an adsorbent dose of 2 gl(-1). The kinetics of sorption of As(V) onto CP-AE was described using the pseudo-second-order model. The equilibrium isotherms were determined for different temperatures and the results were analysed using the Langmuir equation. The temperature dependence indicates an exothermic process. Utility of the adsorbent was tested by removing As(V) from simulated groundwater. Regeneration studies were performed using 0.1N HCl. Batch adsorption-desorption studies illustrate that CP-AE could be used to remove As(V) from ground water and other industrial effluents.

Cognitive correlates of verbal memory and verbal fluency in schizophrenia, and differential effects of various clinical symptoms between male and female patients.

PubMed

Brébion, Gildas; Villalta-Gil, Victoria; Autonell, Jaume; Cervilla, Jorge; Dolz, Montserrat; Foix, Alexandrina; Haro, Josep Maria; Usall, Judith; Vilaplana, Miriam; Ochoa, Susana

2013-06-01

Impairment of higher cognitive functions in patients with schizophrenia might stem from perturbation of more basic functions, such as processing speed. Various clinical symptoms might affect cognitive efficiency as well. Notably, previous research has revealed the role of affective symptoms on memory performance in this population, and suggested sex-specific effects. We conducted a post-hoc analysis of an extensive neuropsychological study of 88 patients with schizophrenia. Regression analyses were conducted on verbal memory and verbal fluency data to investigate the contribution of semantic organisation and processing speed to performance. The role of negative and affective symptoms and of attention disorders in verbal memory and verbal fluency was investigated separately in male and female patients. Semantic clustering contributed to verbal recall, and a measure of reading speed contributed to verbal recall as well as to phonological and semantic fluency. Negative symptoms affected verbal recall and verbal fluency in the male patients, whereas attention disorders affected these abilities in the female patients. Furthermore, depression affected verbal recall in women, whereas anxiety affected it in men. These results confirm the association of processing speed with cognitive efficiency in patients with schizophrenia. They also confirm the previously observed sex-specific associations of depression and anxiety with memory performance in these patients, and suggest that negative symptoms and attention disorders likewise are related to cognitive efficiency differently in men and women. Copyright © 2013 Elsevier B.V. All rights reserved.

Functional and Evolutionary Characterization of a UDP-Xylose Synthase Gene from the Plant Pathogen Xylella fastidiosa, Involved in the Synthesis of Bacterial Lipopolysaccharide.

PubMed

Alencar, Valquíria Campos; Jabes, Daniela Leite; Menegidio, Fabiano Bezerra; Sassaki, Guilherme Lanzi; de Souza, Lucas Rodrigo; Puzer, Luciano; Meneghetti, Maria Cecília Zorél; Lima, Marcelo Andrade; Tersariol, Ivarne Luis Dos Santos; de Oliveira, Regina Costa; Nunes, Luiz R

2017-02-07

Xylella fastidiosa is a plant-infecting bacillus, responsible for many important crop diseases, such as Pierce's disease of vineyards, citrus variegated chlorosis, and coffee leaf scorch (CLS), among others. Recent genomic comparisons involving two CLS-related strains, belonging to X. fastidiosa subsp. pauca, revealed that one of them carries a frameshift mutation that inactivates a gene encoding an oxidoreductase of the short-chain dehydrogenase/reductase (SDR) superfamily, which may play important roles in determining structural variations in bacterial glycans and glycoconjugates. However, the exact nature of this SDR has been a matter of controversy, as different annotations of X. fastidiosa genomes have implicated it in distinct reactions. To confirm the nature of this mutated SDR, a comparative analysis was initially performed, suggesting that it belongs to a subgroup of SDR decarboxylases, representing a UDP-xylose synthase (Uxs). Functional assays, using a recombinant derivative of this enzyme, confirmed its nature as XfUxs, and carbohydrate composition analyses, performed with lipopolysaccharide (LPS) molecules obtained from different strains, indicate that inactivation of the X. fastidiosa uxs gene affects the LPS structure among CLS-related X. fastidiosa strains. Finally, a comparative sequence analysis suggests that this mutation is likely to result in a morphological and evolutionary hallmark that differentiates two subgroups of CLS-related strains, which may influence interactions between these bacteria and their plant and/or insect hosts.

Epigenetic determinants of ovarian clear cell carcinoma biology

PubMed Central

Yamaguchi, Ken; Huang, Zhiqing; Matsumura, Noriomi; Mandai, Masaki; Okamoto, Takako; Baba, Tsukasa; Konishi, Ikuo; Berchuck, Andrew; Murphy, Susan K.

2015-01-01

Targeted approaches have revealed frequent epigenetic alterations in ovarian cancer, but the scope and relation of these changes to histologic subtype of disease is unclear. Genome-wide methylation and expression data for 14 clear cell carcinoma (CCC), 32 non-CCC, and 4 corresponding normal cell lines were generated to determine how methylation profiles differ between cells of different histological derivations of ovarian cancer. Consensus clustering showed that CCC is epigenetically distinct. Inverse relationships between expression and methylation in CCC were identified, suggesting functional regulation by methylation, and included 22 hypomethylated (UM) genes and 276 hypermethylated (HM) genes. Categorical and pathway analyses indicated that the CCC-specific UM genes were involved in response to stress and many contain hepatocyte nuclear factor (HNF) 1 binding sites, while the CCC-specific HM genes included members of the estrogen receptor alpha (ERalpha) network and genes involved in tumor development. We independently validated the methylation status of 17 of these pathway-specific genes, and confirmed increased expression of HNF1 network genes and repression of ERalpha pathway genes in CCC cell lines and primary cancer tissues relative to non-CCC specimens. Treatment of three CCC cell lines with the demethylating agent Decitabine significantly induced expression for all five genes analyzed. Coordinate changes in pathway expression were confirmed using two primary ovarian cancer datasets (p<0.0001 for both). Our results suggest that methylation regulates specific pathways and biological functions in CCC, with hypomethylation influencing the characteristic biology of the disease while hypermethylation contributes to the carcinogenic process. PMID:24382740

Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy.

PubMed

Gamage, I H; Jonker, A; Zhang, X; Yu, P

2014-01-24

The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm(-1) (carbonyl CO ester, mainly related to lipid structure conformation), ca. 1725-1482 cm(-1) (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm(-1) (mainly associated with structural carbohydrate) and ca. 1180-800 cm(-1) (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources and their corresponding co-products. Copyright © 2013 Elsevier B.V. All rights reserved.

Genetic and mechanistic evaluation for the weak A phenotype in Ael blood type with IVS6 + 5G>A ABO gene mutation.

PubMed

Chen, D-P; Sun, C-F; Ning, H-C; Peng, C-T; Wang, W-T; Tseng, C-P

2015-01-01

Ael is a rare blood type that is characterized by weak agglutination of RBCs when reacts with anti-A antibody in adsorption-elution test. Although IVS6 + 5G→A mutation is known to associate with the Ael blood type, genetic and mechanistic evaluation for the weak agglutination of Ael with IVS6 + 5G→A mutation has not yet been completely addressed. In this study, five cases of confirmed Ael individuals were analysed. The cDNAs for the A(el) alleles were obtained by cloning method for sequence analyses. The erythroleukemia K562 cells were used as the cell study model and were transfected with the A(el) expression construct. Flow cytometry analysis was then performed to determine the levels of surface antigen expression. The results indicated that IVS6 + 5G→A attributes to all cases of Ael . RT-PCR analyses revealed the presence of at least 10 types of aberrant A(el) splicing transcripts. Most of the transcripts caused early termination and produced non-functional protein during translation. Nevertheless, the transcript without exons 5-6 was predicted to generate functional Ael glycosyltransferase lacking 57 amino acids at the N-terminal segment. When the exons 5-6 deletion transcript was stably expressed in the K562 cells, weak agglutination of the cells can be induced by adding anti-A antibody followed by adsorption-elution test. This study demonstrates that aberrant splicing of A transcripts contributes to weak A expression and the weak agglutination of Ael -RBCs, adding to the complexity for the regulatory mechanisms of ABO gene expression. © 2014 International Society of Blood Transfusion.

Differential Retention of Gene Functions in a Secondary Metabolite Cluster.

PubMed

Reynolds, Hannah T; Slot, Jason C; Divon, Hege H; Lysøe, Erik; Proctor, Robert H; Brown, Daren W

2017-08-01

In fungi, distribution of secondary metabolite (SM) gene clusters is often associated with host- or environment-specific benefits provided by SMs. In the plant pathogen Alternaria brassicicola (Dothideomycetes), the DEP cluster confers an ability to synthesize the SM depudecin, a histone deacetylase inhibitor that contributes weakly to virulence. The DEP cluster includes genes encoding enzymes, a transporter, and a transcription regulator. We investigated the distribution and evolution of the DEP cluster in 585 fungal genomes and found a wide but sporadic distribution among Dothideomycetes, Sordariomycetes, and Eurotiomycetes. We confirmed DEP gene expression and depudecin production in one fungus, Fusarium langsethiae. Phylogenetic analyses suggested 6-10 horizontal gene transfers (HGTs) of the cluster, including a transfer that led to the presence of closely related cluster homologs in Alternaria and Fusarium. The analyses also indicated that HGTs were frequently followed by loss/pseudogenization of one or more DEP genes. Independent cluster inactivation was inferred in at least four fungal classes. Analyses of transitions among functional, pseudogenized, and absent states of DEP genes among Fusarium species suggest enzyme-encoding genes are lost at higher rates than the transporter (DEP3) and regulatory (DEP6) genes. The phenotype of an experimentally-induced DEP3 mutant of Fusarium did not support the hypothesis that selective retention of DEP3 and DEP6 protects fungi from exogenous depudecin. Together, the results suggest that HGT and gene loss have contributed significantly to DEP cluster distribution, and that some DEP genes provide a greater fitness benefit possibly due to a differential tendency to form network connections. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy

NASA Astrophysics Data System (ADS)

Gamage, I. H.; Jonker, A.; Zhang, X.; Yu, P.

2014-01-01

The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm-1 (carbonyl Cdbnd O ester, mainly related to lipid structure conformation), ca. 1725-1482 cm-1 (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm-1 (mainly associated with structural carbohydrate) and ca. 1180-800 cm-1 (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources and their corresponding co-products.

Overexpression of FurA in Anabaena sp. PCC 7120 reveals new targets for this regulator involved in photosynthesis, iron uptake and cellular morphology.

PubMed

González, Andrés; Bes, M Teresa; Barja, François; Peleato, M Luisa; Fillat, María F

2010-11-01

Previous genomic analyses of the filamentous nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 have identified three ferric uptake regulator (Fur) homologs with low sequence identities and probably different functions in the cell. FurA is a constitutive protein that shares the highest homology with Fur from heterotrophic bacteria and appears to be essential for in vitro growth. In this study, we have analysed the effects of FurA overexpression on the Anabaena sp. phenotype and investigated which of the observed alterations were directly operated by FurA. Overexpression of the regulator led to changes in cellular morphology, resulting in shorter filaments with rounded cells of different sizes. The furA-overexpressing strain showed a slower photoautotrophic growth and a marked decrease in the oxygen evolution rate. Overexpression of the regulator also decreased both catalase and superoxide dismutase activities, but did not lead to an increase in the levels of intracellular reactive oxygen species. By combining phenotypic studies, reverse transcription-PCR analyses and electrophoretic mobility shift assays, we identified three novel direct targets of FurA, including genes encoding a siderophore outer membrane transporter (schT), bacterial actins (mreBCD) and the PSII reaction center protein D1 (psbA). The affinity of FurA for these novel targets was markedly affected by the absence of divalent metal ions, confirming previous evidence of a critical role for the metal co-repressor in the function of the regulator in vivo. The results unravel new cellular processes modulated by FurA, supporting its role as a global transcriptional regulator in Anabaena sp. PCC 7120.

Expression of neuronal markers in the endometrium of women with and those without endometriosis.

PubMed

Newman, T A; Bailey, J L; Stocker, L J; Woo, Y L; Macklon, N S; Cheong, Y C

2013-09-01

How do the expression patterns of neuronal markers differ in the endometrium of women with and without endometriosis? The neuronal markers, PGP9.5, NGFp75 and VR1, are expressed in the endometrium at levels that do not differ between women with and without endometriosis. Aberrant neuronal growth within the uterus may contribute to abnormal fertility and uterine dysfunction. However, controversy still exists as to whether aberrant innervation in the endometrium is associated with gynaecological pathology such as endometriosis. This may reflect the use of subjective methods such as histology to assess the innervation of the endometrium. We, therefore, employed a quantitative method, western blotting, to study markers of endometrial innervation in the presence and absence of endometriosis. This study included 45 women undergoing laparoscopic examination for the diagnosis of endometriosis. Endometrial samples were analysed by western blot for the expression of neuronal and neurotrophic markers, PGP9.5, VR1 and NGFp75. Endometrial pipelle biopsies were obtained from patients with (n = 20, study group) and without (n = 25, control group) endometriosis. Tissue was analysed by immunohistochemistry and western blot analysis for the expression of pan-neuronal marker, PGP9.5, sensory nociceptive marker, TPVR1, and low-affinity neurotrophic growth factor receptor, NGFRp75. PGP9.5, NGFp75 and VR1 were expressed in the endometrium of women, independent of the presence of endometriosis. Furthermore, the expression level of PGP9.5, VR1 and NGFp75 did not alter between the two cohorts of women. Studies of this nature are subject to the heterogeneous nature of patient population and tissue samples despite attempts to standardize these parameters. Hence, further studies using similar methodology will be required to confirm our results. Our results highlight that sensory neuronal markers are present in women with and without endometriosis. Future work will assess what the targets of the endometrial nerves are and investigate their function, their impact on endometrial biology and, in particular, whether aberrant neuronal function, rather than the mere presence of neuronal function, could be the root cause of subfertility and/or pain affecting many endometriosis sufferers. Our results do not, however, confirm the previous paradigm of increased innervation in the endometrium of women with endometriosis, nor the use of nerve cell detection from pipelle biopsies to diagnose endometriosis.

Non-linear clustering in the cold plus hot dark matter model

NASA Astrophysics Data System (ADS)

Bonometto, Silvio A.; Borgani, Stefano; Ghigna, Sebastiano; Klypin, Anatoly; Primack, Joel R.

1995-03-01

The main aim of this work is to find out if hierarchical scaling, observed in galaxy clustering, can be dynamically explained by studying N-body simulations. Previous analyses of dark matter (DM) particle distributions indicated heavy distortions with respect to the hierarchical pattern. Here, we shall describe how such distortions are to be interpreted and why they can be fully reconciled with the observed galaxy clustering. This aim is achieved by using high-resolution (512^3 grid-points) particle-mesh (PM) N-body simulations to follow the development of non-linear clustering in a Omega=1 universe, dominated either by cold dark matter (CDM) or by a mixture of cold+hot dark matter (CHDM) with Omega_cold=0.6, and Omega_hot=0.3 and Omega_baryon=0.1 a simulation box of side 100 Mpc (h=0.5) is used. We analyse two CHDM realizations with biasing factor b=1.5 (COBE normalization), starting from different initial random numbers, and compare them with CDM simulations with b=1 (COBE-compatible) and b=1.5. We evaluate high-order correlation functions and the void probability function (VPF). Correlation functions are obtained from both counts in cells and counts of neighbours. The analysis is carried out for DM particles and for galaxies identified as massive haloes of the evolved density field. We confirm that clustering of DM particles systematically exhibits deviations from hierarchical scaling, although the deviation increases somewhat in redshift space. Deviations from the hierarchical scaling of DM particles are found to be related to the spectrum shape, in a way that indicates that such distortions arise from finite sampling effects. We identify galaxy positions in the simulations and show that, quite differently from the DM particle background, galaxies follow hierarchical scaling (S_q=xi_q/& xgr^q-1_2=consta nt) far more closely, with reduced skewness and kurtosis coefficients S_3~2.5 and S_4~7.5, in general agreement with observational results. Unlike DM, the scaling of galaxy clustering is must marginally affected by redshift distortions and is obtained for both CDM and CHDM models. Hierarchical scaling in simulations is confirmed by VPF analysis. Also in this case, we find substantial agreement with observational findings.

Functional and taxonomic plant diversity for riverbank protection works: bioengineering techniques close to natural banks and beyond hard engineering.

PubMed

Cavaillé, Paul; Ducasse, Léon; Breton, Vincent; Dommanget, Fanny; Tabacchi, Eric; Evette, André

2015-03-15

Erosion control is a major issue in the Prealps region since piedmont is subject to both intense flood hazards and anthropic pressure. Riverbank protections may have major impacts on local ecosystem functioning and ecological corridor continuity. This study aimed to estimate the effects of the types of riverbank protection technique (from pure riprap to pure bioengineering) on the taxonomic and ecological composition of plant communities in comparison with unmanaged riverbanks as the referential system. Thirty-eight embankments were sampled in the foothills of the French and Swiss Alps. Four distinct riverbank techniques were analyzed and natural young willow stands were chosen as the referential system. At each site, vegetation was sampled along three transects from the waterline to the top of the riverbank. Plant communities were characterized using biological group composition (growth forms and life history, life strategies and distribution in space and time) and functional diversity indices (MFAD, FDc and wFDc). We identified 177 distinct plant species on 38 sites. Higher species richness levels were observed on bioengineered banks (from an average of 12 species recorded on ripraps to 27 species recorded on bioengineered banks) strongly dominated by Salicaceae species, especially for fascine and cribwall banks. Functional analyses of plant communities highlighted significant differences among bank types (p-value: 0.001) for all selected biological groups. Competitive - ruderal strategy, rooting shoots, stems or leaves that lie down or break off, and unisexual - dioecious, as well as pioneer plants and low shrubs (<4 m tall) distinguished bioengineered bank types. Functional diversity indices confirmed these differences among bank types (MFAD: p-value: 0.002; FDc: p-value: 0.003; wFDc: p-value: 0.005). Riprap always showed the lowest levels on functional diversity indices, fascine and cribwall banks were at the medium level and finally mixed and natural banks the highest level. These results confirm the low ecological potential of purely hard engineering techniques and highlight the similarity of bioengineered techniques and unmanaged riverbanks. Copyright © 2014 Elsevier Ltd. All rights reserved.

SLO-1-Channels of Parasitic Nematodes Reconstitute Locomotor Behaviour and Emodepside Sensitivity in Caenorhabditis elegans slo-1 Loss of Function Mutants

PubMed Central

Schniederjans, Monika; Miltsch, Sandra M.; Krücken, Jürgen; Guest, Marcus; Holden-Dye, Lindy; Harder, Achim; von Samson-Himmelstjerna, Georg

2011-01-01

The calcium-gated potassium channel SLO-1 in Caenorhabditis elegans was recently identified as key component for action of emodepside, a new anthelmintic drug with broad spectrum activity. In this study we identified orthologues of slo-1 in Ancylostoma caninum, Cooperia oncophora, and Haemonchus contortus, all important parasitic nematodes in veterinary medicine. Furthermore, functional analyses of these slo-1 orthologues were performed using heterologous expression in C. elegans. We expressed A. caninum and C. oncophora slo-1 in the emodepside-resistant genetic background of the slo-1 loss-of-function mutant NM1968 slo-1(js379). Transformants expressing A. caninum slo-1 from C. elegans slo-1 promoter were highly susceptible (compared to the fully emodepside-resistant slo-1(js379)) and showed no significant difference in their emodepside susceptibility compared to wild-type C. elegans (p = 0.831). Therefore, the SLO-1 channels of A. caninum and C. elegans appear to be completely functionally interchangeable in terms of emodepside sensitivity. Furthermore, we tested the ability of the 5′ flanking regions of A. caninum and C. oncophora slo-1 to drive expression of SLO-1 in C. elegans and confirmed functionality of the putative promoters in this heterologous system. For all transgenic lines tested, expression of either native C. elegans slo-1 or the parasite-derived orthologue rescued emodepside sensitivity in slo-1(js379) and the locomotor phenotype of increased reversal frequency confirming the reconstitution of SLO-1 function in the locomotor circuits. A potent mammalian SLO-1 channel inhibitor, penitrem A, showed emodepside antagonising effects in A. caninum and C. elegans. The study combined the investigation of new anthelmintic targets from parasitic nematodes and experimental use of the respective target genes in C. elegans, therefore closing the gap between research approaches using model nematodes and those using target organisms. Considering the still scarcely advanced techniques for genetic engineering of parasitic nematodes, the presented method provides an excellent opportunity for examining the pharmacofunction of anthelmintic targets derived from parasitic nematodes. PMID:21490955

Soy lecithin interferes with mitochondrial function in frozen-thawed ram spermatozoa.

PubMed

Del Valle, I; Gómez-Durán, A; Holt, W V; Muiño-Blanco, T; Cebrián-Pérez, J A

2012-01-01

Egg yolk and milk are the 2 major membrane cryoprotectants commonly used in freezing media for the long-term preservation of semen (alone or in combination with others). However, in recent years, there have been increasing arguments against the use of egg yolk or milk because of the risk of introducing diseases through the use of cryopreserved semen. In this study, we analyzed the protective effect of lecithin as an alternative to egg yolk for the cryopreservation of ram semen, using a range of functional markers for sperm viability, motility, apoptosis, and mitochondrial functionality analyses (mitochondrial inner membrane surface [MIMS], mitochondrial inner membrane potential [MIMP], and cell membrane potential) as methods of assessment in samples diluted in 3 different media: Tris-citrate-glucose as control and 2 media supplemented with soy lecithin or egg yolk. The results showed that lecithin was able to effectively protect certain sperm quality characteristics against freezing-induced damage. However, lecithin induced loss of mitochondrial membrane potential or mitochondrial loss that was not reflected by modifications in sperm motility in fresh semen. MIMS and MIMP values decreased in thawed lecithin-treated samples, concomitant with a lower (P < .05) percentage of total and progressively motile cells, compared with those in egg yolk-containing samples. Further incubation of thawed samples revealed changes in motility and mitochondrial functionality that otherwise would not have been detected. These results indicated that lecithin may have affected the inner mitochondrial membrane in frozenthawed spermatozoa and confirmed that sublethal damages that seriously affect sperm functionality, not detected by classic sperm quality analyses, can be evidenced by changes in the inner mitochondrial membrane surface. These findings strengthen the relationship between mitochondrial membrane potential and motility and show that the mitochondrial alterations induced by the cryopreservation process could be specific targets for the improvement of semen cryopreservation protocols.

A neuropsychological assessment of frontal cognitive functions in Prader-Willi syndrome.

PubMed

Jauregi, J; Arias, C; Vegas, O; Alén, F; Martinez, S; Copet, P; Thuilleaux, D

2007-05-01

Prader-Willi syndrome (PWS) is associated with a characteristic behavioural phenotype whose main features are, alongside compulsive hyperphagia, deficits in social behaviour: social withdrawal, temper tantrums, perseverative speech and behaviour, mental rigidity, stereotyped behaviour, impulsiveness, etc. Similar symptoms may also be found in autistic spectrum disorders and lesional pathologies of the frontal lobe. In both cases, such symptoms have been related to dysfunctions in frontal cognitive processes such as attention, working memory and executive functions. This study uses standardized neuropsychological instruments to analyse the degree to which these processes are affected in PWS. The sample comprised 16 individuals with a genetically confirmed PWS diagnosis. Subjects' IQ (Wechsler Adult Intelligence Scale), academic level, laterality and body mass index (BMI) were calculated. Attention, memory and executive functions were analysed using standard, widely employed neuropsychological tests. We compared the results of the sample group with the general population. Correlation analyses were carried out with IQ, academic level and BMI. In all the neuropsychological measures focusing on attention, executive functions and visuoperceptual organization, the study sample scored significantly lower than the normative reference population. The scores of the tests used for measuring immediate memory were also significantly lower when trials required sequential processing, although not when they required simultaneous processing. In the memorization of a list of words, subjects showed an initial deficit which disappeared with repetition, enabling them to obtain scores similar to the reference population. No significant correlations were found with BMI, and a higher IQ or academic level did not improve scores in the majority of tests. The study shows a deficit in elementary frontal cognitive processes in PWS patients. This deficit may be involved in the social behaviour disorders that characterize such patients, as described in other development or frontal syndrome pathologies. However, we cannot affirm that the deficits found are specific to PWS; they could also occur in other causes of intellectual disability. Although in the study sample IQ did not correlate with frontal deficits, further research is needed to establish whether the neuropsychological alterations described form part of a cognitive phenotype for PWS. We believe that our understanding of the social behaviours typical of PWS may be improved by taking into consideration the cognitive functioning models of the prefrontal lobe, particularly those applied to pervasive developmental disorders.

Altered spinal microRNA-146a and the microRNA-183 cluster contribute to osteoarthritic pain in knee joints.

PubMed

Li, Xin; Kroin, Jeffrey S; Kc, Ranjan; Gibson, Gary; Chen, Di; Corbett, Grant T; Pahan, Kalipada; Fayyaz, Sana; Kim, Jae-Sung; van Wijnen, Andre J; Suh, Joon; Kim, Su-Gwan; Im, Hee-Jeong

2013-12-01

The objective of this study was to examine whether altered expression of microRNAs in central nervous system components is pathologically linked to chronic knee joint pain in osteoarthritis. A surgical animal model for knee joint OA was generated by medial meniscus transection in rats followed by behavioral pain tests. Relationships between pathological changes in knee joint and development of chronic joint pain were examined by histology and imaging analyses. Alterations in microRNAs associated with OA-evoked pain sensation were determined in bilateral lumbar dorsal root ganglia (DRG) and the spinal dorsal horn by microRNA array followed by individual microRNA analyses. Gain- and loss-of-function studies of selected microRNAs (miR-146a and miR-183 cluster) were conducted to identify target pain mediators regulated by these selective microRNAs in glial cells. The ipsilateral hind leg displayed significantly increased hyperalgesia after 4 weeks of surgery, and sensitivity was sustained for the remainder of the 8-week experimental period (F = 341, p < 0.001). The development of OA-induced chronic pain was correlated with pathological changes in the knee joints as assessed by histological and imaging analyses. MicroRNA analyses showed that miR-146a and the miR-183 cluster were markedly reduced in the sensory neurons in DRG (L4/L5) and spinal cord from animals experiencing knee joint OA pain. The downregulation of miR-146a and/or the miR-183 cluster in the central compartments (DRG and spinal cord) are closely associated with the upregulation of inflammatory pain mediators. The corroboration between decreases in these signature microRNAs and their specific target pain mediators were further confirmed by gain- and loss-of-function analyses in glia, the major cellular component of the central nervous system (CNS). MicroRNA therapy using miR-146a and the miR-183 cluster could be powerful therapeutic intervention for OA in alleviating joint pain and concomitantly regenerating peripheral knee joint cartilage. © 2013 American Society for Bone and Mineral Research.

Media's Moral Messages: Assessing Perceptions of Moral Content in Television Programming

ERIC Educational Resources Information Center

Glover, Rebecca J.; Garmon, Lance C.; Hull, Darrell M.

2011-01-01

This study extends the examination of moral content in the media by exploring moral messages in television programming and viewer characteristics predictive of the ability to perceive such messages. Generalisability analyses confirmed the reliability of the Media's Moral Messages (MMM) rating form for analysing programme content and the existence…

Hepatitis B virus genetic mutations and evolution in liver diseases

PubMed Central

Shen, Tao; Yan, Xin-Min

2014-01-01

Hepatitis B virus (HBV) belongs to the genus Orthohepadnavirus of the Hepadnaviridae family and is approximately 3.2 kb in length. Owing to a lack of proofreading capacity during reverse transcription and a high replication rate, HBV exhibits as quasispecies. To detect the genetic mutations of HBV, many methods with different sensitivities and throughputs were developed. According to documentary records, HBV mutation and evolution were important vial parameters in predicting disease progression and therapeutic outcome. In this review, we separately discussed the correlation between HBV genomic mutations in four open reading frames and liver disease progression. Since some of the results were controversial from different laboratories, it remains to be seen whether functional analyses will confirm their role in modifying the course of infection. PMID:24833874

Transmission and reassortment of avian influenza viruses at the Asian-North American interface

USGS Publications Warehouse

Ramey, Andrew M.; Pearce, John M.; Ely, Craig R.; Guy, Lisa M. Sheffield; Irons, David B.; Derksen, Dirk V.; Ip, Hon S.

2010-01-01

Twenty avian influenza viruses were isolated from seven wild migratory bird species sampled at St. Lawrence Island, Alaska. We tested predictions based on previous phylogenetic analyses of avian influenza viruses that support spatially dependent trans-hemispheric gene flow and frequent interspecies transmission at a location situated at the Asian–North American interface. Through the application of phylogenetic and genotypic approaches, our data support functional dilution by distance of trans-hemispheric reassortants and interspecific virus transmission. Our study confirms infection of divergent avian taxa with nearly identical avian influenza strains in the wild. Findings also suggest that H16N3 viruses may contain gene segments with unique phylogenetic positions and that further investigation of how host specificity may impact transmission of H13 and H16 viruses is warranted.

A cross-cultural comparison of the coexistence and domain superiority of individuating and relating autonomy.

PubMed

Yeh, Kuang-Hui; Bedford, Olwen; Yang, Yung-Jui

2009-06-01

The consensus definition of autonomy in the psychological literature emphasizes self-governance through free volition, not separation or independence from others. Since the concept of self may differ cross-culturally, several researchers have tried to incorporate types of self into the notion of autonomy; however, only the dual model of autonomy has been able to do this while retaining an emphasis on volition. The dual model describes two distinct forms of autonomy-individuating and relating-each with superior function in a specific domain of individual functioning. Individuating autonomy represents a volitional capacity to act against social constraints and offers a route to achieve an independent self-identity by expressing individualistic attributes and distinctions. Relating autonomy represents a volitional capacity to act by emphasizing the harmony of self-in-relation-to-others, the quality of interpersonal relationships, and self-transcendence. These two forms of autonomy have been shown to coexist at the individual level in a Taiwanese sample. This study takes the next step, with a cross-cultural test of the coexistence and domain superiority hypotheses of individuating and relating autonomy. Participants included 306 college students from Taiwan and 183 college students from the United States. Structural equation modelling by multigroup analyses confirmed the cross-cultural equivalence of the two-factor individuating autonomy and relating autonomy measurement model. Across both samples the two forms of autonomy were shown to be mutually inclusive and not exclusive or independent. The domain-superior function of each form of autonomy was also confirmed cross-culturally; each form of autonomy has a dominant, but not necessarily exclusive, domain of functioning. Specifically, individuating autonomy was more associated with intrapersonal than interpersonal domain dependent variables, while relating autonomy was more associated with interpersonal than intrapersonal domain dependent variables. Limitations of the study and considerations for future research are discussed.

Chemokine interactome mapping enables tailored intervention in acute and chronic inflammation.

PubMed

von Hundelshausen, Philipp; Agten, Stijn M; Eckardt, Veit; Blanchet, Xavier; Schmitt, Martin M; Ippel, Hans; Neideck, Carlos; Bidzhekov, Kiril; Leberzammer, Julian; Wichapong, Kanin; Faussner, Alexander; Drechsler, Maik; Grommes, Jochen; van Geffen, Johanna P; Li, He; Ortega-Gomez, Almudena; Megens, Remco T A; Naumann, Ronald; Dijkgraaf, Ingrid; Nicolaes, Gerry A F; Döring, Yvonne; Soehnlein, Oliver; Lutgens, Esther; Heemskerk, Johan W M; Koenen, Rory R; Mayo, Kevin H; Hackeng, Tilman M; Weber, Christian

2017-04-05

Chemokines orchestrate leukocyte trafficking and function in health and disease. Heterophilic interactions between chemokines in a given microenvironment may amplify, inhibit, or modulate their activity; however, a systematic evaluation of the chemokine interactome has not been performed. We used immunoligand blotting and surface plasmon resonance to obtain a comprehensive map of chemokine-chemokine interactions and to confirm their specificity. Structure-function analyses revealed that chemokine activity can be enhanced by CC-type heterodimers but inhibited by CXC-type heterodimers. Functional synergism was achieved through receptor heteromerization induced by CCL5-CCL17 or receptor retention at the cell surface via auxiliary proteoglycan binding of CCL5-CXCL4. In contrast, inhibitory activity relied on conformational changes (in CXCL12), affecting receptor signaling. Obligate CC-type heterodimers showed high efficacy and potency and drove acute lung injury and atherosclerosis, processes abrogated by specific CCL5-derived peptide inhibitors or knock-in of an interaction-deficient CXCL4 variant. Atheroprotective effects of CCL17 deficiency were phenocopied by a CCL5-derived peptide disrupting CCL5-CCL17 heterodimers, whereas a CCL5 α-helix peptide mimicked inhibitory effects on CXCL12-driven platelet aggregation. Thus, formation of specific chemokine heterodimers differentially dictates functional activity and can be exploited for therapeutic targeting. Copyright © 2017, American Association for the Advancement of Science.

Structure and function of the abductors in patients with hip osteoarthritis: Systematic review and meta-analysis.

PubMed

Marshall, Amelia Rose; Noronha, Marcos de; Zacharias, Anita; Kapakoulakis, Theo; Green, Rodney

2016-04-27

Hip osteoarthritis (OA) is a major cause of morbidity. Rehabilitation for this population focuses on strengthening the hip muscles, particularly the abductors, however the deficit in function of these muscles is unclear. To review the evidence for the differences in structure and function of hip abductors (gluteus medius and minimus and tensor fascia lata) in hip OA. A systematic review was conducted using MEDLINE, AMED, CINAHL and SportDISCUS, from the earliest date to September 2013. Studies that compared hip OA patients with controls, or the unaffected contralateral hip were included. Studies needed to report data on an outcome related to gross gluteal muscle function. An initial yield of 141 studies was reduced to 22 after application of inclusion/exclusion criteria. Meta-analysis confirmed greater hip abductor strength in the control group (standardized mean difference = SMD -0.93, 95%CI -1.70 to -0.16) and the unaffected limb (SMD -0.26, 95%CI -0.48 to -0.04). Meta-analyses showed no differences in muscle size either between groups or limbs. Few electromyography studies have been reported and meta-analysis was not possible. Hip abductor strength is reduced in OA patients when compared to healthy controls and to the unaffected limb. Data on muscle size and activity is limited.

Comparative expression profiling reveals gene functions in female meiosis and gametophyte development in Arabidopsis.

PubMed

Zhao, Lihua; He, Jiangman; Cai, Hanyang; Lin, Haiyan; Li, Yanqiang; Liu, Renyi; Yang, Zhenbiao; Qin, Yuan

2014-11-01

Megasporogenesis is essential for female fertility, and requires the accomplishment of meiosis and the formation of functional megaspores. The inaccessibility and low abundance of female meiocytes make it particularly difficult to elucidate the molecular basis underlying megasporogenesis. We used high-throughput tag-sequencing analysis to identify genes expressed in female meiocytes (FMs) by comparing gene expression profiles from wild-type ovules undergoing megasporogenesis with those from the spl mutant ovules, which lack megasporogenesis. A total of 862 genes were identified as FMs, with levels that are consistently reduced in spl ovules in two biological replicates. Fluorescence-assisted cell sorting followed by RNA-seq analysis of DMC1:GFP-labeled female meiocytes confirmed that 90% of the FMs are indeed detected in the female meiocyte protoplast profiling. We performed reverse genetic analysis of 120 candidate genes and identified four FM genes with a function in female meiosis progression in Arabidopsis. We further revealed that KLU, a putative cytochrome P450 monooxygenase, is involved in chromosome pairing during female meiosis, most likely by affecting the normal expression pattern of DMC1 in ovules during female meiosis. Our studies provide valuable information for functional genomic analyses of plant germline development as well as insights into meiosis. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Plasticity of genetic interactions in metabolic networks of yeast.

PubMed

Harrison, Richard; Papp, Balázs; Pál, Csaba; Oliver, Stephen G; Delneri, Daniela

2007-02-13

Why are most genes dispensable? The impact of gene deletions may depend on the environment (plasticity), the presence of compensatory mechanisms (mutational robustness), or both. Here, we analyze the interaction between these two forces by exploring the condition-dependence of synthetic genetic interactions that define redundant functions and alternative pathways. We performed systems-level flux balance analysis of the yeast (Saccharomyces cerevisiae) metabolic network to identify genetic interactions and then tested the model's predictions with in vivo gene-deletion studies. We found that the majority of synthetic genetic interactions are restricted to certain environmental conditions, partly because of the lack of compensation under some (but not all) nutrient conditions. Moreover, the phylogenetic cooccurrence of synthetically interacting pairs is not significantly different from random expectation. These findings suggest that these gene pairs have at least partially independent functions, and, hence, compensation is only a byproduct of their evolutionary history. Experimental analyses that used multiple gene deletion strains not only confirmed predictions of the model but also showed that investigation of false predictions may both improve functional annotation within the model and also lead to the discovery of higher-order genetic interactions. Our work supports the view that functional redundancy may be more apparent than real, and it offers a unified framework for the evolution of environmental adaptation and mutational robustness.

[Emerging novel therapeutic strategy for α-dystroglycanopathy by Large].

PubMed

Saito, Fumiaki

2011-11-01

The past decade of researches have revealed mutations of known or putative glycosyltransferases in several types of muscular dystrophy, including Fukuyama-type congenital muscular dystrophy. In these disorders, the function of α-dystroglycan is severely decreased, therefore they are called α-dystroglycanopathy. Recently, putative glycosyltransferase Large was shown to restore the defective function of α-dystroglycan, thus, it is an intriguing idea to apply this effect to the therapy of α-dystroglycanopathy. In the present study, we sought to test this possibility. Using several cultured cell lines, we confirmed that the overexpression of Large results in hyperglycosylation and marked enhancement of the function of α-dystroglycan. For this effect, the whole luminal domain of Large was shown to be necessary using several deletion constructs. We further generated transgenic mice overexpressing Large ubiquitously. In each tissue of the mice, the glycosylation of α-dystroglycan and its laminin binding activity was remarkably increased. Moreover, the morphological analyses on each tissue stained by H-E revealed no significant abnormality in the transgenic mice, suggesting no serious side effects by the overexpression of Large. Taken together, these results indicate that the restoration of the function of α-dystroglycan by Large should be an important molecular target to develop therapeutic strategies for α-dystroglycanopathy.

Plasma asymmetric dimethylarginine, L-arginine and left ventricular structure and function in a community-based sample.

PubMed

Lieb, Wolfgang; Benndorf, Ralf A; Benjamin, Emelia J; Sullivan, Lisa M; Maas, Renke; Xanthakis, Vanessa; Schwedhelm, Edzard; Aragam, Jayashri; Schulze, Friedrich; Böger, Rainer H; Vasan, Ramachandran S

2009-05-01

Increasing evidence indicates that cardiac structure and function are modulated by the nitric oxide (NO) system. Elevated plasma concentrations of asymmetric dimethylarginine (ADMA; a competitive inhibitor of NO synthase) have been reported in patients with end-stage renal disease. It is unclear if circulating ADMA and L-arginine levels are related to cardiac structure and function in the general population. We related plasma ADMA and L-arginine (the amino acid precursor of NO) to echocardiographic left ventricular (LV) mass, left atrial (LA) size and fractional shortening (FS) using multivariable linear regression analyses in 1919 Framingham Offspring Study participants (mean age 57 years, 58% women). Overall, neither ADMA or L-arginine, nor their ratio was associated with LV mass, LA size and FS in multivariable models (p>0.10 for all). However, we observed effect modification by obesity of the relations of ADMA and LA size (p for interaction p=0.04): ADMA was positively related to LA size in obese individuals (adjusted-p=0.0004 for trend across ADMA quartiles) but not in non-obese people. In our large community-based sample, plasma ADMA and l-arginine concentrations were not related to cardiac structure or function. The observation of positive relations of LA size and ADMA in obese individuals warrants confirmation.

Functional characterization of putative cilia genes by high-content analysis

PubMed Central

Lai, Cary K.; Gupta, Nidhi; Wen, Xiaohui; Rangell, Linda; Chih, Ben; Peterson, Andrew S.; Bazan, J. Fernando; Li, Li; Scales, Suzie J.

2011-01-01

Cilia are microtubule-based protrusions from the cell surface that are involved in a number of essential signaling pathways, yet little is known about many of the proteins that regulate their structure and function. A number of putative cilia genes have been identified by proteomics and comparative sequence analyses, but functional data are lacking for the vast majority. We therefore monitored the effects in three cell lines of small interfering RNA (siRNA) knockdown of 40 of these genes by high-content analysis. We assayed cilia number, length, and transport of two different cargoes (membranous serotonin receptor 6-green fluorescent protein [HTR6-GFP] and the endogenous Hedgehog [Hh] pathway transcription factor Gli3) by immunofluorescence microscopy; and cilia function using a Gli-luciferase Hh signaling assay. Hh signaling was most sensitive to perturbations, with or without visible structural cilia defects. Validated hits include Ssa2 and mC21orf2 with ciliation defects; Ift46 with short cilia; Ptpdc1 and Iqub with elongated cilia; and Arl3, Nme7, and Ssna1 with distinct ciliary transport but not length defects. Our data confirm various ciliary roles for several ciliome proteins and show it is possible to uncouple ciliary cargo transport from cilia formation in vertebrates. PMID:21289087

The regulatory network analysis of long noncoding RNAs in human colorectal cancer.

PubMed

Zhang, Yuwei; Tao, Yang; Li, Yang; Zhao, Jinshun; Zhang, Lina; Zhang, Xiaohong; Dong, Changzheng; Xie, Yangyang; Dai, Xiaoyu; Zhang, Xinjun; Liao, Qi

2018-05-01

Colorectal cancer (CRC) is among one of the most prevalent and lethiferous diseases worldwide. Long noncoding RNAs (lncRNAs) are commonly accepted to function as a key regulatory factor in human cancer, but the potential regulatory mechanisms of CRC-associated lncRNA are largely obscure. Here, we integrated several expression profiles to obtain 55 differentially expressed (DE) lncRNAs. We first detected lncRNA interactions with transcription factors, microRNAs, mRNAs, and RNA-binding proteins to construct a regulatory network and then create functional enrichment analyses for them using bioinformatics approaches. We found the upregulated genes in the regulatory network are enriched in cell cycle and DNA damage response, while the downregulated genes are enriched in cell differentiation, cellular response, and cell signaling. We then employed module-based methods to mine several intriguing modules from the overall network, which helps to classify the functions of genes more specifically. Next, we confirmed the validity of our network by comparisons with a randomized network using computational method. Finally, we attempted to annotate lncRNA functions based on the regulatory network, which indicated its potential application. Our study of the lncRNA regulatory network provided significant clues to unveil lncRNAs potential regulatory mechanisms in CRC and laid a foundation for further experimental investigation.

Personality and Neural Correlates of Mentalizing Ability.

PubMed

Allen, Timothy A; Rueter, Amanda R; Abram, Samantha V; Brown, James S; DeYoung, Colin G

2017-01-01

Theory of mind, or mentalizing , defined as the ability to reason about another's mental states, is a crucial psychological function that is disrupted in some forms of psychopathology, but little is known about how individual differences in this ability relate to personality or brain function. One previous study linked mentalizing ability to individual differences in the personality trait Agreeableness. Agreeableness encompasses two major subdimensions: Compassion reflects tendencies toward empathy, prosocial behavior, and interpersonal concern, whereas Politeness captures tendencies to suppress aggressive and exploitative impulses. We hypothesized that Compassion but not Politeness would be associated with better mentalizing ability. This hypothesis was confirmed in Study 1 ( N = 329) using a theory of mind task that required reasoning about the beliefs of fictional characters. Post hoc analyses indicated that the honesty facet of Agreeableness was negatively associated with mentalizing. In Study 2 ( N = 217), we examined whether individual differences in mentalizing and related traits were associated with patterns of resting-state functional connectivity in the brain. Performance on the theory of mind task was significantly associated with patterns of connectivity between the dorsal medial and core subsystems of the default network, consistent with evidence implicating these regions in mentalization.

Metabolomics and Cheminformatics Analysis of Antifungal Function of Plant Metabolites

PubMed Central

Cuperlovic-Culf, Miroslava; Rajagopalan, NandhaKishore; Tulpan, Dan; Loewen, Michele C.

2016-01-01

Fusarium head blight (FHB), primarily caused by Fusarium graminearum, is a devastating disease of wheat. Partial resistance to FHB of several wheat cultivars includes specific metabolic responses to inoculation. Previously published studies have determined major metabolic changes induced by pathogens in resistant and susceptible plants. Functionality of the majority of these metabolites in resistance remains unknown. In this work we have made a compilation of all metabolites determined as selectively accumulated following FHB inoculation in resistant plants. Characteristics, as well as possible functions and targets of these metabolites, are investigated using cheminformatics approaches with focus on the likelihood of these metabolites acting as drug-like molecules against fungal pathogens. Results of computational analyses of binding properties of several representative metabolites to homology models of fungal proteins are presented. Theoretical analysis highlights the possibility for strong inhibitory activity of several metabolites against some major proteins in Fusarium graminearum, such as carbonic anhydrases and cytochrome P450s. Activity of several of these compounds has been experimentally confirmed in fungal growth inhibition assays. Analysis of anti-fungal properties of plant metabolites can lead to the development of more resistant wheat varieties while showing novel application of cheminformatics approaches in the analysis of plant/pathogen interactions. PMID:27706030

Left inferior-parietal lobe activity in perspective tasks: identity statements

PubMed Central

Arora, Aditi; Weiss, Benjamin; Schurz, Matthias; Aichhorn, Markus; Wieshofer, Rebecca C.; Perner, Josef

2015-01-01

We investigate the theory that the left inferior parietal lobe (IPL) is closely associated with tracking potential differences of perspective. Developmental studies find that perspective tasks are mastered at around 4 years of age. Our first study, meta-analyses of brain imaging studies shows that perspective tasks specifically activate a region in the left IPL and precuneus. These tasks include processing of false belief, visual perspective, and episodic memory. We test the location specificity theory in our second study with an unusual and novel kind of perspective task: identity statements. According to Frege's classical logical analysis, identity statements require appreciation of modes of presentation (perspectives). We show that identity statements, e.g., “the tour guide is also the driver” activate the left IPL in contrast to a control statements, “the tour guide has an apprentice.” This activation overlaps with the activations found in the meta-analysis. This finding is confirmed in a third study with different types of statements and different comparisons. All studies support the theory that the left IPL has as one of its overarching functions the tracking of perspective differences. We discuss how this function relates to the bottom-up attention function proposed for the bilateral IPL. PMID:26175677

Spanish adaptation of the internal functioning of the Work Teams Scale (QFI-22).

PubMed

Ficapal-Cusí, Pilar; Boada-Grau, Joan; Torrent-Sellens, Joan; Vigil-Colet, Andreu

2014-05-01

The aim of this article is to develop the Spanish adaptation of the internal functioning of Work Teams Scale (QFI-22). The scale was adapted from the French version, and was applied to a sample of 1,055 employees working for firms operating in Spain. The article analyses the internal structure (exploratory and confirmatory factor analysis) and internal consistency, and provides convergent validity evidence of the scale. The QFI-22 scale shows the same internal structure as the original. Factor analysis confirmed the existence of two factors: interpersonal support and team work management, with good internal consistency coefficients (α1 = .93, α2 = .92). Regarding validity evidence, the QFI-22 scale has significant correlations with other correlates and alternative scales used for comparison purposes. The two factors correlated positively with team vision, participation safety, task orientation and support for innovation (Team Climate Inventory, TCI scale), with progressive culture (Organisational Culture, X-Y scale), and with creating change, customer focus and organisational learning (Denison Organizational Culture Survey, DOCS scale). In contrast, the two factors correlated negatively with traditional culture (X-Y scale). The QFI-22 scale is a useful instrument for assessing the internal functioning of work teams.

Structural and Functional Survey of Environmental Aminoglycoside Acetyltransferases Reveals Functionality of Resistance Enzymes.

PubMed

Xu, Zhiyu; Stogios, Peter J; Quaile, Andrew T; Forsberg, Kevin J; Patel, Sanket; Skarina, Tatiana; Houliston, Scott; Arrowsmith, Cheryl; Dantas, Gautam; Savchenko, Alexei

2017-09-08

Aminoglycoside N-acetyltransferases (AACs) confer resistance against the clinical use of aminoglycoside antibiotics. The origin of AACs can be traced to environmental microbial species representing a vast reservoir for new and emerging resistance enzymes, which are currently undercharacterized. Here, we performed detailed structural characterization and functional analyses of four metagenomic AAC (meta-AACs) enzymes recently identified in a survey of agricultural and grassland soil microbiomes ( Forsberg et al. Nature 2014 , 509 , 612 ). These enzymes are new members of the Gcn5-Related-N-Acetyltransferase superfamily and confer resistance to the aminoglycosides gentamicin C, sisomicin, and tobramycin. Moreover, the meta-AAC0020 enzyme demonstrated activity comparable with an AAC(3)-I enzyme that serves as a model AAC enzyme identified in a clinical bacterial isolate. The crystal structure of meta-AAC0020 in complex with sisomicin confirmed an unexpected AAC(6') regiospecificity of this enzyme and revealed a drug binding mechanism distinct from previously characterized AAC(6') enzymes. Together, our data highlights the presence of highly active antibiotic-modifying enzymes in the environmental microbiome and reveals unexpected diversity in substrate specificity. These observations of additional AAC enzymes must be considered in the search for novel aminoglycosides less prone to resistance.

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

Duplicate retention in signalling proteins and constraints from network dynamics.

PubMed

Soyer, O S; Creevey, C J

2010-11-01

Duplications are a major driving force behind evolution. Most duplicates are believed to fix through genetic drift, but it is not clear whether this process affects all duplications equally or whether there are certain gene families that are expected to show neutral expansions under certain circumstances. Here, we analyse the neutrality of duplications in different functional classes of signalling proteins based on their effects on response dynamics. We find that duplications involving intermediary proteins in a signalling network are neutral more often than those involving receptors. Although the fraction of neutral duplications in all functional classes increase with decreasing population size and selective pressure on dynamics, this effect is most pronounced for receptors, indicating a possible expansion of receptors in species with small population size. In line with such an expectation, we found a statistically significant increase in the number of receptors as a fraction of genome size in eukaryotes compared with prokaryotes. Although not confirmative, these results indicate that neutral processes can be a significant factor in shaping signalling networks and affect proteins from different functional classes differently. © 2010 The Authors. Journal Compilation © 2010 European Society For Evolutionary Biology.

The neural substrates of action identification.

PubMed

Marsh, Abigail A; Kozak, Megan N; Wegner, Daniel M; Reid, Marguerite E; Yu, Henry H; Blair, R J R

2010-12-01

Mentalization is the process by which an observer views a target as possessing higher cognitive faculties such as goals, intentions and desires. Mentalization can be assessed using action identification paradigms, in which observers choose mentalistic (goals-focused) or mechanistic (action-focused) descriptions of targets' actions. Neural structures that play key roles in inferring goals and intentions from others' observed or imagined actions include temporo-parietal junction, ventral premotor cortex and extrastriate body area. We hypothesized that these regions play a role in action identification as well. Data collected using functional magnetic resonance imaging (fMRI) confirmed our predictions that activity in ventral premotor cortex and middle temporal gyrus near the extrastriate body area varies both as a function of the valence of the target and the extent to which actions are identified as goal-directed. In addition, the inferior parietal lobule is preferentially engaged when participants identify the actions of mentalized targets. Functional connectivity analyses suggest support from other regions, including the medial prefrontal cortex and amygdala, during mentalization. We found correlations between action identification and Autism Quotient scores, suggesting that understanding the neural correlates of action identification may enhance our understanding of the underpinnings of essential social cognitive processes.

Grammatical Analysis as a Distributed Neurobiological Function

PubMed Central

Bozic, Mirjana; Fonteneau, Elisabeth; Su, Li; Marslen-Wilson, William D

2015-01-01

Language processing engages large-scale functional networks in both hemispheres. Although it is widely accepted that left perisylvian regions have a key role in supporting complex grammatical computations, patient data suggest that some aspects of grammatical processing could be supported bilaterally. We investigated the distribution and the nature of grammatical computations across language processing networks by comparing two types of combinatorial grammatical sequences—inflectionally complex words and minimal phrases—and contrasting them with grammatically simple words. Novel multivariate analyses revealed that they engage a coalition of separable subsystems: inflected forms triggered left-lateralized activation, dissociable into dorsal processes supporting morphophonological parsing and ventral, lexically driven morphosyntactic processes. In contrast, simple phrases activated a consistently bilateral pattern of temporal regions, overlapping with inflectional activations in L middle temporal gyrus. These data confirm the role of the left-lateralized frontotemporal network in supporting complex grammatical computations. Critically, they also point to the capacity of bilateral temporal regions to support simple, linear grammatical computations. This is consistent with a dual neurobiological framework where phylogenetically older bihemispheric systems form part of the network that supports language function in the modern human, and where significant capacities for language comprehension remain intact even following severe left hemisphere damage. PMID:25421880

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Growth and characterization of Methyl 2-amino-5-bromobenzoate crystal for NLO applications

NASA Astrophysics Data System (ADS)

Parthasarathy, M.; Gopalakrishnan, R.

2012-11-01

Good quality single crystal of organic Methyl 2-amino-5-bromobenzoate (M2A5B) was grown using slow evaporation solution growth technique. The grown crystal was confirmed by single crystal X-ray diffraction. The functional groups and vibrational frequencies were identified using FT-IR and FT-Raman spectral analyses. The presence of hydrogen and carbon atoms in the grown sample was confirmed with proton and carbon NMR spectral studies. The optical energy band gap of the title compound is found to be 2.7 eV from the optical transmission spectra. The refractive indices nx, ny, and nz were found to be 1.569, 1.587 and 1.600, respectively using Brewster's angle method. The melting point of the material obtained with melting point apparatus is 74 °C. Thermal stability of the grown crystal was studied by thermogravimetric analysis (TGA) and differential thermal analysis (DTA). The mechanical behaviour of the grown crystal was analyzed with Vicker's microhardness tester. The particle size dependent second harmonic generation efficiency for M2A5B was evaluated by Kurtz-Perry powder method using Nd:YAG laser, which established the existence of phase matching.

Common Cutaneous Bacteria Isolated from Snakes Inhibit Growth of Ophidiomyces ophiodiicola.

PubMed

Hill, Aubree J; Leys, Jacob E; Bryan, Danny; Erdman, Fantasia M; Malone, Katherine S; Russell, Gabrielle N; Applegate, Roger D; Fenton, Heather; Niedringhaus, Kevin; Miller, Andrew N; Allender, Matthew C; Walker, Donald M

2018-03-01

There is increasing concern regarding potential impacts of snake fungal disease (SFD), caused by Ophidiomyces ophiodiicola (Oo), on free-ranging snake populations in the eastern USA. The snake cutaneous microbiome likely serves as the first line of defense against Oo and other pathogens; however, little is known about microbial associations in snakes. The objective of this study was to better define the composition and immune function of the snake cutaneous microbiome. Eight timber rattlesnakes (Crotalus horridus) and four black racers (Coluber constrictor) were captured in Arkansas and Tennessee, with some snakes exhibiting signs of SFD. Oo was detected through real-time qPCR in five snakes. Additional histopathological techniques confirmed a diagnosis of SFD in one racer, the species' first confirmed case of SFD in Tennessee. Fifty-eight bacterial and five fungal strains were isolated from skin swabs and identified with Sanger sequencing. Non-metric multidimensional scaling and PERMANOVA analyses indicated that the culturable microbiome does not differ between snake species. Fifteen bacterial strains isolated from rattlesnakes and a single strain isolated from a racer inhibited growth of Oo in vitro. Results shed light on the culturable cutaneous microbiome of snakes and probiotic members that may play a role in fighting an emergent disease.

Surface conjugation of poly (dimethyl siloxane) with itaconic acid-based materials for antibacterial effects

NASA Astrophysics Data System (ADS)

Birajdar, Mallinath S.; Cho, Hyunjoo; Seo, Youngmin; Choi, Jonghoon; Park, Hansoo

2018-04-01

Poly (dimethyl siloxane) (PDMS) is widely used in various biomedical applications. However, the PDMS surface is known to cause bacterial adhesion and protein absorption issues due to its high hydrophobicity. Therefore, the development of antibacterial and anti-protein products is necessary to prevent these problems. In this study, to improve its antibacterial property and prevent protein adsorption, PDMS surfaces were conjugated with itaconic acid (IA) and poly (itaconic acid) (PIA) via a chemical method. Additionally, IA and PIA were physically blended with PDMS to compare the antibacterial properties of these materials with those of the chemically conjugated PDMS surfaces. The successful synthesis of the PIA polymer structure was confirmed by proton nuclear magnetic resonance (1H NMR) spectroscopy. The successful conjugation of IA and PIA on PDMS was confirmed by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), water contact angle measurements, and microbicinchoninic acid (BCA) protein assay analyses. The PDMS surfaces functionalized with IA and PIA by the conjugation method better prevented protein adsorption than the bare PDMS. Therefore, these surface-conjugated PDMS can be used in various biomedical applications.

Thermograpic study of upper extremities in patients with cerebral palsy

NASA Astrophysics Data System (ADS)

Lampe, R.; Kawelke, S.; Mitternacht, J.; Turova, V.; Blumenstein, T.; Alves-Pinto, A.

2015-03-01

Trophic disorders like reduced skin blood circulation are well-known epiphenomenon of cerebral palsy (CP). They can influence quality of life and can lead to skin damages and, as a consequence, to decubitus. Therefore, it is important to analyse temperature regulation in patients with CP. Thermal imaging camera FLIR BCAM SD was used to study the dependency of skin blood circulation in upper extremities of patients with CP on hand dominance, hand force and hand volume. The hand force was evaluated using a conventional dynamometer. The hand volume was measured with a volumeter. A cold stress test for hands was applied in 22 patients with CP and 6 healthy subjects. The warming up process after the test was recorded with the thermal camera. It was confirmed that the hands of patients warm up slower comparing to healthy persons. The patients' working hands warm up faster than non-working ones. A slight correlation was established between the hand grip force of the working hands and their warm up time. No correlation was found between the warming up time and the volume of the hand. The results confirm our assumption that there is a connection of peripheral blood circulation to upper limb motor functions.

Identification of a candidate oncogene SEI-1 within a minimal amplified region at 19q13.1 in ovarian cancer cell lines.

PubMed

Tang, Terence C-M; Sham, Jonathan S T; Xie, Dan; Fang, Yan; Huo, Ke-Ke; Wu, Qiu-Liang; Guan, Xin-Yuan

2002-12-15

High-level amplification of DNA sequence at 19q13.1 is one of the frequent genetic alterations in ovarian cancer. In an attempt to verify the minimal amplified region (MAR) at 19q13.1 and to identify the target oncogenes, 49 probes within a region from D19S425 to D19S907 ( approximately 19.5 cM) were used to survey the amplification status in four ovarian cancer cell lines that have been confirmed as containing amplification at 19q13.1. Two separated overlapping MARs, MAR1 (approximately 200 kb) and MAR2 (approximately 1.1 Mb), were identified at 19q13.1. Two candidate oncogenes, AKT2 and SEI-1, were identified in MAR2. Amplification and overexpression of these two genes in four ovarian cancer cell lines were confirmed by Southern and Northern blot analyses. The proliferation-related function of AKT2 and SEI-1 suggests that both genes are likely to be biological targets of an amplification event at 19q13.1 in ovarian cancer and to play important roles in ovarian tumorigenesis.

Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia/small lymphocytic lymphoma: the InterLymph Non-Hodgkin Lymphoma Subtypes Project.

PubMed

Slager, Susan L; Benavente, Yolanda; Blair, Aaron; Vermeulen, Roel; Cerhan, James R; Costantini, Adele Seniori; Monnereau, Alain; Nieters, Alexandra; Clavel, Jacqueline; Call, Timothy G; Maynadié, Marc; Lan, Qing; Clarke, Christina A; Lightfoot, Tracy; Norman, Aaron D; Sampson, Joshua N; Casabonne, Delphine; Cocco, Pierluigi; de Sanjosé, Silvia

2014-08-01

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are two subtypes of non-Hodgkin lymphoma. A number of studies have evaluated associations between risk factors and CLL/SLL risk. However, these associations remain inconsistent or lacked confirmation. This may be due, in part, to the inadequate sample size of CLL/SLL cases. We performed a pooled analysis of 2440 CLL/SLL cases and 15186 controls from 13 case-control studies from Europe, North America, and Australia. We evaluated associations of medical history, family history, lifestyle, and occupational risk factors with CLL/SLL risk. Multivariate logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). We confirmed prior inverse associations with any atopic condition and recreational sun exposure. We also confirmed prior elevated associations with usual adult height, hepatitis C virus seropositivity, living or working on a farm, and family history of any hematological malignancy. Novel associations were identified with hairdresser occupation (OR = 1.77, 95% CI = 1.05 to 2.98) and blood transfusion history (OR = 0.79, 95% CI = 0.66 to 0.94). We also found smoking to have modest protective effect (OR = 0.9, 95% CI = 0.81 to 0.99). All exposures showed evidence of independent effects. We have identified or confirmed several independent risk factors for CLL/SLL supporting a role for genetics (through family history), immune function (through allergy and sun), infection (through hepatitis C virus), and height, and other pathways of immune response. Given that CLL/SLL has more than 30 susceptibility loci identified to date, studies evaluating the interaction among genetic and nongenetic factors are warranted. Published by Oxford University Press 2014.

Effect of solvents on optical band gap of silicon-doped graphene oxide

NASA Astrophysics Data System (ADS)

Tul Ain, Qura; Al-Modlej, Abeer; Alshammari, Abeer; Naeem Anjum, Muhammad

2018-03-01

The objective of this study was to determine the influence on the optical band gap when the same amount of silicon-doped graphene oxide was dissolved in three different solvents namely, distilled water, benzene, and dichloroethane. Ultraviolet-visible spectroscopy was used to analyse the optical properties of the solutions. Among all these solutions distilled water containing silicon-doped graphene oxide has the smallest optical band gap of 2.9 eV and is considered a semiconductor. Other solutions are not considered as semiconductors as they have optical band gaps greater than 4 eV. It was observed that there is an increase in the value of optical band gap of distilled water, benzene, and dichloroethane solutions indicating a rise in the insulating behaviour. In this experiment, graphene oxide was synthesised from graphite powder by modified Hummer’s method and was then doped with silicon. Synthesis and doping of graphene oxide were confirmed by various characterization techniques. Fourier transmission infrared spectroscopy was used for identification of surface functional groups. X-ray diffraction was carried out to confirm the formation of crystalline graphene oxide and silicon doped graphene oxide. In x-ray diffraction pattern, shifting of intensity peak from a 2θ value of 26.5° to 10° confirmed the synthesis of graphene oxide and various intensity peaks at different values of 2θ confirmed doping of graphene oxide with silicon. Scanning electron microscopy images indicated that graphene oxide sheets were decorated with spherical silicon nanoparticles. Energy dispersive x-ray spectroscopy showed that silicon doped graphene oxide powder contained 63.36% carbon, 34.05% oxygen, and 2.6% silicon.

Specific targeting and noninvasive magnetic resonance imaging of an asthma biomarker in the lung using polyethylene glycol functionalized magnetic nanocarriers.

PubMed

Al Faraj, Achraf; Shaik, Asma Sultana; Afzal, Sibtain; Al-Muhsen, Saleh; Halwani, Rabih

2016-05-01

Simultaneous inhibition of IL4 and IL13 via the common receptor chain IL4Rα to block adequately their biologic effects presents a promising therapeutic approach to give the additional relief required for asthma patients. In this study, superparamagnetic iron oxide nanoparticles were conjugated with anti-IL4Rα blocking antibodies via polyethylene glycol (PEG) polymers. The delivery of these blocking antibodies to the inflammatory sites in the lung via the developed nanocarriers was assessed using noninvasive free-breathing pulmonary MRI. Biocompatibility assays confirmed the safety of the developed nanocarriers for pre-clinical investigations. For all the investigated formulations, nanocarriers were found to be very stable at neutral pH. However, the stability noticeably decreased with the PEG length in acidic environment and thus the loaded antibodies were preferentially released. Immunofluorescence and fluorimetry assays confirmed the binding of the nanocarriers to the IL4Rα asthma biomarker. Pulmonary MRI performed using an ultra-short echo time sequence allowed simultaneous noninvasive monitoring of inflammatory responses induced by ovalbumin challenge and tracking of the developed nanocarriers, which were found to colocalize with the inflammatory sites in the lung. Targeting of the developed nanocarriers to areas rich in IL4Rα positive inflammatory cells was confirmed using histological and flow cytometry analyses. The anti-IL4Rα-conjugated nanocarriers developed here have been confirmed to be efficient in targeting key inflammatory cells during chronic lung inflammation following intrapulmonary administration. Targeting efficiency was monitored using noninvasive MRI, allowing detection of the nanocarriers' colocalizations with the inflammatory sites in the lung of ovalbumin-challenged asthmatic mice. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations.

PubMed

Philibert, Robert A; Beach, Steven R H; Gunter, Tracy D; Todorov, Alexandre A; Brody, Gene H; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-07-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1,555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime MD and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone, free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3'UTR of DIO1 (rs11206244), were associated with altered FT4 levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. Copyright © 2011 Wiley-Liss, Inc.

The Relationship of Deiodinase 1 Genotype and Thyroid Function to Lifetime History of Major Depression in Three Independent Populations

PubMed Central

Philibert, Robert A.; Beach, Steven R. H.; Gunter, Tracy D.; Todorov, Alexandre A.; Brody, Gene H.; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-01-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime major depression and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone (TSH), free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3’ UTR of DIO1 (rs11206244), were associated with altered free thyroxine (FT4) levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. PMID:21563302

Application of micro-X-ray fluorescence to chemical mapping of polar ice

NASA Astrophysics Data System (ADS)

Fourcade, M. C. Morel; Barnola, J. M.; Susini, J.; Baker, R.; Durand, G.; de Angelis, M.; Duval, P.

Synchrotron-based micro-X-ray fluorescence (μXRF) equipment has been used to analyze impurities in polar ice. A customized sample holder has been developed and the μXRF equipment has been adapted with a thermal control system to keep samples unaltered during analyses. Artificial ice samples prepared from ultra-pure water were analyzed to investigate possible contamination and/or experimental artefacts. Analyses of polar ice from Antarctica (Dome C and Vostok) confirm this μXRF technique is non-destructive and sensitive. Experiments can be reproduced to confirm or refine results by focusing on interesting spots such as crystal grain boundaries or specific inclusions. Integration times and resolution can be adjusted to optimize sensitivity. Investigation of unstable particles is possible due to the short analysis time. In addition to identification of elements in impurities, μXRF is able to determine their speciations. The accuracy and reliability of the results confirm the potential of this technique for research in glaciology.

Growth and dielectric, mechanical, thermal and etching studies of an organic nonlinear optical L-arginine trifluoroacetate (LATF) single crystal

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

Arjunan, S.; Department of Physics, Presidency College, Chennai 600005; Mohan Kumar, R.

2008-08-04

L-arginine trifluoroacetate, an organic nonlinear optical material, has been synthesized from aqueous solution. Bulk single crystal of dimension 57 mm x 5 mm x 3 mm has been grown by temperature lowering technique. Powder X-ray diffraction studies confirmed the monoclinic structure of the grown L-arginine trifluoroacetate crystal. Linear optical property of the grown crystal has been studied by UV-vis spectrum. Dielectric response of the L-arginine trifluoroacetate crystal was analysed for different frequencies and temperatures in detail. Microhardness study on the sample reveals that the crystal possesses relatively higher hardness compared to many organic crystals. Thermal analyses confirmed that the L-argininemore » trifluoroacetate material is thermally stable upto 212 deg. C. The etching studies have been performed to assess the perfection of the L-arginine trifluoroacetate crystal. Kurtz powder second harmonic generation test confirms the nonlinear optical properties of the as-grown L-arginine trifluoroacetate crystal.« less

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

OSIRIS-REx Asteroid Sample Return Mission Image Analysis

NASA Astrophysics Data System (ADS)

Chevres Fernandez, Lee Roger; Bos, Brent

2018-01-01

NASA’s Origins Spectral Interpretation Resource Identification Security-Regolith Explorer (OSIRIS-REx) mission constitutes the “first-of-its-kind” project to thoroughly characterize a near-Earth asteroid. The selected asteroid is (101955) 1999 RQ36 (a.k.a. Bennu). The mission launched in September 2016, and the spacecraft will reach its asteroid target in 2018 and return a sample to Earth in 2023. The spacecraft that will travel to, and collect a sample from, Bennu has five integrated instruments from national and international partners. NASA's OSIRIS-REx asteroid sample return mission spacecraft includes the Touch-And-Go Camera System (TAGCAMS) three camera-head instrument. The purpose of TAGCAMS is to provide imagery during the mission to facilitate navigation to the target asteroid, confirm acquisition of the asteroid sample and document asteroid sample stowage. Two of the TAGCAMS cameras, NavCam 1 and NavCam 2, serve as fully redundant navigation cameras to support optical navigation and natural feature tracking. The third TAGCAMS camera, StowCam, provides imagery to assist with and confirm proper stowage of the asteroid sample. Analysis of spacecraft imagery acquired by the TAGCAMS during cruise to the target asteroid Bennu was performed using custom codes developed in MATLAB. Assessment of the TAGCAMS in-flight performance using flight imagery was done to characterize camera performance. One specific area of investigation that was targeted was bad pixel mapping. A recent phase of the mission, known as the Earth Gravity Assist (EGA) maneuver, provided images that were used for the detection and confirmation of “questionable” pixels, possibly under responsive, using image segmentation analysis. Ongoing work on point spread function morphology and camera linearity and responsivity will also be used for calibration purposes and further analysis in preparation for proximity operations around Bennu. Said analyses will provide a broader understanding regarding the functionality of the camera system, which will in turn aid in the fly-down to the asteroid, as it will allow the pick of a suitable landing and sample location.

Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction.

PubMed

Kiss, Márton; Kiss, András A; Radics, Monika; Popovics, Nikoletta; Hermesz, Edit; Csiszár, Katalin; Mink, Mátyás

2016-01-01

The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that aberrant structure and function of the COL4A1 protein may also be a significant factor in modulating immunity.

Validation of heart failure diagnosis registered in primary care records in two primary care centres in Barcelona (Spain) and factors related. A cross-sectional study

PubMed Central

Verdú-Rotellar, Jose María; Frigola-Capell, Eva; Alvarez-Pérez, Rosa; da Silva, Daniela; Enjuanes, Cristina; Domingo, Mar; Mena, Amparo; Muñoz, Miguel-Angel

2017-01-01

Abstract Background: Heart failure (HF) diagnosis as reported in primary care medical records is not always properly confirmed and could result in over-registration. Objectives: To determine the proportion of registered HF that can be confirmed with information from primary care medical records and to analyse related factors. Methods: A cross-sectional study. The medical records of 595 HF patients attended in two primary healthcare centres in Barcelona (Spain) were revised and validated by a team of experts who classified diagnosis into confirmed, unconfirmed, and misdiagnosis. Variables potentially related to the confirmation of the diagnosis were analysed. The revision of medical records and data collection took place from 15 January to 31 March 2014. Results: Mean (standard deviation) age was 78 (10) years and 58% were women. The diagnosis could be confirmed in 53.6% of patients. Factors associated with a greater probability of having a confirmed diagnosis were age (yearly OR: 0.97, 95%CI: 0.95–0.99), cardiologist follow-up (OR: 3.66, 95%CI: 2.46–5.48), history of ischaemic heart disease (OR: 2.18, 95%CI: 1.36–2.48), atrial fibrillation (OR: 2.01, 95%CI: 1.34–3.03), and prescription of loop diuretics (OR: 3.24, 95%CI: 2.14–4.89). Conclusion: Only in half of the patients labelled as HF in primary care medical records could this diagnosis be further confirmed. Variables regularly registered in clinical practice could help general practitioners identify those patients requiring a revision of their HF diagnosis. PMID:28376668

Synthesis, growth, structural, optical, spectral, thermal and mechanical studies of 4-methoxy 4-nitrostilbene (MONS): a new organic nonlinear optical single crystal.

PubMed

Dinakaran, Paul M; Bhagavannarayana, G; Kalainathan, S

2012-11-01

4-Methoxy 4-nitrostilbene (MONS), a new organic nonlinear optical material has been synthesized. Based on the solubility data good quality single crystal with dimensions up to 38×11×3 mm(3) has been grown by slow evaporation method using ethyl methyl ketone (MEK) as a solvent. Powder XRD confirms the crystalline property and also the diffraction planes have been indexed. The lattice parameters for the grown MONS crystals were determined by using single crystal X-ray diffraction analysis and it reveals that the crystal lattice system is triclinic. The crystalline perfection of the grown crystals has been analysed by high resolution X-ray diffraction (HRXRD) rocking curve measurements. Fourier transform infrared (FTIR) spectrum for powdered MONS sample confirms the functional groups present in the grown crystal. The UV-vis absorption spectrum has been recorded in the range of 190-1100 nm and the cut off wavelength 499 nm has been determined. The optical constants of MONS have been determined through UV-vis-NIR spectroscopy. The MONS crystals were further subjected to other characterizations. i.e., (1)H NMR, TG/DTA, photoluminescence and microhardness test. The Kurtz and Perry powder technique confirms the NLO property of the grown crystal and the SHG efficiency of MONS was found to be 1.55× greater than that of KDP crystal. Copyright © 2012 Elsevier B.V. All rights reserved.

Genome-wide Association Studies Identify Genetic Loci Associated With Albuminuria in Diabetes

PubMed Central

Tin, Adrienne; Sorice, Rossella; Gorski, Mathias; Yeo, Nan Cher; Chu, Audrey Y.; Li, Man; Li, Yong; Mijatovic, Vladan; Ko, Yi-An; Taliun, Daniel; Luciani, Alessandro; Chen, Ming-Huei; Yang, Qiong; Foster, Meredith C.; Olden, Matthias; Hiraki, Linda T.; Tayo, Bamidele O.; Fuchsberger, Christian; Dieffenbach, Aida Karina; Shuldiner, Alan R.; Smith, Albert V.; Zappa, Allison M.; Lupo, Antonio; Kollerits, Barbara; Ponte, Belen; Stengel, Bénédicte; Krämer, Bernhard K.; Paulweber, Bernhard; Mitchell, Braxton D.; Hayward, Caroline; Helmer, Catherine; Meisinger, Christa; Gieger, Christian; Shaffer, Christian M.; Müller, Christian; Langenberg, Claudia; Ackermann, Daniel; Siscovick, David; Boerwinkle, Eric; Kronenberg, Florian; Ehret, Georg B.; Homuth, Georg; Waeber, Gerard; Navis, Gerjan; Gambaro, Giovanni; Malerba, Giovanni; Eiriksdottir, Gudny; Li, Guo; Wichmann, H. Erich; Grallert, Harald; Wallaschofski, Henri; Völzke, Henry; Brenner, Herrmann; Kramer, Holly; Leach, I. Mateo; Rudan, Igor; Hillege, Hans L.; Beckmann, Jacques S.; Lambert, Jean Charles; Luan, Jian'an; Zhao, Jing Hua; Chalmers, John; Coresh, Josef; Denny, Joshua C.; Butterbach, Katja; Launer, Lenore J.; Ferrucci, Luigi; Kedenko, Lyudmyla; Haun, Margot; Metzger, Marie; Woodward, Mark; Hoffman, Matthew J.; Nauck, Matthias; Waldenberger, Melanie; Pruijm, Menno; Bochud, Murielle; Rheinberger, Myriam; Verweij, Niek; Wareham, Nicholas J.; Endlich, Nicole; Soranzo, Nicole; Polasek, Ozren; van der Harst, Pim; Pramstaller, Peter Paul; Vollenweider, Peter; Wild, Philipp S.; Gansevoort, Ron T.; Rettig, Rainer; Biffar, Reiner; Carroll, Robert J.; Katz, Ronit; Loos, Ruth J.F.; Hwang, Shih-Jen; Coassin, Stefan; Bergmann, Sven; Rosas, Sylvia E.; Stracke, Sylvia; Harris, Tamara B.; Corre, Tanguy; Zeller, Tanja; Illig, Thomas; Aspelund, Thor; Tanaka, Toshiko; Lendeckel, Uwe; Völker, Uwe; Gudnason, Vilmundur; Chouraki, Vincent; Koenig, Wolfgang; Kutalik, Zoltan; O'Connell, Jeffrey R.; Parsa, Afshin; Heid, Iris M.; Paterson, Andrew D.; de Boer, Ian H.; Devuyst, Olivier; Lazar, Jozef; Endlich, Karlhans; Susztak, Katalin; Tremblay, Johanne; Hamet, Pavel; Jacob, Howard J.; Böger, Carsten A.

2016-01-01

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were detected and confirmed for variants in HS6ST1 and near RAB38/CTSC. Single nucleotide polymorphisms at these loci demonstrated a genetic effect on UACR in individuals with but not without diabetes. The change in the average UACR per minor allele was 21% for HS6ST1 (P = 6.3 × 10–7) and 13% for RAB38/CTSC (P = 5.8 × 10−7). Experiments using streptozotocin-induced diabetic Rab38 knockout and control rats showed higher urinary albumin concentrations and reduced amounts of megalin and cubilin at the proximal tubule cell surface in Rab38 knockout versus control rats. Relative expression of RAB38 was higher in tubuli of patients with diabetic kidney disease compared with control subjects. The loci identified here confirm known pathways and highlight novel pathways influencing albuminuria. PMID:26631737

Confirmation and lucidity during conversations with a woman with severe dementia.

PubMed

Normann, Hans Ketil; Norberg, Astrid; Asplund, Kenneth

2002-08-01

Patients with severe dementia sometimes surprise the care providers because they seem to be much more aware of their situation and function much more adequately than usual. Such episodes are labelled 'episodes of lucidity' (ELs). The aim of this study was to describe the characteristics of the particular conversations with a woman with severe dementia when ELs occurred as compared with conversations when she was not lucid. A woman with a probable diagnosis of Alzheimer's disease (AD) was selected. Her Mini Mental State Examination (MMSE) was estimated as 3. The first author met the woman for 4 hours five times over a period of 2 weeks. RESEARCH ETHODS: The conversations were tape-recorded and transcribed verbatim. The text was divided into 278 content units and analysed. Lucidity is promoted by supporting the patient in various ways, that is sharing the patient's view, repeating and reformulating the patient's utterance, reinforcing the patient by using positive utterances, not emphasizing errors and supporting the patient's language in various ways, and avoiding making demands. The relation between the patient and her conversation partner during ELs is characterized by confirmation and communion. This case study indicates that a supportive attitude in conversation with the patient with severe dementia promotes lucidity. A supportive attitude includes the avoidance on the part of the conversational partner making demands on the patient, confirming the patient as an important, unique and valuable person and creating communion. The connection between supporting and avoiding demands and lucidity/nonlucidity during conversation needs further study.

Growth, spectral, thermal, laser damage threshold, microhardness, dielectric, linear and nonlinear optical properties of an organic single crystal: L-phenylalanine DL-mandelic acid

NASA Astrophysics Data System (ADS)

Jayaprakash, P.; Peer Mohamed, M.; Krishnan, P.; Nageshwari, M.; Mani, G.; Lydia Caroline, M.

2016-12-01

Single crystals of L-phenylalanine dl-mandelic acid [C9H11NO2. C8H8O3], have been grown by the slow evaporation technique at room temperature using aqueous solution. The single crystal XRD study confirms monoclinic system for the grown crystal. The functional groups present in the grown crystal have been identified by FTIR and FT-Raman analyses. The optical absorption studies show that the crystal is transparent in the visible region with a lower cut-off wavelength of 257 nm and the optical band gap energy Eg is determined to be 4.62 eV. The Kurtz powder second harmonic generation was confirmed using Nd:YAG laser with fundamental wavelength of 1064 nm. Further, the thermal studies confirmed no weight loss up to 150°C for the as-grown crystal. The photoluminescence spectrum exhibited three peaks (414 nm, 519 nm, 568 nm) due to the donation of protons from carboxylic acid to amino group. Laser damage threshold value was found to be 4.98 GW/cm2. The Vickers microhardness test was carried out on the grown crystals and there by Vickers hardness number (Hv), work hardening coefficient (n), yield strength (σy), stiffness constant C11 were evaluated. The dielectric behavior of the crystal has been determined in the frequency range 50 Hz-5 MHz at various temperatures.

Examining the Relationship between Gender and Drug-Using Behaviors in Adolescents: The Use of Diagnostic Assessments and Biochemical Analyses of Urine Samples.

ERIC Educational Resources Information Center

James, William H.; Moore, David D.

1999-01-01

Examines the relationship between gender and drug use among adolescents using diagnostic assessments and biochemical analyses of urine samples. Statistical significance was found in the relationship between gender and marijuana use. The study confirms that more research is needed in this area. (Author/MKA)

Identification of potential crucial genes associated with steroid-induced necrosis of femoral head based on gene expression profile.

PubMed

Lin, Zhe; Lin, Yongsheng

2017-09-05

The aim of this study was to explore potential crucial genes associated with the steroid-induced necrosis of femoral head (SINFH) and to provide valid biological information for further investigation of SINFH. Gene expression profile of GSE26316, generated from 3 SINFH rat samples and 3 normal rat samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified using LIMMA package. After functional enrichment analyses of DEGs, protein-protein interaction (PPI) network and sub-PPI network analyses were conducted based on the STRING database and cytoscape. In total, 59 up-regulated DEGs and 156 downregulated DEGs were identified. The up-regulated DEGs were mainly involved in functions about immunity (e.g. Fcer1A and Il7R), and the downregulated DEGs were mainly enriched in muscle system process (e.g. Tnni2, Mylpf and Myl1). The PPI network of DEGs consisted of 123 nodes and 300 interactions. Tnni2, Mylpf, and Myl1 were the top 3 outstanding genes based on both subgraph centrality and degree centrality evaluation. These three genes interacted with each other in the network. Furthermore, the significant network module was composed of 22 downregulated genes (e.g. Tnni2, Mylpf and Myl1). These genes were mainly enriched in functions like muscle system process. The DEGs related to the regulation of immune system process (e.g. Fcer1A and Il7R), and DEGs correlated with muscle system process (e.g. Tnni2, Mylpf and Myl1) may be closely associated with the progress of SINFH, which is still needed to be confirmed by experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Heterogeneity of p53 dependent genomic responses following ethanol exposure in a developmental mouse model of fetal alcohol spectrum disorder

PubMed Central

Mooney, Sandra M.; Middleton, Frank A.

2017-01-01

Prenatal ethanol exposure can produce structural and functional deficits in the brain and result in Fetal Alcohol Spectrum Disorder (FASD). In rodent models acute exposure to a high concentration of alcohol causes increased apoptosis in the developing brain. A single causal molecular switch that signals for this increase in apoptosis has yet to be identified. The protein p53 has been suggested to play a pivotal role in enabling cells to engage in pro-apoptotic processes, and thus figures prominently as a hub molecule in the intracellular cascade of responses elicited by alcohol exposure. In the present study we examined the effect of ethanol-induced cellular and molecular responses in primary somatosensory cortex (SI) and hippocampus of 7-day-old wild-type (WT) and p53-knockout (KO) mice. We quantified apoptosis by active caspase-3 immunohistochemistry and ApopTag™ labeling, then determined total RNA expression levels in laminae of SI and hippocampal subregions. Immunohistochemical results confirmed increased incidence of apoptotic cells in both regions in WT and KO mice following ethanol exposure. The lack of p53 was not protective in these brain regions. Molecular analyses revealed a heterogeneous response to ethanol exposure that varied depending on the subregion, and which may go undetected using a global approach. Gene network analyses suggest that the presence or absence of p53 alters neuronal function and synaptic modifications following ethanol exposure, in addition to playing a classic role in cell cycle signaling. Thus, p53 may function in a way that underlies the intellectual and behavioral deficits observed in FASD. PMID:28723918

Use of Oral Bisphosphonates by Older Adults with Fractures and Impaired Renal Function

PubMed Central

Sadowski, Cheryl A; Spencer, Tara; Yuksel, Nese

2011-01-01

Background: The manufacturers of oral bisphosphonates (alendronate, risedronate) recommend avoiding use of these drugs in patients with renal impairment. However, many patients who have osteoporosis or who are at risk of fracture are elderly and may have renal impairment. This situation poses a quandary for clinicians in deciding how best to manage osteoporosis in this high-risk population. Objective: To synthesize published evidence regarding the use and safety of oral bisphosphonates for patients with impaired renal function. Methods: The following databases were searched up to October 2010: PubMed, MEDLINE, Embase, the Cochrane Library, and International Pharmaceutical Abstracts. The following key words and terms were used for the searches: bisphosphonates, alendronate, risedronate, Fosamax, Actonel, “renal failure”, “renal insufficiency”, “chronic kidney disease”, and “end-stage renal disease”. The manufacturers of Fosamax and Actonel were asked to provide information about use of their products in patients with renal impairment, including unpublished pharmacokinetic studies or reports of adverse drug events. Results: The search yielded 2 post hoc analyses of safety data, 1 case–control study, 1 case series, 4 retrospective chart analyses, and 2 prospective studies. According to these publications, numerous patients with decreased renal function have received bisphosphonates and have experienced improvement in bone mineral density and/or reduction in risk of fractures, with no increase in adverse effects. Increased renal damage occurred in some individuals with underlying renal disorders, as described in case reports. Conclusions: Although the literature is limited, there is evidence that alendronate and risedronate are well tolerated and effective when used by individuals with renal impairment. Further research is required to confirm the benefits and risks of using these medications in patients with renal impairment. PMID:22479027

Association between autism symptoms and family functioning in children with attention-deficit/hyperactivity disorder: a community-based study.

PubMed

Green, Jessica L; Rinehart, Nicole; Anderson, Vicki; Efron, Daryl; Nicholson, Jan M; Jongeling, Brad; Hazell, Philip; Sciberras, Emma

2016-12-01

Autism spectrum disorder (ASD) symptoms are elevated in populations of children with attention-deficit/hyperactivity disorder (ADHD). This study examined cross-sectional associations between ASD symptoms and family functioning in children with and without ADHD. Participants were recruited to a longitudinal cohort study, aged 6-10 years (164 ADHD; 198 controls). ADHD cases were ascertained using community-based screening and diagnostic confirmation from a diagnostic interview. ASD symptoms were measured using the Social Communication Questionnaire. Outcome variables were parent mental health, family quality of life (FQoL), couple conflict and support, and parenting behaviours. After adjustment for a range of child and family factors (including other mental health comorbidities), higher ASD symptoms were associated with poorer FQoL across all three domains; emotional impact (p = 0.008), family impact (p = 0.001) and time impact (p = 0.003). In adjusted analyses by subgroup, parents of children with ADHD+ASD had poorer parent self-efficacy (p = 0.01), poorer FQoL (p ≤ 0.05), with weak evidence of an association for less couple support (p = 0.06), compared to parents of children with ADHD only. Inspection of covariates in the adjusted analyses indicated that the association between ASD symptoms and most family functioning measures was accounted forby child internalising and externalising disorders, ADHD severity, and socioeconomic status; however, ASD symptoms appear to be independently associated with poorer FQoL in children with ADHD. The presence of ASD symptoms in children with ADHD may signal the need for enhanced family support.

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

Genomic features separating ten strains of Neorhizobium galegae with different symbiotic phenotypes.

PubMed

Österman, Janina; Mousavi, Seyed Abdollah; Koskinen, Patrik; Paulin, Lars; Lindström, Kristina

2015-05-02

The symbiotic phenotype of Neorhizobium galegae, with strains specifically fixing nitrogen with either Galega orientalis or G. officinalis, has made it a target in research on determinants of host specificity in nitrogen fixation. The genomic differences between representative strains of the two symbiovars are, however, relatively small. This introduced a need for a dataset representing a larger bacterial population in order to make better conclusions on characteristics typical for a subset of the species. In this study, we produced draft genomes of eight strains of N. galegae having different symbiotic phenotypes, both with regard to host specificity and nitrogen fixation efficiency. These genomes were analysed together with the previously published complete genomes of N. galegae strains HAMBI 540T and HAMBI 1141. The results showed that the presence of an additional rpoN sigma factor gene in the symbiosis gene region is a characteristic specific to symbiovar orientalis, required for nitrogen fixation. Also the nifQ gene was shown to be crucial for functional symbiosis in both symbiovars. Genome-wide analyses identified additional genes characteristic of strains of the same symbiovar and of strains having similar plant growth promoting properties on Galega orientalis. Many of these genes are involved in transcriptional regulation or in metabolic functions. The results of this study confirm that the only symbiosis-related gene that is present in one symbiovar of N. galegae but not in the other is an rpoN gene. The specific function of this gene remains to be determined, however. New genes that were identified as specific for strains of one symbiovar may be involved in determining host specificity, while others are defined as potential determinant genes for differences in efficiency of nitrogen fixation.

Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials.

PubMed

Diaz-Manera, Jordi; Fernandez-Torron, Roberto; LLauger, Jaume; James, Meredith K; Mayhew, Anna; Smith, Fiona E; Moore, Ursula R; Blamire, Andrew M; Carlier, Pierre G; Rufibach, Laura; Mittal, Plavi; Eagle, Michelle; Jacobs, Marni; Hodgson, Tim; Wallace, Dorothy; Ward, Louise; Smith, Mark; Stramare, Roberto; Rampado, Alessandro; Sato, Noriko; Tamaru, Takeshi; Harwick, Bruce; Rico Gala, Susana; Turk, Suna; Coppenrath, Eva M; Foster, Glenn; Bendahan, David; Le Fur, Yann; Fricke, Stanley T; Otero, Hansel; Foster, Sheryl L; Peduto, Anthony; Sawyer, Anne Marie; Hilsden, Heather; Lochmuller, Hanns; Grieben, Ulrike; Spuler, Simone; Tesi Rocha, Carolina; Day, John W; Jones, Kristi J; Bharucha-Goebel, Diana X; Salort-Campana, Emmanuelle; Harms, Matthew; Pestronk, Alan; Krause, Sabine; Schreiber-Katz, Olivia; Walter, Maggie C; Paradas, Carmen; Hogrel, Jean-Yves; Stojkovic, Tanya; Takeda, Shin'ichi; Mori-Yoshimura, Madoka; Bravver, Elena; Sparks, Susan; Bello, Luca; Semplicini, Claudio; Pegoraro, Elena; Mendell, Jerry R; Bushby, Kate; Straub, Volker

2018-05-07

Dysferlinopathies are a group of muscle disorders caused by mutations in the DYSF gene. Previous muscle imaging studies describe a selective pattern of muscle involvement in smaller patient cohorts, but a large imaging study across the entire spectrum of the dysferlinopathies had not been performed and previous imaging findings were not correlated with functional tests. We present cross-sectional T1-weighted muscle MRI data from 182 patients with genetically confirmed dysferlinopathies. We have analysed the pattern of muscles involved in the disease using hierarchical analysis and presented it as heatmaps. Results of the MRI scans have been correlated with relevant functional tests for each region of the body analysed. In 181 of the 182 patients scanned, we observed muscle pathology on T1-weighted images, with the gastrocnemius medialis and the soleus being the most commonly affected muscles. A similar pattern of involvement was identified in most patients regardless of their clinical presentation. Increased muscle pathology on MRI correlated positively with disease duration and functional impairment. The information generated by this study is of high diagnostic value and important for clinical trial development. We have been able to describe a pattern that can be considered as characteristic of dysferlinopathy. We have defined the natural history of the disease from a radiological point of view. These results enabled the identification of the most relevant regions of interest for quantitative MRI in longitudinal studies, such as clinical trials. NCT01676077. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis.

PubMed

Takei, Koji; Takahashi, Fumihiro; Liu, Shawn; Tsuda, Kikumi; Palumbo, Joseph

2017-10-01

Post-hoc analyses of the ALS Functional Rating Scale-Revised (ALSFRS-R) score data, the primary endpoint in the 24-week double-blind placebo-controlled study of edaravone (MCI186-19, NCT01492686), were performed to confirm statistical robustness of the result. The previously reported original analysis had used a last observation carried forward (LOCF) method and also excluded patients with fewer than three completed treatment cycles. The post-hoc sensitivity analyses used different statistical methods as follows: 1) including all patients regardless of treatment cycles received (ALL LOCF); 2) a mixed model for repeated measurements (MMRM) analysis; and 3) the Combined Assessment of Function and Survival (CAFS) endpoint. Findings were consistent with the original primary analysis in showing superiority of edaravone over placebo. We also investigated the distribution of change in ALSFRS-R total score across all patients in the study as well as which ALSFRS-R items and domains may have contributed to the overall efficacy findings. The distribution of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF) shifted in favour of edaravone compared to placebo. Edaravone was descriptively favoured for each ALSFRS-R item and each of the four ALSFRS-R domains at the end of cycle 6 (ALL LOCF), suggesting a generalised effect of edaravone in slowing functional decline across all anatomical regions. The effect of edaravone appeared to be similar in patients with bulbar onset and limb onset. Together, these observations would be consistent with its putative neuroprotective effects against the development of oxidative damage unspecific to anatomical regions.

Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

PubMed Central

Wu, Ying; Waite, Lindsay L.; Jackson, Anne U.; Sheu, Wayne H-H.; Buyske, Steven; Absher, Devin; Arnett, Donna K.; Boerwinkle, Eric; Bonnycastle, Lori L.; Carty, Cara L.; Cheng, Iona; Cochran, Barbara; Croteau-Chonka, Damien C.; Dumitrescu, Logan; Eaton, Charles B.; Franceschini, Nora; Guo, Xiuqing; Henderson, Brian E.; Hindorff, Lucia A.; Kim, Eric; Kinnunen, Leena; Komulainen, Pirjo; Lee, Wen-Jane; Le Marchand, Loic; Lin, Yi; Lindström, Jaana; Lingaas-Holmen, Oddgeir; Mitchell, Sabrina L.; Narisu, Narisu; Robinson, Jennifer G.; Schumacher, Fred; Stančáková, Alena; Sundvall, Jouko; Sung, Yun-Ju; Swift, Amy J.; Wang, Wen-Chang; Wilkens, Lynne; Wilsgaard, Tom; Young, Alicia M.; Adair, Linda S.; Ballantyne, Christie M.; Bůžková, Petra; Chakravarti, Aravinda; Collins, Francis S.; Duggan, David; Feranil, Alan B.; Ho, Low-Tone; Hung, Yi-Jen; Hunt, Steven C.; Hveem, Kristian; Juang, Jyh-Ming J.; Kesäniemi, Antero Y.; Kuusisto, Johanna; Laakso, Markku; Lakka, Timo A.; Lee, I-Te; Leppert, Mark F.; Matise, Tara C.; Moilanen, Leena; Njølstad, Inger; Peters, Ulrike; Quertermous, Thomas; Rauramaa, Rainer; Rotter, Jerome I.; Saramies, Jouko; Tuomilehto, Jaakko; Uusitupa, Matti; Wang, Tzung-Dau; Mohlke, Karen L.

2013-01-01

Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1×10−4 in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies. PMID:23555291

Association of persistent and transient worsening renal function with mortality risk, readmissions risk, length of stay, and costs in patients hospitalized with acute heart failure.

PubMed

Palmer, Jacqueline B; Friedman, Howard S; Waltman Johnson, Katherine; Navaratnam, Prakash; Gottlieb, Stephen S

2015-01-01

Data comparing effects of transient worsening renal function (WRFt) and persistent WRF (WRFp) on outcomes in patients hospitalized with acute heart failure (AHF) are lacking. We determined the characteristics of hospitalized AHF patients who experienced no worsening renal function (non-WRF), WRFt, or WRFp, and the relationship between cohorts and AHF-related outcomes. A patient's first AHF hospitalization (index) was identified in the Cerner Health Facts(®) database (January 2008-March 2011). Patients had WRF if serum creatinine (SCr) was ≥0.3 mg/dL and increased ≥25% from baseline, and they were designated as WRFp if present at discharge or WRFt if not present at discharge. A total of 55,436 patients were selected (non-WRF =77%, WRFp =10%, WRFt =13%). WRFp had greater comorbidity burden than WRFt. At index hospitalization, WRFp patients had the highest mortality, whereas WRFt patients had the longest length of stay (LOS) and highest costs. These trends were observed at 30, 180, and 365 days postdischarge and confirmed by multivariable analyses. WRF patients had more AHF-related readmissions than non-WRF patients. In sensitivity analyses of the patient subset with live index hospitalization discharges, postdischarge LOS and costs were highest in WRFt patients, whereas mortality associated with a HF hospitalization was significantly higher for WRF patients vs non-WRF patients, with no difference between WRFp and WRFt. In patients hospitalized for AHF, WRFp was associated with the highest mortality, whereas WRFt was associated with the highest LOS and costs. WRF patients had higher readmissions than non-WRF patients. Transient increases in SCr appear to be associated with detrimental outcomes, especially longer LOS and higher costs.

Association of persistent and transient worsening renal function with mortality risk, readmissions risk, length of stay, and costs in patients hospitalized with acute heart failure

PubMed Central

Palmer, Jacqueline B; Friedman, Howard S; Waltman Johnson, Katherine; Navaratnam, Prakash; Gottlieb, Stephen S

2015-01-01

Background Data comparing effects of transient worsening renal function (WRFt) and persistent WRF (WRFp) on outcomes in patients hospitalized with acute heart failure (AHF) are lacking. We determined the characteristics of hospitalized AHF patients who experienced no worsening renal function (non-WRF), WRFt, or WRFp, and the relationship between cohorts and AHF-related outcomes. Methods and results A patient’s first AHF hospitalization (index) was identified in the Cerner Health Facts® database (January 2008−March 2011). Patients had WRF if serum creatinine (SCr) was ≥0.3 mg/dL and increased ≥25% from baseline, and they were designated as WRFp if present at discharge or WRFt if not present at discharge. A total of 55,436 patients were selected (non-WRF =77%, WRFp =10%, WRFt =13%). WRFp had greater comorbidity burden than WRFt. At index hospitalization, WRFp patients had the highest mortality, whereas WRFt patients had the longest length of stay (LOS) and highest costs. These trends were observed at 30, 180, and 365 days postdischarge and confirmed by multivariable analyses. WRF patients had more AHF-related readmissions than non-WRF patients. In sensitivity analyses of the patient subset with live index hospitalization discharges, postdischarge LOS and costs were highest in WRFt patients, whereas mortality associated with a HF hospitalization was significantly higher for WRF patients vs non-WRF patients, with no difference between WRFp and WRFt. Conclusion In patients hospitalized for AHF, WRFp was associated with the highest mortality, whereas WRFt was associated with the highest LOS and costs. WRF patients had higher readmissions than non-WRF patients. Transient increases in SCr appear to be associated with detrimental outcomes, especially longer LOS and higher costs. PMID:26150730

Multi-level evaluation of Escherichia coli polyphosphate related mutants using global transcriptomic, proteomic and phenomic analyses.

PubMed

Varas, Macarena; Valdivieso, Camilo; Mauriaca, Cecilia; Ortíz-Severín, Javiera; Paradela, Alberto; Poblete-Castro, Ignacio; Cabrera, Ricardo; Chávez, Francisco P

2017-04-01

Polyphosphate (polyP) is a linear biopolymer found in all living cells. In bacteria, mutants lacking polyphosphate kinase 1 (PPK1), the enzyme responsible for synthesis of most polyP, have many structural and functional defects. However, little is known about the causes of these pleiotropic alterations. The link between ppk1 deletion and those numerous phenotypes observed can be the result of complex molecular interactions that can be elucidated via a systems biology approach. By integrating different omics levels (transcriptome, proteome and phenome), we described the functioning of various metabolic pathways among Escherichia coli polyphosphate mutant strains (Δppk1, Δppx, and ΔpolyP). Bioinformatic analyses reveal the complex metabolic and regulatory bases of the phenotypes unique to polyP mutants. Our results suggest that during polyP deficiency (Δppk1 mutant), metabolic pathways needed for energy supply are up-regulated, including fermentation, aerobic and anaerobic respiration. Transcriptomic and q-proteomic contrasting changes between Δppk1 and Δppx mutant strains were observed in those central metabolic pathways and confirmed by using Phenotypic microarrays. In addition, our results suggest a regulatory connection between polyP, second messenger metabolism, alternative Sigma/Anti-Sigma factors and type-II toxin-antitoxin (TA) systems. We suggest a broader role for polyP via regulation of ATP-dependent proteolysis of type II toxin-antitoxin system and alternative Sigma/Anti-Sigma factors, that could explain the multiple structural and functional deficiencies described due to alteration of polyP metabolism. Understanding the interplay of polyP in bacterial metabolism using a systems biology approach can help to improve design of novel antimicrobials toward pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Does physical exposure throughout working life influence chair-rise performance in midlife? A retrospective cohort study of associations between work and physical function in Denmark.

PubMed

Møller, Anne; Reventlow, Susanne; Hansen, Åse Marie; Andersen, Lars L; Siersma, Volkert; Lund, Rikke; Avlund, Kirsten; Andersen, Johan Hviid; Mortensen, Ole Steen

2015-11-04

Our aim was to study associations between physical exposures throughout working life and physical function measured as chair-rise performance in midlife. The Copenhagen Aging and Midlife Biobank (CAMB) provided data about employment and measures of physical function. Individual job histories were assigned exposures from a job exposure matrix. Exposures were standardised to ton-years (lifting 1000 kg each day in 1 year), stand-years (standing/walking for 6 h each day in 1 year) and kneel-years (kneeling for 1 h each day in 1 year). The associations between exposure-years and chair-rise performance (number of chair-rises in 30 s) were analysed in multivariate linear and non-linear regression models adjusted for covariates. Mean age among the 5095 participants was 59 years in both genders, and, on average, men achieved 21.58 (SD=5.60) and women 20.38 (SD=5.33) chair-rises in 30 s. Physical exposures were associated with poorer chair-rise performance in both men and women, however, only associations between lifting and standing/walking and chair-rise remained statistically significant among men in the final model. Spline regression analyses showed non-linear associations and confirmed the findings. Higher physical exposure throughout working life is associated with slightly poorer chair-rise performance. The associations between exposure and outcome were non-linear. 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/

Temporal expression profiles indicate a primary function for microRNA during the peak of DNA replication after rat partial hepatectomy.

PubMed

Raschzok, Nathanael; Werner, Wiebke; Sallmon, Hannes; Billecke, Nils; Dame, Christof; Neuhaus, Peter; Sauer, Igor M

2011-06-01

The liver has the unique capacity to regenerate after surgical resection. However, the regulation of liver regeneration is not completely understood. Recent reports indicate an essential role for small noncoding microRNAs (miRNAs) in the regulation of hepatic development, carcinogenesis, and early regeneration. We hypothesized that miRNAs are critically involved in all phases of liver regeneration after partial hepatectomy. We performed miRNA microarray analyses after 70% partial hepatectomy in rats under isoflurane anesthesia at different time points (0 h to 5 days) and after sham laparotomy. Putative targets of differentially expressed miRNAs were determined using a bioinformatic approach. Two-dimensional (2D)-PAGE proteomic analyses and protein identification were performed on specimens at 0 and 24 h after resection. The temporal dynamics of liver regeneration were characterized by 5-bromo- 2-deoxyuridine, proliferating cell nuclear antigen, IL-6, and hepatocyte growth factor. We demonstrate that miRNA expression patterns changed during liver regeneration and that these changes were most evident during the peak of DNA replication at 24 h after resection. Expression of 13 miRNAs was significantly reduced 12-48 h after resection (>25% change), out of which downreguation was confirmed in isolated hepatocytes for 6 miRNAs at 24 h, whereas three miRNAs were significantly upregulated. Proteomic analysis revealed 65 upregulated proteins; among them, 23 represent putative targets of the differentially expressed miRNAs. We provide a temporal miRNA expression and proteomic dataset of the regenerating rat liver, which indicates a primary function for miRNA during the peak of DNA replication. These data will assist further functional studies on the role of miRNAs during liver regeneration.

A phase coherence approach to identifying co-located earthquakes and tremor

NASA Astrophysics Data System (ADS)

Hawthorne, J. C.; Ampuero, J.-P.

2018-05-01

We present and use a phase coherence approach to identify seismic signals that have similar path effects but different source time functions: co-located earthquakes and tremor. The method used is a phase coherence-based implementation of empirical matched field processing, modified to suit tremor analysis. It works by comparing the frequency-domain phases of waveforms generated by two sources recorded at multiple stations. We first cross-correlate the records of the two sources at a single station. If the sources are co-located, this cross-correlation eliminates the phases of the Green's function. It leaves the relative phases of the source time functions, which should be the same across all stations so long as the spatial extent of the sources are small compared with the seismic wavelength. We therefore search for cross-correlation phases that are consistent across stations as an indication of co-located sources. We also introduce a method to obtain relative locations between the two sources, based on back-projection of interstation phase coherence. We apply this technique to analyse two tremor-like signals that are thought to be composed of a number of earthquakes. First, we analyse a 20 s long seismic precursor to a M 3.9 earthquake in central Alaska. The analysis locates the precursor to within 2 km of the mainshock, and it identifies several bursts of energy—potentially foreshocks or groups of foreshocks—within the precursor. Second, we examine several minutes of volcanic tremor prior to an eruption at Redoubt Volcano. We confirm that the tremor source is located close to repeating earthquakes identified earlier in the tremor sequence. The amplitude of the tremor diminishes about 30 s before the eruption, but the phase coherence results suggest that the tremor may persist at some level through this final interval.

Genetic Resources for Maize Cell Wall Biology1[C][W][OA

PubMed Central

Penning, Bryan W.; Hunter, Charles T.; Tayengwa, Reuben; Eveland, Andrea L.; Dugard, Christopher K.; Olek, Anna T.; Vermerris, Wilfred; Koch, Karen E.; McCarty, Donald R.; Davis, Mark F.; Thomas, Steven R.; McCann, Maureen C.; Carpita, Nicholas C.

2009-01-01

Grass species represent a major source of food, feed, and fiber crops and potential feedstocks for biofuel production. Most of the biomass is contributed by cell walls that are distinct in composition from all other flowering plants. Identifying cell wall-related genes and their functions underpins a fundamental understanding of growth and development in these species. Toward this goal, we are building a knowledge base of the maize (Zea mays) genes involved in cell wall biology, their expression profiles, and the phenotypic consequences of mutation. Over 750 maize genes were annotated and assembled into gene families predicted to function in cell wall biogenesis. Comparative genomics of maize, rice (Oryza sativa), and Arabidopsis (Arabidopsis thaliana) sequences reveal differences in gene family structure between grass species and a reference eudicot species. Analysis of transcript profile data for cell wall genes in developing maize ovaries revealed that expression within families differed by up to 100-fold. When transcriptional analyses of developing ovaries before pollination from Arabidopsis, rice, and maize were contrasted, distinct sets of cell wall genes were expressed in grasses. These differences in gene family structure and expression between Arabidopsis and the grasses underscore the requirement for a grass-specific genetic model for functional analyses. A UniformMu population proved to be an important resource in both forward- and reverse-genetics approaches to identify hundreds of mutants in cell wall genes. A forward screen of field-grown lines by near-infrared spectroscopic screen of mature leaves yielded several dozen lines with heritable spectroscopic phenotypes. Pyrolysis-molecular beam mass spectrometry confirmed that several nir mutants had altered carbohydrate-lignin compositions. PMID:19926802

Cognitive performance in children with acute early-onset anorexia nervosa.

PubMed

van Noort, Betteke Maria; Pfeiffer, Ernst; Ehrlich, Stefan; Lehmkuhl, Ulrike; Kappel, Viola

2016-11-01

When anorexia nervosa (AN) occurs in children below the age of 14 years, it is referred to as early-onset AN (EO-AN). Over the last years, there has been an increased focus on the role of cognitive functioning in the development and maintenance of AN. Adults with AN show inefficiencies in cognitive functions such as flexibility and central coherence. Systematic neuropsychological examinations of patients with EO-AN are missing. Thirty children with EO-AN and 30 adolescents with AN, as well as 60 healthy controls (HC) underwent an extensive neuropsychological examination. ANOVAs with post hoc tests and explorative regression analyses were conducted. Patients with EO-AN (mean age = 2.17 ± 1.57 years) showed no significant differences in flexibility, inhibition, planning, central coherence, visuospatial short- and long-term memory or recognition in comparison to HC (mean age = 11.62 ± 1.29 years). Performance of adolescents with AN (mean age = 15.93 ± 0.70 years) was not significantly different compared to HC (mean age = 16.20 ± 1.26 years). Explorative regression analyses revealed a significant interaction of age and group for flexibility (adjusted R 2  = 0.30, F = 17.85, p = 0.013, η p 2  = 0.32). Contrary to expectations, the current study could not confirm the presence of inefficient cognitive processing in children with EO-AN compared to HC. Nonetheless, the expected age-related improvement of flexibility might be disrupted in children and adolescents with AN. Longitudinal neuropsychological examinations are necessary to provide more information about the role of cognitive functioning in the development and maintenance of AN.

Identification of BRCA1 missense substitutions that confer partial functional activity: potential moderate risk variants?

PubMed

Lovelock, Paul K; Spurdle, Amanda B; Mok, Myth T S; Farrugia, Daniel J; Lakhani, Sunil R; Healey, Sue; Arnold, Stephen; Buchanan, Daniel; Couch, Fergus J; Henderson, Beric R; Goldgar, David E; Tavtigian, Sean V; Chenevix-Trench, Georgia; Brown, Melissa A

2007-01-01

Many of the DNA sequence variants identified in the breast cancer susceptibility gene BRCA1 remain unclassified in terms of their potential pathogenicity. Both multifactorial likelihood analysis and functional approaches have been proposed as a means to elucidate likely clinical significance of such variants, but analysis of the comparative value of these methods for classifying all sequence variants has been limited. We have compared the results from multifactorial likelihood analysis with those from several functional analyses for the four BRCA1 sequence variants A1708E, G1738R, R1699Q, and A1708V. Our results show that multifactorial likelihood analysis, which incorporates sequence conservation, co-inheritance, segregation, and tumour immunohistochemical analysis, may improve classification of variants. For A1708E, previously shown to be functionally compromised, analysis of oestrogen receptor, cytokeratin 5/6, and cytokeratin 14 tumour expression data significantly strengthened the prediction of pathogenicity, giving a posterior probability of pathogenicity of 99%. For G1738R, shown to be functionally defective in this study, immunohistochemistry analysis confirmed previous findings of inconsistent 'BRCA1-like' phenotypes for the two tumours studied, and the posterior probability for this variant was 96%. The posterior probabilities of R1699Q and A1708V were 54% and 69%, respectively, only moderately suggestive of increased risk. Interestingly, results from functional analyses suggest that both of these variants have only partial functional activity. R1699Q was defective in foci formation in response to DNA damage and displayed intermediate transcriptional transactivation activity but showed no evidence for centrosome amplification. In contrast, A1708V displayed an intermediate transcriptional transactivation activity and a normal foci formation response in response to DNA damage but induced centrosome amplification. These data highlight the need for a range of functional studies to be performed in order to identify variants with partially compromised function. The results also raise the possibility that A1708V and R1699Q may be associated with a low or moderate risk of cancer. While data pooling strategies may provide more information for multifactorial analysis to improve the interpretation of the clinical significance of these variants, it is likely that the development of current multifactorial likelihood approaches and the consideration of alternative statistical approaches will be needed to determine whether these individually rare variants do confer a low or moderate risk of breast cancer.

Thyroid function and neuropsychological status in older adults.

PubMed

Shrestha, Srishti; Bloom, Michael S; Yucel, Recai; Seegal, Richard F; Rej, Robert; McCaffrey, Robert J; Fitzgerald, Edward F

2016-10-01

Overt thyroid dysfunction is recognized as a risk factor for neuropsychological deficits in aging populations, yet evidence for how changes in levels of circulatory thyroid hormones impact specific neuropsychological domains is limited. Here we report cross-sectional associations between serum thyroid hormone concentrations and several neuropsychological function domains among men and women aged 55-74years. We administered neuropsychological tests to assess memory, learning, executive function, measures of attention, visuospatial function, affective state, and motor function. Multivariable linear regression analyses were performed adjusting for age, sex, education, and cigarette smoking. Effects were reported as differences in test scores per one interquartile range (IQR) increase in hormone concentration. Higher total thyroxine (T4) and free thyroxine (fT4) were associated with improved visuospatial function, as measured by Block Design Subtest total scores; associated increments per IQR differences in T4 and fT4 were 15% and 19%, respectively (false discovery rate q-values <0.05). We also detected statistical interactions between age and fT4 for effects in tasks of memory and learning. Concurrent increases in age and fT4 were associated with deficits in memory and learning as measured by California Verbal Learning Test subtests (10% and 16% deficits in t-score and short delay free recall score, respectively). Our findings suggest that changes in thyroid hormones may have important implications for neuropsychological function in aging populations. Further large-scale studies with comprehensive thyroid function and neuropsychological outcome assessments are warranted to confirm these results. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis of plutonium trifluoride by hydro-fluorination and novel thermodynamic data for the PuF3-LiF system

NASA Astrophysics Data System (ADS)

Tosolin, A.; Souček, P.; Beneš, O.; Vigier, J.-F.; Luzzi, L.; Konings, R. J. M.

2018-05-01

PuF3 was synthetized by hydro-fluorination of PuO2 and subsequent reduction of the product by hydrogenation. The obtained PuF3 was analysed by X-Ray Diffraction (XRD) and found phase-pure. High purity was also confirmed by the melting point analysis using Differential Scanning Calorimetry (DSC). PuF3 was then used for thermodynamic assessment of the PuF3-LiF system. Phase equilibrium points and enthalpy of fusion of the eutectic composition were measured by DSC. XRD analyses of selected samples after DSC measurement confirm that after solidification from the liquid, the system returns to a mixture of LiF and PuF3.

Characterization of Paecilomyces variotii and Talaromyces amestolkiae in Korea Based on the Morphological Characteristics and Multigene Phylogenetic Analyses

PubMed Central

Nguyen, Thi Thuong Thuong; Paul, Narayan Chandra

2016-01-01

During fungal diversity surveys of the order Eurotiales in Korea, two fungal strains, EML-DG33-1 and EML-NCP50, were isolated from samples of rat dung and fig tree leaf collected at a garden located in Gwangju in 2014. To complete the National Species List of Korea, it is a prerequisite to verify whether many questionable species, which were previously recorded but not confirmed, indeed present in Korea. Herein, the isolates were confirmed as undescribed species, Paecilomyces variotii and Talaromyces amestolkiae based on the combination of morphological and phylogenetic analyses of multigenes including the rDNA internal transcribed spacer, β-tubulin, and RNA polymerase II subunit 2. PMID:28154482

Confirmation of the Basic Psychological Needs in Exercise Scale (BPNES) With a Sample of People who do Healthy Exercise

PubMed Central

Moreno-Murcia, Juan A; Martínez-Galindo, Celestina; Moreno-Pérez, Víctor; Marcos, Pablo J.; Borges, Fernanda

2012-01-01

This study aimed to cross-validate the psychometric properties of the Basic Psychological Needs in Exercise Scale (BPNES) by Vlachopoulos and Michailidou, 2006 in a Spanish context. Two studies were conducted. Confirmatory factor analysis results confirmed the hypothesized three-factor solution In addition, we documented evidence of reliability, analysed as internal consistency and temporal stability. Future studies should analyse the scale's validity and reliability with different populations and check their experimental effect. Key pointsThe Basic Psychological Needs in Exercise Scale (BPNES) is valid and reliable for measuring basic psychological needs in healthy physical exercise in the Spanish context.The factor structure of three correlated factors has shown minimal invariance across gender. PMID:24149130

Biochemical characterization of the selenoproteome in Gallus gallus via bioinformatics analysis: structure-function relationships and interactions of binding molecules.

PubMed

Zhu, Shi-Yong; Li, Xue-Nan; Sun, Xiao-Chen; Lin, Jia; Li, Wei; Zhang, Cong; Li, Jin-Long

2017-02-22

Knowledge about mammalian selenoproteins is increasing. However, the selenoproteome of birds remains considerably less understood, especially concerning its biochemical characterization, structure-function relationships and the interactions of binding molecules. In this work, the SECIS elements, subcellular localization, protein domains and interactions of binding molecules of the selenoproteome in Gallus gallus were analyzed using bioinformatics tools. We carried out comprehensive analyses of the structure-function relationships and interactions of the binding molecules of selenoproteins, to provide biochemical characterization of the selenoproteome in Gallus gallus. Our data provided a wealth of information on the biochemical functions of bird selenoproteins. Members of the selenoproteome were found to be involved in various biological processes in chickens, such as in antioxidants, maintenance of the redox balance, Se transport, and interactions with metals. Six membrane-bound selenoproteins (SelI, SelK, SelS, SelT, DIO1 and DIO3) played important roles in maintaining the membrane integrity. Chicken selenoproteins were classified according to their ligand binding sites as zinc-containing matrix metalloselenoproteins (Sep15, MsrB1, SelW and SelM), POP-containing selenoproteins (GPx1-4), FAD-interacting selenoproteins (TrxR1-3), secretory transport selenoproteins (GPx3 and SelPa) and other selenoproteins. The results of our study provided new evidence for the unknown biological functions of the selenoproteome in birds. Future research is required to confirm the novel biochemical functions of bird selenoproteins.

Isolation and Functional Analyses of a Putative Floral Homeotic C-Function Gene in a Basal Eudicot London Plane Tree (Platanus acerifolia)

PubMed Central

Liu, Guofeng; Bao, Manzhu

2013-01-01

The identification of mutants in model plant species has led to the isolation of the floral homeotic function genes that play crucial roles in flower organ specification. However, floral homeotic C-function genes are rarely studied in basal eudicots. Here, we report the isolation and characterization of the AGAMOUS (AG) orthologous gene (PaAG) from a basal eudicot London plane tree (Platanus acerifolia Willd). Phylogenetic analysis showed that PaAG belongs to the C- clade AG group of genes. PaAG was found to be expressed predominantly in the later developmental stages of male and female inflorescences. Ectopic expression of PaAG-1 in tobacco (Nicotiana tabacum) resulted in morphological alterations of the outer two flower whorls, as well as some defects in vegetative growth. Scanning electron micrographs (SEMs) confirmed homeotic sepal-to-carpel transformation in the transgenic plants. Protein interaction assays in yeast cells indicated that PaAG could interact directly with PaAP3 (a B-class MADS-box protein in P. acerifolia), and also PaSEP1 and PaSEP3 (E-class MADS-box proteins in P. acerifolia). This study performed the functional analysis of AG orthologous genes outside core eudicots and monocots. Our findings demonstrate a conserved functional role of AG homolog in London plane tree, which also represent a contribution towards understanding the molecular mechanisms of flower development in this monoecious tree species. PMID:23691041

Immunological biomarkers in salt miners exposed to salt dust, diesel exhaust and nitrogen oxides.

PubMed

Backé, Eva; Lotz, Gabriele; Tittelbach, Ulrike; Plitzko, Sabine; Gierke, Erhardt; Schneider, Wolfram Dietmar

2004-06-01

Air pollutants can affect lung function and also the immune system. In a study about lung function of salt miners in relation to the complex exposure in a salt mine, we also analysed selected immunological parameters and inflammation markers in the blood of miners. Effect of salt dust, diesel exhaust, nitrogen oxides (NOx) and smoking on the biomarkers was analysed. Blood was drawn from 286 salt miners, and the soluble intercellular adhesion molecule-1 (s-ICAM), monocyte chemotactic protein (MCP-1) and clara cell protein (CC16) were analysed by an immunoassay, blood profile was done and lymphocyte subpopulations (CD3, CD3/CD4, CD3/CD8, CD19, NK-cells, CD3/HLA-DR) were determined by flow cytometry. Salt dust was measured by two-step gravimetry (personal sampling). Diesel exhaust was measured as elemental carbon concentration by coulometry. NOx were determined by an electrochemical cell method. Differences between non-smokers, former smokers and active smokers were analysed by analysis of variance. Linear regression analysis to describe exposure-response relationships was done with regard to confounding factors [smoking, inflammatory diseases, time of blood drawing, respiratory infection and body-mass index (BMI)]. Significant differences between non-smokers and active smokers were found for most of the leukocyte types (e.g. granulocytes P = 0.000, lymphocytes P = 0.002, T-cells P = 0.033) and for some soluble parameters (ICAM P = 0.000, IgM P = 0.007, IgE P = 0.035). Increasing numbers of total lymphocytes, T-cells and HLA-DR positive T-cells in relation to exposure were found by linear regression analysis (e.g. for inhalable dust:total lymphocytes P = 0.011, T-cells P = 0.061, HLA-DR positive T-cells P = 0.007). CONCLUSION. Comparison of immunological markers in non-smokers and active smokers confirms leukocytosis and inflammation following tobacco consumption. The combined exposure of salt dust, diesel exhaust and NOx seems to influence the immune system. Together, the results suggest that the analysis of leukocytes and their subsets can complete other investigations (lung function, questionnaire) to monitor exposure-response relationships in occupational studies investigating the effect of inhaled substances. Longitudinal studies will be necessary to determine the predictive value of the immunological changes. Copyright 2004 Springer-Verlag

Identification of a Novel Deletion in AVP-NPII Gene in a Patient with Central Diabetes Insipidus.

PubMed

Deniz, Ferhat; Acar, Ceren; Saglar, Emel; Erdem, Beril; Karaduman, Tugce; Yonem, Arif; Cagiltay, Eylem; Ay, Seyit Ahmet; Mergen, Hatice

2015-01-01

Central Diabetes Insipidus (CDI) is caused by a deficiency of antidiuretic hormone and characterized by polyuria, polydipsia and inability to concentrate urine. Our objective was to present the results of the molecular analyses of AVP-neurophysin II (AVP-NPII) gene in a large familial neurohypophyseal (central) DI pedigree. A male patient and his family members were analyzed and the prospective clinical data were collected. The proband applied to hospital for eligibility to be a recruit in Armed Forces. The patient had severe polyuria (20 L/day), polydipsia (20.5 L/day), fatique, and deep thirstiness. CDI was confirmed with the water deprivation-desmopressin test according to an increase in urine osmolality from 162 mOsm/kg to 432 mOsm/kg after desmopressin acetate injection. To evaluate the coding regions of AVP-NPII gene, polymerase chain reactions were performed and amplified regions were submitted to direct sequence analysis. We detected a heterozygous three base pair deletion at codon 69-70 (207_209delGGC) in exon 2, which lead to a deletion of the amino acid alanine. A three-dimensional protein structure prediction was shown for the deleted AVP-NPII and compared with the wild type. The three base pair deletion may yield an abnormal AVP precursor in neurophysin moiety, but further functional analyses are needed to understand the function of the deleted protein. © 2015 by the Association of Clinical Scientists, Inc.

A systematic study on drug-response associated genes using baseline gene expressions of the Cancer Cell Line Encyclopedia

NASA Astrophysics Data System (ADS)

Liu, Xiaoming; Yang, Jiasheng; Zhang, Yi; Fang, Yun; Wang, Fayou; Wang, Jun; Zheng, Xiaoqi; Yang, Jialiang

2016-03-01

We have studied drug-response associated (DRA) gene expressions by applying a systems biology framework to the Cancer Cell Line Encyclopedia data. More than 4,000 genes are inferred to be DRA for at least one drug, while the number of DRA genes for each drug varies dramatically from almost 0 to 1,226. Functional enrichment analysis shows that the DRA genes are significantly enriched in genes associated with cell cycle and plasma membrane. Moreover, there might be two patterns of DRA genes between genders. There are significantly shared DRA genes between male and female for most drugs, while very little DRA genes tend to be shared between the two genders for a few drugs targeting sex-specific cancers (e.g., PD-0332991 for breast cancer and ovarian cancer). Our analyses also show substantial difference for DRA genes between young and old samples, suggesting the necessity of considering the age effects for personalized medicine in cancers. Lastly, differential module and key driver analyses confirm cell cycle related modules as top differential ones for drug sensitivity. The analyses also reveal the role of TSPO, TP53, and many other immune or cell cycle related genes as important key drivers for DRA network modules. These key drivers provide new drug targets to improve the sensitivity of cancer therapy.

Integrating Metagenomics and NanoSIMS to Investigate the Evolution and Ecophysiology of Magnetotactic Bacteria

NASA Astrophysics Data System (ADS)

Lin, W.; Zhang, W.; He, M.; Pan, Y.

2017-12-01

Magnetotactic bacteria (MTB) synthesize intracellular nano-sized magnetite (Fe3O4) and/or greigite (Fe3S4) crystals, called magnetosomes, which impart a permanent magnetic dipole moment to the cell causing it to align along the geomagnetic field lines as it swims. MTB play essential roles in global cycling of Fe, S, N and C, and represent an excellent model system not just for the investigation of the mechanisms of microbial engines that drive Earth's biogeochemical cycles but also for magnetotaxis and microbial biomineralization. Most of the previous studies on MTB were based on 16S rRNA gene-targeting analyses, which are powerful approaches to characterize the diversity, ecology and biogeography of MTB in nature. However, these approaches are somewhat limited in the physiological detail they can provide. In the present study, we have combined the genome-resolved metagenomics and nanoscale secondary ion mass spectrometry (NanoSIMS) analyses to study the genomic information, biomineralization mechanism and metabolic potential of environmental MTB. Two nearly complete genomes from uncultivated MTB belonging to the Nitrospirae phylum were reconstructed and their proposed metabolisms were further investigated and confirmed through NanoSIMS analyses. These results improve our understanding about the ecophysiology and evolution of MTB and their environmental function. The development of metagenomics-NanoSIMS integrated approach will provide a powerful tool for the research of geomicrobiology and environmental microbiology.

The influence of psychiatric screening in healthy populations selection: a new study and meta-analysis of functional 5-HTTLPR and rs25531 polymorphisms and anxiety-related personality traits.

PubMed

Minelli, Alessandra; Bonvicini, Cristian; Scassellati, Catia; Sartori, Riccardo; Gennarelli, Massimo

2011-03-31

A genetic liability for anxiety-related personality traits in healthy subjects has been associated with the functional serotonin transporter promoter polymorphism (5-HTTLPR), although the data are somewhat conflicting. Moreover, only one study has investigated the functional significance of the 5-HTTLPR/rs25531 haplotypes in relation to anxiety traits in healthy subjects. We tested whether the 5-HTTLPR polymorphism and the 5-HTTLPR/rs25531 haplotypes are linked to Harm Avoidance (HA) using an association study (STUDY I) and a meta-analytic approach (STUDY II). STUDY I: A total of 287 unrelated Italian volunteers were screened for DSM-IV Axis I disorders and genotyped for the 5-HTTLPR and rs25531 (A/G) polymorphisms. Different functional haplotype combinations were also analyzed. STUDY II: A total of 44 studies were chosen for a meta-analysis of the putative association between 5-HTTLPR and anxiety-related personality traits. STUDY I: In the whole sample of 287 volunteers, we found that the SS genotype and S'S' haplotypes were associated with higher scores on HA. However, because the screening assessed by Mini-International Neuropsychiatric Interview (M.I.N.I.) showed the presence of 55 volunteers affected by depression or anxiety disorders, we analyzed the two groups ("disordered" and "healthy") separately. The data obtained did indeed confirm that in the "healthy" group, the significant effects of the SS genotype and S'S' haplotypes were lost, but they remained in the "disordered" group. STUDY II: The results of the 5-HTTLPR meta-analysis with anxiety-related traits in the whole sample confirmed the association of the SS genotype with higher anxiety-related traits scores in Caucasoids; however, when we analyzed only those studies that used structured psychiatric screening, no association was found. This study demonstrates the relevance to perform analyses on personality traits only in DSM-IV axis I disorder-free subjects. Furthermore, we did not find an association between functional serotonin transporter gene polymorphisms and anxiety traits in healthy subjects screened through a structured psychiatric interview.

Descriptive epidemiology of typhoid fever during an epidemic in Harare, Zimbabwe, 2012.

PubMed

Polonsky, Jonathan A; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J

2014-01-01

Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range.

Descriptive Epidemiology of Typhoid Fever during an Epidemic in Harare, Zimbabwe, 2012

PubMed Central

Polonsky, Jonathan A.; Martínez-Pino, Isabel; Nackers, Fabienne; Chonzi, Prosper; Manangazira, Portia; Van Herp, Michel; Maes, Peter; Porten, Klaudia; Luquero, Francisco J.

2014-01-01

Background Typhoid fever remains a significant public health problem in developing countries. In October 2011, a typhoid fever epidemic was declared in Harare, Zimbabwe - the fourth enteric infection epidemic since 2008. To orient control activities, we described the epidemiology and spatiotemporal clustering of the epidemic in Dzivaresekwa and Kuwadzana, the two most affected suburbs of Harare. Methods A typhoid fever case-patient register was analysed to describe the epidemic. To explore clustering, we constructed a dataset comprising GPS coordinates of case-patient residences and randomly sampled residential locations (spatial controls). The scale and significance of clustering was explored with Ripley K functions. Cluster locations were determined by a random labelling technique and confirmed using Kulldorff's spatial scan statistic. Principal Findings We analysed data from 2570 confirmed and suspected case-patients, and found significant spatiotemporal clustering of typhoid fever in two non-overlapping areas, which appeared to be linked to environmental sources. Peak relative risk was more than six times greater than in areas lying outside the cluster ranges. Clusters were identified in similar geographical ranges by both random labelling and Kulldorff's spatial scan statistic. The spatial scale at which typhoid fever clustered was highly localised, with significant clustering at distances up to 4.5 km and peak levels at approximately 3.5 km. The epicentre of infection transmission shifted from one cluster to the other during the course of the epidemic. Conclusions This study demonstrated highly localised clustering of typhoid fever during an epidemic in an urban African setting, and highlights the importance of spatiotemporal analysis for making timely decisions about targetting prevention and control activities and reinforcing treatment during epidemics. This approach should be integrated into existing surveillance systems to facilitate early detection of epidemics and identify their spatial range. PMID:25486292

Cellular organization and spectral diversity of GFP-like proteins in live coral cells studied by single and multiphoton imaging and microspectroscopy

NASA Astrophysics Data System (ADS)

Salih, Anya; Cox, Guy C.; Larkum, Anthony W.

2003-07-01

Tissues of many marine invertebrates of class Anthozoa contain intensely fluorescent or brightly coloured pigments. These pigments belong to a family of photoactive proteins closely related to Green Fluorescent Protein (GFP), and their emissions range from blue to red wavelengths. The great diversity of these pigments has only recently been realised. To investigate the role of these proteins in corals, we have performed an in vivo fluorescent pigment (FP) spectral and cellular distribution analyses in live coral cells using single and multi-photon laser scanning imaging and microspectroscopy. These analyses revealed that even single colour corals contain spectroscopically heterogeneous pigment mixtures, with 2-5 major colour types in the same area of tissue. They were typically arranged in step-wise light emission energy gradients (e.g. blue, green, yellow, red). The successive overlapping emission-excitation spectral profiles of differently coloured FPs suggested that they were suited for sequential energy coupling. Traces of red FPs (emission = 570-660 nm) were present, even in non-red corals. We confirmed that radiative energy transfer could occur between separate granules of blue and green FPs and that energy transfer was inversely proportional to the square of the distance between them. Multi-photon micro-spectrofluorometric analysis gave significantly improved spectral resolution by restricting FP excitation to a single point in the focal plane of the sample. Pigment heterogeneity at small scales within granules suggested that fluorescence resonance energy transfer (FRET) might be occurring, and we confirmed that this was the case. Thus, energy transfer can take place both radiatively and by FRET, probably functioning in photoprotection by dissipation of excessive solar radiation.

Mass spectrometric identification of proteins that interact through specific domains of the poly(A) binding protein

PubMed Central

Zhang, Chongxu; Nielsen, Maria E. O.; Chiang, Yueh-Chin; Kierkegaard, Morten; Wang, Xin; Lee, Darren J.; Andersen, Jens S.; Yao, Gang

2013-01-01

Poly(A) binding protein (PAB1) is involved in a number of RNA metabolic functions in eukaryotic cells and correspondingly is suggested to associate with a number of proteins. We have used mass spectrometric analysis to identify 55 non-ribosomal proteins that specifically interact with PAB1 from Saccharomyces cerevisiae. Because many of these factors may associate only indirectly with PAB1 by being components of the PAB1-mRNP structure, we additionally conducted mass spectrometric analyses on seven metabolically defined PAB1 deletion derivatives to delimit the interactions between these proteins and PAB1. These latter analyses identified 13 proteins whose associations with PAB1 were reduced by deleting one or another of PAB1’s defined domains. Included in this list of 13 proteins were the translation initiation factors eIF4G1 and eIF4G2, translation termination factor eRF3, and PBP2, all of whose previously known direct interactions with specific PAB1 domains were either confirmed, delimited, or extended. The remaining nine proteins that interacted through a specific PAB1 domain were CBF5, SLF1, UPF1, CBC1, SSD1, NOP77, yGR250c, NAB6, and GBP2. In further study, UPF1, involved in nonsense-mediated decay, was confirmed to interact with PAB1 through the RRM1 domain. We additionally established that while the RRM1 domain of PAB1 was required for UPF1-induced acceleration of deadenylation during nonsense-mediated decay, it was not required for the more critical step of acceleration of mRNA decapping. These results begin to identify the proteins most likely to interact with PAB1 and the domains of PAB1 through which these contacts are made. PMID:22836166

Mass spectrometric identification of proteins that interact through specific domains of the poly(A) binding protein.

PubMed

Richardson, Roy; Denis, Clyde L; Zhang, Chongxu; Nielsen, Maria E O; Chiang, Yueh-Chin; Kierkegaard, Morten; Wang, Xin; Lee, Darren J; Andersen, Jens S; Yao, Gang

2012-09-01

Poly(A) binding protein (PAB1) is involved in a number of RNA metabolic functions in eukaryotic cells and correspondingly is suggested to associate with a number of proteins. We have used mass spectrometric analysis to identify 55 non-ribosomal proteins that specifically interact with PAB1 from Saccharomyces cerevisiae. Because many of these factors may associate only indirectly with PAB1 by being components of the PAB1-mRNP structure, we additionally conducted mass spectrometric analyses on seven metabolically defined PAB1 deletion derivatives to delimit the interactions between these proteins and PAB1. These latter analyses identified 13 proteins whose associations with PAB1 were reduced by deleting one or another of PAB1's defined domains. Included in this list of 13 proteins were the translation initiation factors eIF4G1 and eIF4G2, translation termination factor eRF3, and PBP2, all of whose previously known direct interactions with specific PAB1 domains were either confirmed, delimited, or extended. The remaining nine proteins that interacted through a specific PAB1 domain were CBF5, SLF1, UPF1, CBC1, SSD1, NOP77, yGR250c, NAB6, and GBP2. In further study, UPF1, involved in nonsense-mediated decay, was confirmed to interact with PAB1 through the RRM1 domain. We additionally established that while the RRM1 domain of PAB1 was required for UPF1-induced acceleration of deadenylation during nonsense-mediated decay, it was not required for the more critical step of acceleration of mRNA decapping. These results begin to identify the proteins most likely to interact with PAB1 and the domains of PAB1 through which these contacts are made.

A Comparative Study of Average, Linked Mastoid, and REST References for ERP Components Acquired during fMRI

PubMed Central

Yang, Ping; Fan, Chenggui; Wang, Min; Li, Ling

2017-01-01

In simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) studies, average reference (AR), and digitally linked mastoid (LM) are popular re-referencing techniques in event-related potential (ERP) analyses. However, they may introduce their own physiological signals and alter the EEG/ERP outcome. A reference electrode standardization technique (REST) that calculated a reference point at infinity was proposed to solve this problem. To confirm the advantage of REST in ERP analyses of synchronous EEG-fMRI studies, we compared the reference effect of AR, LM, and REST on task-related ERP results of a working memory task during an fMRI scan. As we hypothesized, we found that the adopted reference did not change the topography map of ERP components (N1 and P300 in the present study), but it did alter the task-related effect on ERP components. LM decreased or eliminated the visual working memory (VWM) load effect on P300, and the AR distorted the distribution of VWM location-related effect at left posterior electrodes as shown in the statistical parametric scalp mapping (SPSM) of N1. ERP cortical source estimates, which are independent of the EEG reference choice, were used as the golden standard to infer the relative utility of different references on the ERP task-related effect. By comparison, REST reference provided a more integrated and reasonable result. These results were further confirmed by the results of fMRI activations and a corresponding EEG-only study. Thus, we recommend the REST, especially with a realistic head model, as the optimal reference method for ERP data analysis in simultaneous EEG-fMRI studies. PMID:28529472

Toxicity evaluations of nanoclays and thermally degraded byproducts through spectroscopical and microscopical approaches

PubMed Central

Wagner, Alixandra; Eldawud, Reem; White, Andrew; Agarwal, Sushant; Stueckle, Todd A.; Sierros, Konstantinos A.; Rojanasakul, Yon; Gupta, Rakesh K.; Dinu, Cerasela Zoica

2016-01-01

Background Montmorillonite is a type of nanoclay that originates from the clay fraction of the soil and is incorporated into polymers to form nanocomposites with enhanced mechanical strength, barrier, and flammability properties used for food packaging, automotive, and medical devices. However, with implementation in such consumer applications, the interaction of montmorillonite-based composites or derived byproducts with biological systems needs to be investigated. Methods Herein we examined the potential of Cloisite Na+ (pristine) and Cloisite 30B (organically modified montmorillonite nanoclay) and their thermally degraded byproducts’ to induce toxicity in model human lung epithelial cells. The experimental set-up mimicked biological exposure in manufacturing and disposal areas and employed cellular treatments with occupationally relevant doses of nanoclays previously characterized using spectroscopical and microscopical approaches. For nanoclay-cellular interactions and for cellular analyses respectively, biosensorial-based analytical platforms were used, with induced cellular changes being confirmed via live cell counts, viability assays, and cell imaging. Results Our analysis of byproducts’ chemical and physical properties revealed both structural and functional changes. Real-time high throughput analyses of exposed cellular systems confirmed that nanoclay induced significant toxic effects, with Cloisite 30B showing time-dependent decreases in live cell count and cellular viability relative to control and pristine nanoclay, respectively. Byproducts produced less toxic effects; all treatments caused alterations in the cell morphology upon exposure. Conclusions Our morphological, behavioral, and viability cellular changes show that nanoclays have the potential to produce toxic effects when used both in manufacturing or disposal environments. General significance The reported toxicological mechanisms prove the extensibility of a biosensorial-based platform for cellular behavior analysis upon treatment with a variety of nanomaterials. PMID:27612663

Efficacy and tolerability of Ginkgo biloba extract EGb 761® in dementia: a systematic review and meta-analysis of randomized placebo-controlled trials

PubMed Central

Gauthier, Serge; Schlaefke, Sandra

2014-01-01

The objective of this systematic review was to evaluate current evidence for the efficacy of Ginkgo biloba extract EGb 761® in dementia. Seven of 15 randomized, placebocontrolled trials in patients with dementia identified by database searches met all our selection criteria and were included in the meta-analysis. In these trials, patients were treated with 120 mg or 240 mg per day of the defined extract EGb 761 or placebo. Efficacy was assessed using validated tests and rating scales for the cognitive domain, the functional domain (activities of daily living), and global assessment. Tolerability was evaluated by risk differences based on incidences of adverse events and premature discontinuation rates. Of 2,684 outpatients randomized to receive treatment for 22–26 weeks, 2,625 represented the full analysis sets (1,396 for EGb 761 and 1,229 for placebo). Standardized mean differences for change in cognition (−0.52; 95% confidence interval [CI] −0.98, −0.05; P=0.03), activities of daily living (−0.44; 95% CI −0.68, −0.19; P<0.001), and global rating (−0.52; 95% CI −0.92, −0.12; P=0.01) significantly favored EGb 761 compared with placebo. Statistically significant superiority of EGb 761 over placebo was confirmed by responder analyses as well as for patients suffering from dementia with neuropsychiatric symptoms. Treatment-associated risks in terms of relative risks of adverse events and premature withdrawal rates did not differ noticeably between the two treatment groups. In conclusion, meta-analyses confirmed the efficacy and good tolerability of Ginkgo biloba extract EGb 761 in patients with dementia. PMID:25506211

In Vivo Evaluation and Imaging of a Bilayered Self-Assembled Skin Substitute Using a Decellularized Dermal Matrix Grafted on Mice.

PubMed

Beaudoin Cloutier, Chanel; Goyer, Benjamin; Perron, Cindy; Guignard, Rina; Larouche, Danielle; Moulin, Véronique J; Germain, Lucie; Gauvin, Robert; Auger, François A

2017-04-01

As time to final coverage is the essence for better survival outcome in severely burned patients, we have continuously strived to reduce the duration for the preparation of our bilayered self-assembled skin substitutes (SASS). These SASS produced in vitro by the self-assembly approach have a structure and functionality very similar to native skin. Recently, we have shown that a decellularized dermal matrix preproduced by the self-assembly approach could be used as a template to further obtain self-assembled skin substitute using a decellularized dermal template (SASS-DM) in vitro. Thus, the production period with patient cells was then reduced to about 1 month. Herein, preclinical animal experiments have been performed to confirm the integration and evolution of such a graft and compare the maturation of SASS and SASS-DM in vivo. Both tissues, reconstructed from adult or newborn cells, were grafted on athymic mice. Green fluorescent protein-transfected keratinocytes were also used to follow grafted tissues weekly for 6 weeks using an in vivo imaging system (IVIS). Cell architecture and differentiation were studied with histological and immunofluorescence analyses at each time point. Graft integration, macroscopic evolution, histological analyses, and expression of skin differentiation markers were similar between both skin substitutes reconstructed from either newborn or adult cells, and IVIS observations confirmed the efficient engraftment of SASS-DM. In conclusion, our in vivo graft experiments on a mouse model demonstrated that the SASS-DM had equivalent macroscopic, histological, and differentiation evolution over a 6-week period, when compared with the SASS. The tissue-engineered SASS-DM could improve clinical availability and advantageously shorten the time necessary for the definitive wound coverage of severely burned patients.

A Comparative Study of Average, Linked Mastoid, and REST References for ERP Components Acquired during fMRI.

PubMed

Yang, Ping; Fan, Chenggui; Wang, Min; Li, Ling

2017-01-01

In simultaneous electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) studies, average reference (AR), and digitally linked mastoid (LM) are popular re-referencing techniques in event-related potential (ERP) analyses. However, they may introduce their own physiological signals and alter the EEG/ERP outcome. A reference electrode standardization technique (REST) that calculated a reference point at infinity was proposed to solve this problem. To confirm the advantage of REST in ERP analyses of synchronous EEG-fMRI studies, we compared the reference effect of AR, LM, and REST on task-related ERP results of a working memory task during an fMRI scan. As we hypothesized, we found that the adopted reference did not change the topography map of ERP components (N1 and P300 in the present study), but it did alter the task-related effect on ERP components. LM decreased or eliminated the visual working memory (VWM) load effect on P300, and the AR distorted the distribution of VWM location-related effect at left posterior electrodes as shown in the statistical parametric scalp mapping (SPSM) of N1. ERP cortical source estimates, which are independent of the EEG reference choice, were used as the golden standard to infer the relative utility of different references on the ERP task-related effect. By comparison, REST reference provided a more integrated and reasonable result. These results were further confirmed by the results of fMRI activations and a corresponding EEG-only study. Thus, we recommend the REST, especially with a realistic head model, as the optimal reference method for ERP data analysis in simultaneous EEG-fMRI studies.

A novel NOTCH3 mutation identified in patients with oral cancer by whole exome sequencing.

PubMed

Yi, Yanjun; Tian, Zhuowei; Ju, Houyu; Ren, Guoxin; Hu, Jingzhou

2017-06-01

Oral cancer is a serious disease caused by environmental factors and/or susceptible genes. In the present study, in order to identify useful genetic biomarkers for cancer prediction and prevention, and for personalized treatment, we detected somatic mutations in 5 pairs of oral cancer tissues and blood samples using whole exome sequencing (WES). Finally, we confirmed a novel nonsense single-nucleotide polymorphism (SNP; chr19:15288426A>C) in the NOTCH3 gene with sanger sequencing, which resulted in a N1438T mutation in the protein sequence. Using multiple in silico analyses, this variant was found to mildly damaging effects on the NOTCH3 gene, which was supported by the results from analyses using PANTHER, SNAP and SNPs&GO. However, further analysis using Mutation Taster revealed that this SNP had a probability of 0.9997 to be 'disease causing'. In addition, we performed 3D structure simulation analysis and the results suggested that this variant had little effect on the solubility and hydrophobicity of the protein and thus on its function; however, it decreased the stability of the protein by increasing the total energy following minimization (-1,051.39 kcal/mol for the mutant and -1,229.84 kcal/mol for the native) and decreasing one stabilizing residue of the protein. Less stability of the N1438T mutant was also supported by analysis using I-Mutant with a DDG value of -1.67. Overall, the present study identified and confirmed a novel mutation in the NOTCH3 gene, which may decrease the stability of NOTCH3, and may thus prove to be helpful in cancer prognosis.

Murine recessive hereditary spherocytosis, sph/sph, is caused by a mutation in the erythroid alpha-spectrin gene.

PubMed

Wandersee, N J; Birkenmeier, C S; Gifford, E J; Mohandas, N; Barker, J E

2000-01-01

Spectrin, a heterodimer of alpha- and beta-subunits, is the major protein component of the red blood cell membrane skeleton. The mouse mutation, sph, causes an alpha-spectrin-deficient hereditary spherocytosis with the severe phenotype typical of recessive hereditary spherocytosis in humans. The sph mutation maps to the erythroid alpha-spectrin locus, Spna1, on Chromosome 1. Scanning electron microscopy, osmotic gradient ektacytometry, cDNA cloning, RT-PCR, nucleic acid sequencing, and Northern blot analyses were used to characterize the wild type and sph alleles of the Spna1 locus. Our results confirm the spherocytic nature of sph/sph red blood cells and document a mild spherocytic transition in the +/sph heterozygotes. Sequencing of the full length coding region of the Spna1 wild type allele from the C57BL/6J strain of mice reveals a 2414 residue deduced amino acid sequence that shows the typical 106-amino-acid repeat structure previously described for other members of the spectrin protein family. Sequence analysis of RT-PCR clones from sph/sph alpha-spectrin mRNA identified a single base deletion in repeat 5 that would cause a frame shift and premature termination of the protein. This deletion was confirmed in sph/sph genomic DNA. Northern blot analyses of the distribution of Spna1 mRNA in non-erythroid tissues detects the expression of 8, 2.5 and 2.0 kb transcripts in adult heart. These results predict the heart as an additional site where alpha-spectrin mutations may produce a phenotype and raise the possibility that a novel functional class of small alpha-spectrin isoforms may exist.

Evaluation of gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) for the quality assessment of citrus liqueurs.

PubMed

Schipilliti, Luisa; Bonaccorsi, Ivana; Cotroneo, Antonella; Dugo, Paola; Mondello, Luigi

2013-02-27

Citrus liqueurs are alcoholic beverages obtained by maceration. The European Parliament protects these alcoholic beverages, forbidding the addition of nature-identical flavoring substances. However, for economical and technological reasons, producers often add natural and/or synthetic flavors to the alcoholic syrup, obtaining artificial spirit drinks. The aim of this study is to investigate the authenticity of Italian liqueurs, of lemon, bergamot, and mandarin (locally known as "limoncello", "bargamino", and "mandarinetto"), comparing the carbon isotope ratios with values determined in genuine cold-pressed peel oils. Authenticity assessment was performed using headspace-solid phase microextraction coupled to gas chromatography-combustion-isotope ratio mass spectrometry. Additional analyses were performed by direct enantioselective gas chromatography to determine the enantiomeric distribution of selected chiral volatiles and by gas chromatography-mass spectrometry for the qualitative analyses of the samples. The method allowed confirmation of genuineness. Enantioselective gas chromatography analyses confirmed the results, demonstrating the reliability of the method.

Axons giving rise to the palisade endings of feline extraocular muscles display motor features.

PubMed

Zimmermann, Lars; Morado-Díaz, Camilo J; Davis-López de Carrizosa, María A; de la Cruz, Rosa R; May, Paul J; Streicher, Johannes; Pastor, Ángel M; Blumer, Roland

2013-02-13

Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function. Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection. We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements. This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings.

Axons Giving Rise to the Palisade Endings of Feline Extraocular Muscles Display Motor Features

PubMed Central

Zimmermann, Lars; Morado-Díaz, Camilo J.; de Carrizosa, María A. Davis-López; de la Cruz, Rosa R.; May, Paul J.; Streicher, Johannes; Pastor, Ángel M.; Blumer, Roland

2016-01-01

Palisade endings are nerve specializations found in the extraocular muscles (EOMs) of mammals, including primates. They have long been postulated to be proprioceptors. It was recently demonstrated that palisade endings are cholinergic and that in monkeys they originate from the EOM motor nuclei. Nevertheless, there is considerable difference of opinion concerning the nature of palisade ending function. Palisade endings in EOMs were examined in cats to test whether they display motor or sensory characteristics. We injected an anterograde tracer into the oculomotor or abducens nuclei and combined tracer visualization with immunohistochemistry and α-bungarotoxin staining. Employing immunohistochemistry, we performed molecular analyses of palisade endings and trigeminal ganglia to determine whether cat palisade endings are a cholinergic trigeminal projection. We confirmed that palisade endings are cholinergic and showed, for the first time, that they, like extraocular motoneurons, are also immunoreactive for calcitonin gene-related peptide. Following tracer injection into the EOM nuclei, we observed tracer-positive palisade endings that exhibited choline acetyl transferase immunoreactivity. The tracer-positive nerve fibers supplying palisade endings also established motor terminals along the muscle fibers, as demonstrated by α-bungarotoxin. Neither the trigeminal ganglion nor the ophthalmic branch of the trigeminal nerve contained cholinergic elements. This study confirms that palisade endings originate in the EOM motor nuclei and further indicates that they are extensions of the axons supplying the muscle fiber related to the palisade. The present work excludes the possibility that they receive cholinergic trigeminal projections. These findings call into doubt the proposed proprioceptive function of palisade endings. PMID:23407938

Molecular orbital studies (hardness, chemical potential, electronegativity and electrophilicity), vibrational spectroscopic investigation and normal coordinate analysis of 5-{1-hydroxy-2-[(propan-2-yl)amino]ethyl}benzene-1,3-diol

NASA Astrophysics Data System (ADS)

Muthu, S.; Renuga, S.

2014-01-01

FT-IR and FT-Raman spectra of 5-{1-hydroxy-2-[(propan-2-yl) amino] ethyl} benzene-1,3-diol (abbrevi- 54 ated as HPAEBD) were recorded in the region 4000-450 cm-1 and 4000-100 cm-1 respectively. The structure of the molecule was optimized and the structural characteristics were determined by density functional theory (B3LYP) and HF method with 6-31 G(d,p) as basis set. The theoretical wave numbers were scaled and compared with experimental FT-IR and FT-Raman spectra. A detailed interpretation of the vibrational spectra of this compound has been made on the basis of the calculated Potential energy distribution (PED). Stability of the molecule arising from hyperconjugation and charge delocalization is confirmed by the natural bond orbital analysis (NBO). The results show that electron density (ED) in the σ antibonding orbitals and E (2) energies confirm the occurrence of intra molecular charge transfer (ICT) within the molecule. The molecule orbital contributions were studied by using the total (TDOS), sum of α and β electron (αβDOS) density of States. Mulliken population analysis of atomic charges is also calculated. The calculated HOMO and LUMO energy gap shows that charge transfer occurs within the molecule. The electron density-based local reactivity descriptors such as Fukui functions were calculated to explain the chemical selectivity or reactivity site in this compound. On the basis of vibrational analyses, the thermodynamic properties of title compound at different temperatures have been calculated.

Biocompatible nanogel derived from functionalized dextrin for targeted delivery of doxorubicin hydrochloride to MG 63 cancer cells.

PubMed

Das, Dipankar; Rameshbabu, Arun Prabhu; Ghosh, Paulomi; Patra, Priyapratim; Dhara, Santanu; Pal, Sagar

2017-09-01

The present article demonstrates the targeted delivery of doxorubicin hydrochloride to human osteosarcoma cancer cell lines (MG 63) using functionalized dextrin based crosslinked, pH responsive and biocompatible nanogel. The nanogel has been prepared through Michael-type addition reaction using dextrin (Dxt), N, N'-methylene bisacrylamide (MBA, as crosslinker), acrylic acid (AA, as monomer) and potassium persulfate (KPS, as initiator). The structure, composition, morphology of the nanogel have been explored using FTIR and 1 H NMR spectroscopy, XRD, TGA, DSC, CHN and AFM analyses. The TEM analysis confirmed that the size of nanogel appeared within 100nm, while DLS study indicates that the diameter of the nanogel remained between 113 and 126nm. The AFM study implied the porous morphology of the synthesized nanogel. The rheological study suggests the gel behaviour of the synthesized nanogel at 37±0.1°C. Difference in% swelling at pH 5.5 and 7.4 indicates pH-responsiveness of the nanogel. The in vitro cytocompatibility results ascertained that the nanogel is non-toxic to human mesenchymal stem cells (hMSCs). In vitro cellular uptake study confirmed that FITC-loaded nanogel can cross the cellular membrane and be well uptake by the cell cytoplasm. The nanogel could efficiently encapsulate doxorubicin hydrochloride (Dox) with the loading efficiency of 27±0.2% after 72h. The Dox-loaded nanogel demonstrates anti-cancer activity towards MG 63 cancer cells and release the encapsulated drug in a controlled way. Copyright © 2017 Elsevier Ltd. All rights reserved.

Health-promoting conversations-A novel approach to families experiencing critical illness in the ICU environment.

PubMed

Hollman Frisman, Gunilla; Wåhlin, Ingrid; Orvelius, Lotti; Ågren, Susanna

2018-02-01

To identify and describe the outcomes of a nurse-led intervention, "Health-promoting conversations with families," regarding family functioning and well-being in families with a member who was critically ill. Families who have a critically ill family member in an intensive care unit face a demanding situation, threatening the normal functioning of the family. Yet, there is a knowledge gap regarding family members' well-being during and after critical illness. The study used a qualitative inductive-descriptive design. Eight families participated in health-promoting conversations aimed to create a context for change related to the families' identified problems and resources. Fifteen qualitative interviews were conducted with 18 adults who participated in health-promoting conversations about a critical illness in the family. Eight participants were patients (six men, two women) and 10 were family members (two male partners, five female partners, one mother, one daughter, one female grandchild). The interviews were analysed by conventional content analysis. Family members experienced strengthened togetherness, a caring attitude and confirmation through health-promoting conversations. The caring and calming conversations were appreciated despite the reappearance of exhausting feelings. Working through the experience and being confirmed promoted family well-being. Health-promoting conversations were considered to be healing, as the family members take part in sharing each other's feelings, thoughts and experiences with the critical illness. Health-promoting conversations could be a simple and effective nursing intervention for former intensive care patients and their families in any cultural context. © 2017 John Wiley & Sons Ltd.

Disentangling the brain networks supporting affective speech comprehension.

PubMed

Hervé, Pierre-Yves; Razafimandimby, Annick; Vigneau, Mathieu; Mazoyer, Bernard; Tzourio-Mazoyer, Nathalie

2012-07-16

Areas involved in social cognition, such as the medial prefrontal cortex (mPFC) and the left temporo-parietal junction (TPJ) appear to be active during the classification of sentences according to emotional criteria (happy, angry or sad, [Beaucousin et al., 2007]). These two regions are frequently co-activated in studies about theory of mind (ToM). To confirm that these regions constitute a coherent network during affective speech comprehension, new event-related functional magnetic resonance imaging data were acquired, using the emotional and grammatical-person sentence classification tasks on a larger sample of 51 participants. The comparison of the emotional and grammatical tasks confirmed the previous findings. Functional connectivity analyses established a clear demarcation between a "Medial" network, including the mPFC and TPJ regions, and a bilateral "Language" network, which gathered inferior frontal and temporal areas. These findings suggest that emotional speech comprehension results from interactions between language, ToM and emotion processing networks. The language network, active during both tasks, would be involved in the extraction of lexical and prosodic emotional cues, while the medial network, active only during the emotional task, would drive the making of inferences about the sentences' emotional content, based on their meanings. The left and right amygdalae displayed a stronger response during the emotional condition, but were seldom correlated with the other regions, and thus formed a third entity. Finally, distinct regions belonging to the Language and Medial networks were found in the left angular gyrus, where these two systems could interface. Copyright © 2012 Elsevier Inc. All rights reserved.

Sequencing the transcriptome of milk production: milk trumps mammary tissue

PubMed Central

2013-01-01

Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

Novel fMRI working memory paradigm accurately detects cognitive impairment in multiple sclerosis.

PubMed

Nelson, Flavia; Akhtar, Mohammad A; Zúñiga, Edward; Perez, Carlos A; Hasan, Khader M; Wilken, Jeffrey; Wolinsky, Jerry S; Narayana, Ponnada A; Steinberg, Joel L

2017-05-01

Cognitive impairment (CI) cannot be diagnosed by magnetic resonance imaging (MRI). Functional magnetic resonance imaging (fMRI) paradigms, such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory (WM). Preliminary findings using I/DMT showed differences in blood oxygenation level dependent (BOLD) activation between impaired (MSCI, n = 12) and non-impaired (MSNI, n = 9) multiple sclerosis (MS) patients. The aim of the study was to confirm CI detection based on I/DMT BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and Expanded Disability Status Scale (EDSS) in magnitude of BOLD signal was also sought. A total of 50 patients (EDSS mean ( m) = 3.2, disease duration (DD) m = 12 years, and age m = 40 years) underwent the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) and I/DMT. Working memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. A total of 10 MSNI, 30 MSCI, and 4 borderline patients were included in the analyses. Analysis of variance (ANOVA) showed MSNI had significantly greater WMa than MSCI, in the left prefrontal cortex and left supplementary motor area ( p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas ( p = 0.005, 0.004, respectively). I/DMT-based BOLD activation detects CI in MS. Larger studies are needed to confirm these findings.

Synthesis, crystal structure and growth of a new inorganic- organic hybrid compound for nonlinear optical applications: Aquadiiodo (3-aminopropanoic acid) cadmium (II)

NASA Astrophysics Data System (ADS)

Boopathi, K.; Babu, S. Moorthy; Jagan, R.; Ramasamy, P.

2017-12-01

The new inorganic-organic hybrid material aquadiiodo (3-aminopropanoic acid) cadmium (II) [ADI (3-AP) Cd] has been successfully synthesized and good quality crystals have been grown by slow evaporation solution technique. The structure was determined by single crystal X-ray diffraction at room temperature. The compound crystallizes in monoclinic crystal system with centro symmetric space group P21/c and four molecules in the unit cell. The structure of the title compound was further confirmed by 1H and 13C nuclear magnetic resonance spectral analysis. FT-IR spectroscopy was used to confirm the presence of various functional groups in the compound. The transmittance and optical parameters of the crystal were studied by UV- Visible-NIR spectroscopy. The thermal stability of the grown crystal was evaluated using thermogravimetric and differential thermal analyses. Mechanical hardness has been identified by Vickers micro hardness study and work hardening coefficient was calculated. Dielectric measurement was carried out as a function of frequency and results are discussed. The growth mechanism of the crystal was assessed by chemical etching studies. The third-order nonlinear optical susceptibility of [ADI (3-AP) Cd] was derived using the Z-scan technique, and it was 3.24955 × 10-8 esu. The positive nonlinear refractive index 2.48505 × 10-11 m2/W, is an indication of self-defocusing optical nonlinearity of the sample. It is believed that the [ADI (3-AP) Cd] is a promising new candidate for developing efficient nonlinear optical and optical power limiting devices.

Analysis of nanopore arrangement of porous alumina layers formed by anodizing in oxalic acid at relatively high temperatures

NASA Astrophysics Data System (ADS)

Zaraska, Leszek; Stępniowski, Wojciech J.; Jaskuła, Marian; Sulka, Grzegorz D.

2014-06-01

Anodic aluminum oxide (AAO) layers were formed by a simple two-step anodization in 0.3 M oxalic acid at relatively high temperatures (20-30 °C) and various anodizing potentials (30-65 V). The effect of anodizing conditions on structural features of as-obtained oxides was carefully investigated. A linear and exponential relationships between cell diameter, pore density and anodizing potential were confirmed, respectively. On the other hand, no effect of temperature and duration of anodization on pore spacing and pore density was found. Detailed quantitative and qualitative analyses of hexagonal arrangement of nanopore arrays were performed for all studied samples. The nanopore arrangement was evaluated using various methods based on the fast Fourier transform (FFT) images, Delaunay triangulations (defect maps), pair distribution functions (PDF), and angular distribution functions (ADF). It was found that for short anodizations performed at relatively high temperatures, the optimal anodizing potential that results in formation of nanostructures with the highest degree of pore order is 45 V. No direct effect of temperature and time of anodization on the nanopore arrangement was observed.

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.

Structure–function characterization reveals new catalytic diversity in the galactose oxidase and glyoxal oxidase family

PubMed Central

Yin, DeLu (Tyler); Urresti, Saioa; Lafond, Mickael; Johnston, Esther M.; Derikvand, Fatemeh; Ciano, Luisa; Berrin, Jean-Guy; Henrissat, Bernard; Walton, Paul H.; Davies, Gideon J.; Brumer, Harry

2015-01-01

Alcohol oxidases, including carbohydrate oxidases, have a long history of research that has generated fundamental biological understanding and biotechnological applications. Despite a long history of study, the galactose 6-oxidase/glyoxal oxidase family of mononuclear copper-radical oxidases, Auxiliary Activity Family 5 (AA5), is currently represented by only very few characterized members. Here we report the recombinant production and detailed structure–function analyses of two homologues from the phytopathogenic fungi Colletotrichum graminicola and C. gloeosporioides, CgrAlcOx and CglAlcOx, respectively, to explore the wider biocatalytic potential in AA5. EPR spectroscopy and crystallographic analysis confirm a common active-site structure vis-à-vis the archetypal galactose 6-oxidase from Fusarium graminearum. Strikingly, however, CgrAlcOx and CglAlcOx are essentially incapable of oxidizing galactose and galactosides, but instead efficiently catalyse the oxidation of diverse aliphatic alcohols. The results highlight the significant potential of prospecting the evolutionary diversity of AA5 to reveal novel enzyme specificities, thereby informing both biology and applications. PMID:26680532

[Impact of obesity in the pathophysiology of degenerative disk disease and in the morbidity and outcome of lumbar spine surgery].

PubMed

Delgado-López, Pedro David; Castilla-Díez, José Manuel

Obesity (BMI>30Kg/m 2 ) is a pandemic with severe medical and financial implications. There is growing evidence that relates certain metabolic processes within the adipose tissue, preferentially abdominal fat, with a low-intensity chronic inflammatory state mediated by adipokines and other substances that favor disk disease and chronic low back pain. Obesity greatly conditions both the preoperative evaluation and the spinal surgical technique itself. Some meta-analyses have confirmed an increase of complications following lumbar spine surgery (mainly infections and venous thrombosis) in obese subjects. However, functional outcomes after lumbar spine surgery are favorable although inferior to the non-obese population, acknowledging that obese patients present with worse baseline function levels and the prognosis of conservatively treated obese cohorts is much worse. The impact of preoperative weight loss in spine surgery has not been prospectively studied in these patients. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Perceptual Training in Beach Volleyball Defence: Different Effects of Gaze-Path Cueing on Gaze and Decision-Making

PubMed Central

Klostermann, André; Vater, Christian; Kredel, Ralf; Hossner, Ernst-Joachim

2015-01-01

For perceptual-cognitive skill training, a variety of intervention methods has been proposed, including the so-called “color-cueing method” which aims on superior gaze-path learning by applying visual markers. However, recent findings challenge this method, especially, with regards to its actual effects on gaze behavior. Consequently, after a preparatory study on the identification of appropriate visual cues for life-size displays, a perceptual-training experiment on decision-making in beach volleyball was conducted, contrasting two cueing interventions (functional vs. dysfunctional gaze path) with a conservative control condition (anticipation-related instructions). Gaze analyses revealed learning effects for the dysfunctional group only. Regarding decision-making, all groups showed enhanced performance with largest improvements for the control group followed by the functional and the dysfunctional group. Hence, the results confirm cueing effects on gaze behavior, but they also question its benefit for enhancing decision-making. However, before completely denying the method’s value, optimisations should be checked regarding, for instance, cueing-pattern characteristics and gaze-related feedback. PMID:26648894

Medication information leaflets for patients: the further validation of an analytic linguistic framework.

PubMed

Clerehan, Rosemary; Hirsh, Di; Buchbinder, Rachelle

2009-01-01

While clinicians may routinely use patient information leaflets about drug therapy, a poorly conceived leaflet has the potential to do harm. We previously developed a novel approach to analysing leaflets about a rheumatoid arthritis drug, using an analytic approach based on systemic functional linguistics. The aim of the present study was to verify the validity of the linguistic framework by applying it to two further arthritis drug leaflets. The findings confirmed the applicability of the framework and were used to refine it. A new stage or 'move' in the genre was identified. While the function of many of the moves appeared to be 'to instruct' the patient, the instruction was often unclear. The role relationships expressed in the text were critical to the meaning. As with our previous study, judged on their lexical density, the leaflets resembled academic text. The framework can provide specific tools to assess and produce medication information leaflets to support readers in taking medication. Future work could utilize the framework to evaluate information on other treatments and procedures or on healthcare information more widely.

Development and Validation of the Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C)

PubMed Central

HUFFORD, BRADLEY J.; FASTENAU, PHILIP S.

2009-01-01

Although lowered awareness of abilities has been associated with poorer outcome in adults with neurological compromise, a dearth of research exists examining whether lowered awareness exists in younger populations. Using findings from recent literature and expert opinion, a 47-item Subjective Awareness of Neuropsychological Deficits Questionnaire for Children (SAND-C) was created to assess awareness of cognitive functioning in 6 domains (attention, psychomotor, visual-spatial, language, memory, and executive functioning). Confirmatory factor analysis (CFA) of the SAND-C was conducted on a sample consisting of 365 healthy children and 48 children with epilepsy. The SAND-C was found to have strong reliability. Factor analysis confirmed the a priori 6 factor model, but the 6-factor model was only marginally better than a more parsimonious 1-factor solution. Post-hoc exploratory factor analyses indicate that the SAND-C may measure more constructs for adolescents than for younger children. The difference between younger and older children may reflect developmental changes in metacognitive awareness and abstraction about their own abilities. PMID:15969352

Influence of geosmin-producing Streptomyces on the growth and volatile metabolites of yeasts during chinese liquor fermentation.

PubMed

Du, Hai; Lu, Hu; Xu, Yan

2015-01-14

Diverse Streptomyces species act as geosmin producers in the Chinese liquor-making process, causing an earthy, off-odor containment. Through microbiological and metabolite analyses, this paper investigates the influence of several geosmin-producing Streptomyces on the microbial community of a brewing system. The antifungal activity against functional liquor-brewing microbes was assayed by an agar diffusion method. Several Streptomyces, most notably Streptomyces sampsonii QC-2, inhibited the growth of the brewing functional yeasts and molds in pure culture. In a simulated coculture, Streptomyces spp. reduced the flavor compounds (alcohols and esters) contributed by yeasts. Nine components in Streptomyces sampsonii QC-2 broth were detected by ultraperformance liquid chromatography coupled with photo diode array (UPLC–PDA), with characteristic ultraviolet absorptions at 360, 380, and 400 nm. The main products of Streptomyces sampsonii QC-2 were identified by ultraperformance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF–MS/MS), and confirmed by standard mass spectrometry. The antifungal active components were revealed as a series of heptaene macrolide antibiotics.

Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis

PubMed Central

Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

2018-01-01

Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis. Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

The Tcp conjugation system of Clostridium perfringens.

PubMed

Wisniewski, Jessica A; Rood, Julian I

2017-05-01

The Gram-positive pathogen Clostridium perfringens possesses a family of large conjugative plasmids that is typified by the tetracycline resistance plasmid pCW3. Since these plasmids may carry antibiotic resistance genes or genes encoding extracellular or sporulation-associated toxins, the conjugative transfer of these plasmids appears to be important for the epidemiology of C. perfringens-mediated diseases. Sequence analysis of members of this plasmid family identified a highly conserved 35kb region that encodes proteins with various functions, including plasmid replication and partitioning. The tcp conjugation locus also was identified in this region, initially based on low-level amino acid sequence identity to conjugation proteins from the integrative conjugative element Tn916. Genetic studies confirmed that the tcp locus is required for conjugative transfer and combined with biochemical and structural analyses have led to the development of a functional model of the Tcp conjugation apparatus. This review summarises our current understanding of the Tcp conjugation system, which is now one of the best-characterized conjugation systems in Gram-positive bacteria. Copyright © 2017 Elsevier Inc. All rights reserved.

Corazonin Signaling Is Required in the Male for Sperm Transfer in the Oriental Fruit Fly Bactrocera dorsalis.

PubMed

Hou, Qiu-Li; Chen, Er-Hu; Jiang, Hong-Bo; Yu, Shuai-Feng; Yang, Pei-Jin; Liu, Xiao-Qiang; Park, Yoonseong; Wang, Jin-Jun; Smagghe, Guy

2018-01-01

Corazonin (Crz) is a widely distributed neuropeptide (or neurohormone) in insects with diverse physiological functions. The present study aimed to reveal the functions of Crz and its receptor (CrzR) in the regulation of sexual behavior and fertility in male Bactrocera dorsalis . Tissue-specific expression analyses showed that the BdCrz transcript was most abundant in the central nervous system (CNS), and the BdCrzR transcript was most abundant in both the fat body and CNS. Immunochemical localization confirmed that three pairs of Crz-immunoreactive neurons are located in the dorsolateral protocerebrum region of male adult brain. Importantly, RNAi-mediated Crz knockdown lengthened mating duration in males, and knockdown of Crz or CrzR strongly decreased male fertility in the following 3 days, while the courtship behavior and mating efficiency were not affected. The reduced number of sperm in the reproductive organs of mated females indicated that Crz knockdown in males reduced sperm transfer. The findings of this study indicate that Crz contributes to the reproductive physiology of the oriental fruit fly B. dorsalis by regulating sperm transfer in male adults.

A procedure for scaling sensory attributes based on multidimensional measurements: application to sensory sharpness of kitchen knives

NASA Astrophysics Data System (ADS)

Takatsuji, Toshiyuki; Tanaka, Ken-ichi

1996-06-01

A procedure is derived by which sensory attributes can be scaled as a function of various physical and/or chemical properties of the object to be tested. This procedure consists of four successive steps: (i) design and experiment, (ii) fabrication of specimens according to the design parameters, (iii) assessment of a sensory attribute using sensory evaluation and (iv) derivation of the relationship between the parameters and the sensory attribute. In these steps an experimental design using orthogonal arrays, analysis of variance and regression analyses are used strategically. When a specimen with the design parameters cannot be physically fabricated, an alternative specimen having parameters closest to the design is selected from a group of specimens which can be physically made. The influence of the deviation of actual parameters from the desired ones is also discussed. A method of confirming the validity of the regression equation is also investigated. The procedure is applied to scale the sensory sharpness of kitchen knives as a function of the edge angle and the roughness of the cutting edge.

Identification of Staphylococcal Nuclease Domain-containing 1 (SND1) as a Metadherin-interacting Protein with Metastasis-promoting Functions*

PubMed Central

Blanco, Mario Andres; Alečković, Maša; Hua, Yuling; Li, Tuo; Wei, Yong; Xu, Zhen; Cristea, Ileana M.; Kang, Yibin

2011-01-01

Metastasis is the deadliest and most poorly understood feature of malignant diseases. Recent work has shown that Metadherin (MTDH) is overexpressed in over 40% of breast cancer patients and promotes metastasis and chemoresistance in experimental models of breast cancer progression. Here we applied mass spectrometry-based screen to identify staphylococcal nuclease domain-containing 1 (SND1) as a candidate MTDH-interacting protein. After confirming the interaction between SND1 and MTDH, we tested the role of SND1 in breast cancer and found that it strongly promotes lung metastasis. SND1 was further shown to promote resistance to apoptosis and to regulate the expression of genes associated with metastasis and chemoresistance. Analyses of breast cancer clinical microarray data indicated that high expression of SND1 in primary tumors is strongly associated with reduced metastasis-free survival in multiple large scale data sets. Thus, we have uncovered SND1 as a novel MTDH-interacting protein and shown that it is a functionally and clinically significant mediator of metastasis. PMID:21478147

OsDOG, a gibberellin-induced A20/AN1 zinc-finger protein, negatively regulates gibberellin-mediated cell elongation in rice.

PubMed

Liu, Yaju; Xu, Yunyuan; Xiao, Jun; Ma, Qibin; Li, Dan; Xue, Zhen; Chong, Kang

2011-07-01

The A20/AN1 zinc-finger proteins (ZFPs) play pivotal roles in animal immune responses and plant stress responses. From previous gibberellin (GA) microarray data and A20/AN1 ZFP family member association, we chose Oryza sativa dwarf rice with overexpression of gibberellin-induced gene (OsDOG) to examine its function in the GA pathway. OsDOG was induced by gibberellic acid (GA(3)) and repressed by the GA-synthesis inhibitor paclobutrazol. Different transgenic lines with constitutive expression of OsDOG showed dwarf phenotypes due to deficiency of cell elongation. Additional GA(1) and real-time PCR quantitative assay analyses confirmed that the decrease of GA(1) in the overexpression lines resulted from reduced expression of GA3ox2 and enhanced expression of GA2ox1 and GA2ox3. Adding exogenous GA rescued the constitutive expression phenotypes of the transgenic lines. OsDOG has a novel function in regulating GA homeostasis and in negative maintenance of plant cell elongation in rice. Copyright © 2011 Elsevier GmbH. All rights reserved.

Genome-wide identification, classification, and expression analysis of the arabinogalactan protein gene family in rice (Oryza sativa L.)

PubMed Central

Zhao, Jie

2010-01-01

Arabinogalactan proteins (AGPs) comprise a family of hydroxyproline-rich glycoproteins that are implicated in plant growth and development. In this study, 69 AGPs are identified from the rice genome, including 13 classical AGPs, 15 arabinogalactan (AG) peptides, three non-classical AGPs, three early nodulin-like AGPs (eNod-like AGPs), eight non-specific lipid transfer protein-like AGPs (nsLTP-like AGPs), and 27 fasciclin-like AGPs (FLAs). The results from expressed sequence tags, microarrays, and massively parallel signature sequencing tags are used to analyse the expression of AGP-encoding genes, which is confirmed by real-time PCR. The results reveal that several rice AGP-encoding genes are predominantly expressed in anthers and display differential expression patterns in response to abscisic acid, gibberellic acid, and abiotic stresses. Based on the results obtained from this analysis, an attempt has been made to link the protein structures and expression patterns of rice AGP-encoding genes to their functions. Taken together, the genome-wide identification and expression analysis of the rice AGP gene family might facilitate further functional studies of rice AGPs. PMID:20423940

Nocturnal Eating: Association with Binge Eating, Obesity, and Psychological Distress

PubMed Central

Striegel-Moore, Ruth H.; Rosselli, Francine; Wilson, G. Terence; Perrin, Nancy; Harvey, Kate; DeBar, Lynn

2009-01-01

Objective To examine clinical correlates of nocturnal eating, a core behavioral symptom of night eating syndrome. Method Data from 285 women who had participated in a two-stage screening for binge eating were utilized. Women (n = 41) who reported one or more nocturnal eating episodes in the past 28 days on the Eating Disorder Examination and women who did not report nocturnal eating (n =244) were compared on eating disorder symptomatology, Body Mass Index (BMI), and on measures of psychosocial adjustment. Results Nocturnal eaters were significantly more likely to report binge eating and differed significantly from non-nocturnal eaters (with responses indicating greater disturbance) on weight and shape concern, eating concern, self-esteem, depression, and functional impairment, but not on BMI or dietary restraint. Group differences remained significant in analyses adjusting for binge eating. Conclusions This study confirms the association between nocturnal eating and binge eating previously found in treatment seeking samples yet also suggests that the elevated eating disorder symptoms and decreased psychosocial adjustment observed in nocturnal eaters is not simply a function of binge eating. PMID:19708071

Structural basis of dual Ca2+/pH regulation of the endolysosomal TRPML1 channel

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

Li, Minghui; Zhang, Wei K.; Benvin, Nicole M.

The activities of organellar ion channels are often regulated by Ca2+ and H+, which are present in high concentrations in many organelles. Here we report a structural element critical for dual Ca2+/pH regulation of TRPML1, a Ca2+-release channel crucial for endolysosomal function. TRPML1 mutations cause mucolipidosis type IV (MLIV), a severe lysosomal storage disorder characterized by neurodegeneration, mental retardation and blindness. We obtained crystal structures of the 213-residue luminal domain of human TRPML1 containing three missense MLIV-causing mutations. This domain forms a tetramer with a highly electronegative central pore formed by a novel luminal pore loop. Cysteine cross-linking and cryo-EMmore » analyses confirmed that this architecture occurs in the full-length channel. Structure–function studies demonstrated that Ca2+ and H+ interact with the luminal pore and exert physiologically important regulation. The MLIV-causing mutations disrupt the luminal-domain structure and cause TRPML1 mislocalization. Our study reveals the structural underpinnings of TRPML1's regulation, assembly and pathogenesis.« less

Optimization of Neuronal-Computer Interface

DTIC Science & Technology

2009-06-23

for the inhibitory neurotransmitter gamma-aminobutyric acid ( GABA ) receptor subunit as a general marker of inhibitory neurons (Beck et al., 1993...These analyses confirmed the presence of GABA -positive neurons (Fig. 4). Fig 4: Cultures contain inhibitory neurons. Cultures were subjected to double...immunofluorescent analyses for neurofilaments (anti-NF) using monoclonal antibody SMI-32 and a polyclonal antibody directed against the GABA receptor

Environmental Control on Microbial Turnover of Leaf Carbon in Streams – Ecological Function of Phototrophic-Heterotrophic Interactions

PubMed Central

Fabian, Jenny; Zlatanović, Sanja; Mutz, Michael; Grossart, Hans-Peter; van Geldern, Robert; Ulrich, Andreas; Gleixner, Gerd; Premke, Katrin

2018-01-01

In aquatic ecosystems, light availability can significantly influence microbial turnover of terrestrial organic matter through associated metabolic interactions between phototrophic and heterotrophic communities. However, particularly in streams, microbial functions vary significantly with the structure of the streambed, that is the distribution and spatial arrangement of sediment grains in the streambed. It is therefore essential to elucidate how environmental factors synergistically define the microbial turnover of terrestrial organic matter in order to better understand the ecological role of photo-heterotrophic interactions in stream ecosystem processes. In outdoor experimental streams, we examined how the structure of streambeds modifies the influence of light availability on microbial turnover of leaf carbon (C). Furthermore, we investigated whether the studied relationships of microbial leaf C turnover to environmental conditions are affected by flow intermittency commonly occurring in streams. We applied leaves enriched with a 13C-stable isotope tracer and combined quantitative and isotope analyses. We thereby elucidated whether treatment induced changes in C turnover were associated with altered use of leaf C within the microbial food web. Moreover, isotope analyses were combined with measurements of microbial community composition to determine whether changes in community function were associated with a change in community composition. In this study, we present evidence, that environmental factors interactively determine how phototrophs and heterotrophs contribute to leaf C turnover. Light availability promoted the utilization of leaf C within the microbial food web, which was likely associated with a promoted availability of highly bioavailable metabolites of phototrophic origin. However, our results additionally confirm that the structure of the streambed modifies light-related changes in microbial C turnover. From our observations, we conclude that the streambed structure influences the strength of photo-heterotrophic interactions by defining the spatial availability of algal metabolites in the streambed and the composition of microbial communities. Collectively, our multifactorial approach provides valuable insights into environmental controls on the functioning of stream ecosystems.

High-altitude forest sensitivity to global warming: results from long-term and short-term analyses in the eastern italian alps

NASA Astrophysics Data System (ADS)

Carrer, Marco; Anfodillo, Tommaso; Urbinati, Carlo; Carraro, Vinicio

Dendroecological (long-term) analysis and ecophysiological (short-term) monitoring were used interactively to study the responses of tree-ring growth to climate in timberline mixed forests (consisting of Larix decidua Mill., Picea abies (L.) Karst. and Pinus cembra (L.)) in the Italian Eastern Alps (2000-2100 m a.s.l.). Climate-growth linear response functions (LRF) revealed that warm temperatures in June and July have a positive effect on radial growth whereas precipitation during the vegetation period has no effect. Monitoring of the intra-annual radial growth dynamics using band dendrometers confirmed that the radial growth rate of the three species in June and July was greater when air temperatures were higher. Tree-ring formation lasted about 50-60 days (from mid-June to the beginning of August).

Deep and wide photometry of two open clusters NGC 1245 and NGC 2506: dynamical evolution and halo

NASA Astrophysics Data System (ADS)

Lee, S. H.; Kang, Y.-W.; Ann, H. B.

2013-06-01

We studied the structure of two old open clusters, NGC 1245 and NGC 2506, from a wide and deep VI photometry data acquired using the CFH12K CCD camera at Canada-France-Hawaii Telescope. We devised a new method for assigning cluster membership probability to individual stars using both spatial positions and positions in the colour-magnitude diagram. From analyses of the luminosity functions at several cluster-centric radii and the radial surface density profiles derived from stars with different luminosity ranges, we found that the two clusters are dynamically relaxed to drive significant mass segregation and evaporation of some fraction of low-mass stars. There seems to be a signature of tidal tail in NGC 1245 but the signal is too low to be confirmed.

279 - Xanes Studies on UV-Irradiated Interstellar Ice Analogs: A Comparison to STARDUST Samples

NASA Technical Reports Server (NTRS)

Milam, Stefanie N.; Cody, George D.; Kilcoyne, A. L. David; Nuevo, Michel; Sandford, Scott A.; Stroud, Rhonda M.; DeGregorio, Bradley T.

2010-01-01

We present C-, N-, and O-XANES (X-ray Absorption Near-Edge Spectroscopy) results of organic residues produced in the laboratory from the UV irradiation of astrophysical ice analogs containing H20, CO, CH30H, NH31 in order to mimic processes that may occur in cold icy bodies of the outer Solar System, particularly in comets, Such analyses showed that laboratory-formed organic residues mainly consist of a solid phase and an oily phase. C-XANES analysis of the solid phase suggests a rich distribution of organic functionalities, among which carbonyl groups, C=C bonds, and alcohols are present. Results from N-XANES indicate the possible presence of amide, amine, and nitrile groups, The O-XANES spectra confirmed the a-bearing groups, These results are compared with the XANES spectra obtained from STARDUST cometary samples,

Structural diversity of supercoiled DNA

PubMed Central

Irobalieva, Rossitza N.; Fogg, Jonathan M.; Catanese, Daniel J.; Sutthibutpong, Thana; Chen, Muyuan; Barker, Anna K.; Ludtke, Steven J.; Harris, Sarah A.; Schmid, Michael F.; Chiu, Wah; Zechiedrich, Lynn

2015-01-01

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function. PMID:26455586

Structural diversity of supercoiled DNA

NASA Astrophysics Data System (ADS)

Irobalieva, Rossitza N.; Fogg, Jonathan M.; Catanese, Daniel J.; Sutthibutpong, Thana; Chen, Muyuan; Barker, Anna K.; Ludtke, Steven J.; Harris, Sarah A.; Schmid, Michael F.; Chiu, Wah; Zechiedrich, Lynn

2015-10-01

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA minicircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function.

The theory precision analyse of RFM localization of satellite remote sensing imagery

NASA Astrophysics Data System (ADS)

Zhang, Jianqing; Xv, Biao

2009-11-01

The tradition method of detecting precision of Rational Function Model(RFM) is to make use of a great deal check points, and it calculates mean square error through comparing calculational coordinate with known coordinate. This method is from theory of probability, through a large number of samples to statistic estimate value of mean square error, we can think its estimate value approaches in its true when samples are well enough. This paper is from angle of survey adjustment, take law of propagation of error as the theory basis, and it calculates theory precision of RFM localization. Then take the SPOT5 three array imagery as experiment data, and the result of traditional method and narrated method in the paper are compared, while has confirmed tradition method feasible, and answered its theory precision question from the angle of survey adjustment.

Ureaplasma diversum in bull semen in Australia: its detection and potential effects.

PubMed

Hobson, N; Chousalkar, K K; Chenoweth, P J

2013-11-01

The primary objective of this study was to confirm the infection status of Ureaplasma diversum in Australian bulls and to identify morphological changes of sperm from U. diversum-positive bulls. Fresh semen samples were taken from 29 sexually active beef bulls from suspect herds in the Riverina/Upper Murray region. U. diversum was identified using PCR analyses and culture of the organism. Nine of the bulls were PCR-positive for U. diversum but none of these had genital lesions. Sperm from infected bulls showed increased incidence of abnormal tails (bent and coiled), as well as surface abnormalities (i.e. small protuberances or lumps). The results suggest impairment of sperm function and possibly fertility. Further investigations into the potential role of U. diversum as a pathogen for Australian cattle are warranted. © 2013 Australian Veterinary Association.

Fullerene-like Mo(W)(1-x)Re(x)S2 nanoparticles.

PubMed

Deepak, Francis Leonard; Popovitz-Biro, Ronit; Feldman, Yishay; Cohen, Hagai; Enyashin, Andrey; Seifert, Gotthard; Tenne, Reshef

2008-09-01

Inorganic fullerene-like (IF) Mo(1-x)Re(x)S(2) and W(1-x)Re(x)S(2) nanoparticles have been synthesized by a gas-phase reaction involving the respective metal halides with H(2)S. The IF-Mo(W)(1-x)Re(x)S(2) nanoparticles, containing up to 5 % Re, were characterized by a variety of experimental techniques. Analyses of the X-ray powder diffraction and different electron microscopy techniques show that the Re is doped in the MoS(2) host lattice. Interestingly, Re-doped MoS(2) nanotubes are present as well, although in small quantities ( approximately 5 %). XPS results confirm the nanoparticles to be more n-type arising from the effect of Re doping. Additionally, density-functional tight-binding (DFTB) calculations support the observed n-type behavior.

Organic field effect transistor composed by fullerene C60 and heterojunctions

NASA Astrophysics Data System (ADS)

Vasconcelos, Railson C.; Aleixo, Vicente F. P.; Del Nero, Jordan

2017-02-01

We present a study of the complex electronic behavior of a fullerene (C60) molecule attached to six leads (heterojunctions), which works as a three-dimension rectifier. In addition, we confirmed that the fullerene works not only as an electron donor, but also as barrier and transport channel to electrons through the molecule. Moreover, when the phenylpropanodinilla (PPP) lead is orthogonally subjected to bias voltage, the charge distribution and the current displays regions of saturation and resonance similar to semiconductor devices. In order to understand the electronic transport in the molecule, we applied non-equilibrium green function (NEGF) method and performed Fowler-Nordheim (FN) and Millikan-Lauritsen (ML) analyses. The ML curves proved to be sufficient to describe the FN characteristics. In this work, we report the theoretical design for electronic transport of a 3D device (6-terminal).

Transmission and reassortment of avian influenza viruses at the Asian-North American interface.

PubMed

Ramey, Andrew M; Pearce, John M; Ely, Craig R; Guy, Lisa M Sheffield; Irons, David B; Derksen, Dirk V; Ip, Hon S

2010-10-25

Twenty avian influenza viruses were isolated from seven wild migratory bird species sampled at St. Lawrence Island, Alaska. We tested predictions based on previous phylogenetic analyses of avian influenza viruses that support spatially dependent trans-hemispheric gene flow and frequent interspecies transmission at a location situated at the Asian-North American interface. Through the application of phylogenetic and genotypic approaches, our data support functional dilution by distance of trans-hemispheric reassortants and interspecific virus transmission. Our study confirms infection of divergent avian taxa with nearly identical avian influenza strains in the wild. Findings also suggest that H16N3 viruses may contain gene segments with unique phylogenetic positions and that further investigation of how host specificity may impact transmission of H13 and H16 viruses is warranted. Copyright © 2010. Published by Elsevier Inc.

Measuring pain phenomena after spinal cord injury: Development and psychometric properties of the SCI-QOL Pain Interference and Pain Behavior assessment tools.

PubMed

Cohen, Matthew L; Kisala, Pamela A; Dyson-Hudson, Trevor A; Tulsky, David S

2018-05-01

To develop modern patient-reported outcome measures that assess pain interference and pain behavior after spinal cord injury (SCI). Grounded-theory based qualitative item development; large-scale item calibration field-testing; confirmatory factor analyses; graded response model item response theory analyses; statistical linking techniques to transform scores to the Patient Reported Outcome Measurement Information System (PROMIS) metric. Five SCI Model Systems centers and one Department of Veterans Affairs medical center in the United States. Adults with traumatic SCI. N/A. Spinal Cord Injury - Quality of Life (SCI-QOL) Pain Interference item bank, SCI-QOL Pain Interference short form, and SCI-QOL Pain Behavior scale. Seven hundred fifty-seven individuals with traumatic SCI completed 58 items addressing various aspects of pain. Items were then separated by whether they assessed pain interference or pain behavior, and poorly functioning items were removed. Confirmatory factor analyses confirmed that each set of items was unidimensional, and item response theory analyses were used to estimate slopes and thresholds for the items. Ultimately, 7 items (4 from PROMIS) comprised the Pain Behavior scale and 25 items (18 from PROMIS) comprised the Pain Interference item bank. Ten of these 25 items were selected to form the Pain Interference short form. The SCI-QOL Pain Interference item bank and the SCI-QOL Pain Behavior scale demonstrated robust psychometric properties. The Pain Interference item bank is available as a computer adaptive test or short form for research and clinical applications, and scores are transformed to the PROMIS metric.

Experimental development of a new protocol for extraction and characterization of microplastics in fish tissues: First observations in commercial species from Adriatic Sea.

PubMed

Avio, Carlo Giacomo; Gorbi, Stefania; Regoli, Francesco

2015-10-01

The presence of microplastics in the marine environment has raised scientific interest during the last decade. Several organisms can ingest microplastics with potentially adverse effects on the digestive tract, respiratory system and locomotory appendages. However, a clear evidence of tissue accumulation and transfer of such microparticles in wild organisms is still lacking, partially hampered by technical difficulties in isolation and characterization protocols from biological samples. In this work, we compared the efficacy of some existing approaches and we optimized a new protocol allowing an extraction yield of microplastics from fish tissues ranging between 78% and 98%, depending on the polymer size. FT-IR analyses confirmed that the extraction procedure did not affect the particles characteristics. The method was further validated on the fish mullet, Mugil cephalus, exposed under laboratory conditions to polystyrene and polyethylene; the particles were isolated and quantified in stomach and liver, and their presence in the hepatic tissue was confirmed also by histological analyses. A preliminary characterization revealed the presence and distribution of microplastics in various fish species collected along the Adriatic Sea. FT-IR analyses indicated polyethylene as the predominant polymer (65%) in the stomach of fish. The overall results confirmed the newly developed method as a reliable approach to detect and quantify microplastics in the marine biota. Copyright © 2015 Elsevier Ltd. All rights reserved.