Serum homocysteine is weakly associated with von Willebrand factor and soluble vascular cell adhesion molecule 1, but not with C-reactive protein in type 2 diabetic and nondiabetic subjects: the Hoorn Study.

Background: Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations. Materials and Methods: Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations. Results: After adjustment for confounders, tHcy was significantly but weakly associated with vWf (β=0·15, P=0·05) and sVCAM-1 (β=0·082, P=0·04). tHcy was not significantly associated with CRP (β=0·02, P=0·91). The presence of diabetes did not significantly modify these associations. Conclusions: This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP

Emotion based attentional priority for storage in visual short-term memory

A plethora of research demonstrates that the processing of emotional faces is prioritised over non-emotive stimuli when cognitive resources are limited (this is known as ‘emotional superiority’). However, there is debate as to whether competition for processing resources results in emotional superiority per se, or more specifically, threat superiority. Therefore, to investigate prioritisation of emotional stimuli for storage in visual short-term memory (VSTM), we devised an original VSTM report procedure using schematic (angry, happy, neutral) faces in which processing competition was manipulated. In Experiment 1, display exposure time was manipulated to create competition between stimuli. Participants (n = 20) had to recall a probed stimulus from a set size of four under high (150 ms array exposure duration) and low (400 ms array exposure duration) perceptual processing competition. For the high competition condition (i.e. 150 ms exposure), results revealed an emotional superiority effect per se. In Experiment 2 (n = 20), we increased competition by manipulating set size (three versus five stimuli), whilst maintaining a constrained array exposure duration of 150 ms. Here, for the five-stimulus set size (i.e. maximal competition) only threat superiority emerged. These findings demonstrate attentional prioritisation for storage in VSTM for emotional faces. We argue that task demands modulated the availability of processing resources and consequently the relative magnitude of the emotional/threat superiority effect, with only threatening stimuli prioritised for storage in VSTM under more demanding processing conditions. Our results are discussed in light of models and theories of visual selection, and not only combine the two strands of research (i.e. visual selection and emotion), but highlight a critical factor in the processing of emotional stimuli is availability of processing resources, which is further constrained by task demands

Feasibility, reliability and validity of a questionnaire on healthcare consumption and productivity loss in patients with a psychiatric disorder (TiC-P)

Background: Patient self-report allows collecting comprehensive data for the purpose of performing economic evaluations. The aim of the current study was to assess the feasibility, reliability and a part of the construct validity of a commonly applied questionnaire on healthcare utilization and productivity losses in patients with a psychiatric disorder (TiC-P). Methods. Data were derived alongside two clinical trials performed in the Netherlands in patients with mental health problems. The response rate, average time of filling out the questionnaire and proportions of missing values were used as indicators of feasibility of the questionnaire. Test-retest analyses were performed including Cohen's kappa and intra class correlation coefficients to assess reliability of the data. The construct validity was assessed by comparing patient reported data on contacts with psychotherapists and reported data on long-term absence from work with data derived from registries. Results: The response rate was 72%. The mean time needed for filling out the first TiC-P was 9.4 minutes. The time needed for filling out the questionnaire was 2.3 minutes less for follow up measurements. Proportions of missing values were limited (< 2.4%) except for medication for which in 10% of the cases costs could not be calculated. Cohen's kappa was satisfactory to almost perfect for most items related to healthcare consumption and satisfactory for items on absence from work and presenteeism. Comparable results were shown by the ICCs on variables measuring volumes of medical consumption and productivity losses indicating good reliability of the questionnaire. Absolute agreement between patient-reported data and data derived from medical registrations of the psychotherapists was satisfactory. Accepting a margin o

Exploratory analysis of protein translation regulatory networks using hierarchical random graphs

Abstract Background Protein translation is a vital cellular process for any living organism. The availability of interaction databases provides an opportunity for researchers to exploit the immense amount of data in silico such as studying biological networks. There has been an extensive effort using computational methods in deciphering the transcriptional regulatory networks. However, research on translation regulatory networks has caught little attention in the bioinformatics and computational biology community. Results In this paper, we present an exploratory analysis of yeast protein translation regulatory networks using hierarchical random graphs. We derive a protein translation regulatory network from a protein-protein interaction dataset. Using a hierarchical random graph model, we show that the network exhibits well organized hierarchical structure. In addition, we apply this technique to predict missing links in the network. Conclusions The hierarchical random graph mode can be a potentially useful technique for inferring hierarchical structure from network data and predicting missing links in partly known networks. The results from the reconstructed protein translation regulatory networks have potential implications for better understanding mechanisms of translational control from a system’s perspective

Characterization of the Tomato ARF Gene Family Uncovers a Multi-Levels Post-Transcriptional Regulation Including Alternative Splicing

Background: The phytohormone auxin is involved in a wide range of developmental processes and auxin signaling is known to modulate the expression of target genes via two types of transcriptional regulators, namely, Aux/IAA and Auxin Response Factors (ARF). ARFs play a major role in transcriptional activation or repression through direct binding to the promoter of auxin-responsive genes. The present study aims at gaining better insight on distinctive structural and functional features among ARF proteins. Results: Building on the most updated tomato (Solanum lycopersicon) reference genome sequence, a comprehensive set of ARF genes was identified, extending the total number of family members to 22. Upon correction of structural annotation inconsistencies, renaming the tomato ARF family members provided a consensus nomenclature for all ARF genes across plant species. In silico search predicted the presence of putative target site for small interfering RNAs within twelve Sl-ARFs while sequence analysis of the 59-leader sequences revealed the presence of potential small uORF regulatory elements. Functional characterization carried out by transactivation assay partitioned tomato ARFs into repressors and activators of auxin-dependent gene transcription. Expression studies identified tomato ARFs potentially involved in the fruit set process. Genome-wide expression profiling using RNA-seq revealed that at least one third of the gene family members display alternative splicing mode of regulation during the flower to fruit transition. Moreover, the regulation of several tomato ARF genes by both ethylene and auxin, suggests their potential contribution to the convergence mechanism between the signaling pathways of these two hormones. Conclusion: All together, the data bring new insight on the complexity of the expression control of Sl-ARF genes at the transcriptional and post-transcriptional levels supporting the hypothesis that these transcriptional mediators might represent one of the main components that enable auxin to regulate a wide range of physiological processes in a highly specific and coordinated manner

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Malaria and Fetal Growth Alterations in the 3(rd) Trimester of Pregnancy: A Longitudinal Ultrasound Study.

Pregnancy associated malaria is associated with decreased birth weight, but in-utero evaluation of fetal growth alterations is rarely performed. The objective of this study was to investigate malaria induced changes in fetal growth during the 3(rd) trimester using trans-abdominal ultrasound. An observational study of 876 pregnant women (398 primi- and secundigravidae and 478 multigravidae) was conducted in Tanzania. Fetal growth was monitored with ultrasound and screening for malaria was performed regularly. Birth weight and fetal weight were converted to z-scores, and fetal growth evaluated as fetal weight gain from the 26th week of pregnancy. Malaria infection only affected birth weight and fetal growth among primi- and secundigravid women. Forty-eight of the 398 primi- and secundigravid women had malaria during pregnancy causing a reduction in the newborns z-score of -0.50 (95% CI: -0.86, -0.13, P = 0.008, multiple linear regression). Fifty-eight percent (28/48) of the primi- and secundigravidae had malaria in the first half of pregnancy, but an effect on fetal growth was observed in the 3(rd) trimester with an OR of 4.89 for the fetal growth rate belonging to the lowest 25% in the population (95%CI: 2.03-11.79, P<0.001, multiple logistic regression). At an individual level, among the primi- and secundigravidae, 27% experienced alterations of fetal growth immediately after exposure but only for a short interval, 27% only late in pregnancy, 16.2% persistently from exposure until the end of pregnancy, and 29.7% had no alterations of fetal growth. The effect of malaria infections was observed during the 3(rd) trimester, despite infections occurring much earlier in pregnancy, and different mechanisms might operate leading to different patterns of growth alterations. This study highlights the need for protection against malaria throughout pregnancy and the recognition that observed changes in fetal growth might be a consequence of an infection much earlier in pregnancy.\u

Dendritic Morphology of Hippocampal and Amygdalar Neurons in Adolescent Mice Is Resilient to Genetic Differences in Stress Reactivity

Many studies have shown that chronic stress or corticosterone over-exposure in rodents leads to extensive dendritic remodeling, particularly of principal neurons in the CA3 hippocampal area and the basolateral amygdala. We here investigated to what extent genetic predisposition of mice to high versus low stress reactivity, achieved through selective breeding of CD-1 mice, is also associated with structural plasticity in Golgi-stained neurons. Earlier, it was shown that the highly stress reactive (HR) compared to the intermediate (IR) and low (LR) stress reactive mice line presents a phenotype, with respect to neuroendocrine parameters, sleep architecture, emotional behavior and cognition, that recapitulates some of the features observed in patients suffering from major depression. In late adolescent males of the HR, IR, and LR mouse lines, we observed no significant differences in total dendritic length, number of branch points and branch tips, summated tip order, number of primary dendrites or dendritic complexity of either CA3 pyramidal neurons (apical as well as basal dendrites) or principal neurons in the basolateral amygdala. Apical dendrites of CA1 pyramidal neurons were also unaffected by the differences in stress reactivity of the animals; marginally higher length and complexity of the basal dendrites were found in LR compared to IR but not HR mice. In the same CA1 pyramidal neurons, spine density of distal apical tertiary dendrites was significantly higher in LR compared to IR or HR animals. We tentatively conclude that the dendritic complexity of principal hippocampal and amygdala neurons is remarkably stable in the light of a genetic predisposition to high versus low stress reactivity, while spine density seems more plastic. The latter possibly contributes to the behavioral phenotype of LR versus HR animals