Acute responsivity of the serotonergic system to S-citalopram and positive emotionality : the moderating role of the 5-HTTLPR

According to the idea that the central serotonergic system has a modulatory function on behavior and personality in general, we aimed to highlight its association to habitual positive emotionality. In a placebo-controlled double-blind and randomized cross-over neuroendocrine challenge design (n = 72 healthy males) we investigated the association of the central serotonergic responsivity, 5-HTTLPR-genotype as well as their combined effects on positive emotionality. Regression analyses revealed an involvement of the serotonergic system in positive emotionality. There was, however, no direct association between positive emotionality and cortisol responses to S-citalopram; rather 5-HTTLPR-genotype showed an association (p < 0.05). That is, positive emotionality scores increased with the number of s-alleles carried by the individuals. Most notable was the moderating role of 5-HTTLPR-genotype (p < 0.05) on the association between acute serotonergic responsivity and positive emotionality. Indeed, this association was only found in ss-homozygotes, in which the acute responsivity of the serotonergic system additionally seems to contribute to the level of positive emotionality (r = 0.70, p < 0.05). The findings correspond to previous research demonstrating that the 5-HTTLPR is not only involved in the negative-emotional aspects of behavior and temperament, but is associated, moreover, with positive affectivity—supporting the assumption of its valence-neutrality. In addition, our data are in line with the idea of possible influences of the 5-HTTLPR-genotype on early neuronal development. They also indicate the need for further studies in order to clearly elucidate the role of the serotonergic system and its subcomponents in the regulation of positive emotionality

Assessment of Different Expression Strategies for the Production of a Recombinant Lipoprotein Vaccine in Plants

The ability of plants to serve as a production system for bacterial lipoprotein vaccines has been investigated. First, the effect of high-level expression of the Borrelia burgdorferi outer membrane protein A (OspA), a prototype vaccine against Lyme disease, has been examined by a proteomics approach. Analysis by 2D-PAGE of wild type tobacco plants and transplastomic plants accumulating recombinant OspA showed no apparent differences in protein pattern except for OspA. However, presence of the bacterial signal sequence limits transgene accumulation. As an alternative approach OspA was produced in Nicotiana benthamiana plants by transient expression via a deconstructed tobacco mosaic virus-based system. While rapid expression of OspA could be achieved, no palmitoylation occurred with the genuine bacterial sequence. In contrast, modification of the N-terminus with an eukaryotic sequence motif resulted in palmitoylation of OspA. This study shows that plants provide multiple expression strategies and could serve as a versatile production platform for recombinant lipidated subunit vaccines

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Arabidopsis MSI1 functions in photoperiodic flowering time control

Appropriate timing of flowering is crucial for crop yield and the reproductive success of plants. Flowering can be induced by a number of molecular pathways that respond to internal and external signals such as photoperiod, vernalization or light quality, ambient temperature and biotic as well as abiotic stresses. The key florigenic signal FLOWERING LOCUS T (FT) is regulated by several flowering activators, such as CONSTANS (CO), and repressors, such as FLOWERING LOCUS C (FLC). Chromatin modifications are essential for regulated gene expression, which often involves the well conserved MULTICOPY SUPRESSOR OF IRA 1 (MSI1)-like protein family. MSI1-like proteins are ubiquitous partners of various complexes, such as POLYCOMB REPRESSIVE COMPLEX2 or CHROMATIN ASSEMBLY FACTOR 1. In Arabidopsis, one of the functions of MSI1 is to control the switch to flowering. Arabidopsis MSI1 is needed for the correct expression of the floral integrator gene SUPPRESSOR OF CO 1 (SOC1). Here, we show that the histone-binding protein MSI1 acts in the photoperiod pathway to regulate normal expression of CO in long day (LD) photoperiods. Reduced expression of CO in msi1-mutants leads to failure of FT and SOC1 activation and to delayed flowering. MSI1 is needed for normal sensitivity of Arabidopsis to photoperiod, because msi1-mutants responded less than wild type to an intermittent LD treatment of plants grown in short days. Finally, genetic analysis demonstrated that MSI1 acts upstream of the CO-FT pathway to enable an efficient photoperiodic response and to induce flowering.ISSN:1664-462

Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.

BACKGROUND: Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. METHODS: Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. RESULTS: Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. CONCLUSIONS: We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective

Arabidopsis MSI1 connects LHP1 to PRC2 complexes

Polycomb group (PcG) proteins form essential epigenetic memory systems for controlling gene expression during development in plants and animals. However, the mechanism of plant PcG protein functions remains poorly understood. Here, we probed the composition and function of plant Polycomb repressive complex 2 (PRC2). This work established the fact that all known plant PRC2 complexes contain MSI1, a homologue of Drosophila p55. While p55 is not essential for the in vitro enzymatic activity of PRC2, plant MSI1 was required for the functions of the EMBRYONIC FLOWER and the VERNALIZATION PRC2 complexes including trimethylation of histone H3 Lys27 (H3K27) at the target chromatin, as well as gene repression and establishment of competence to flower. We found that MSI1 serves to link PRC2 to LIKE HETEROCHROMATIN PROTEIN 1 (LHP1), a protein that binds H3K27me3 in vitro and in vivo and is required for a functional plant PcG system. The LHP1-MSI1 interaction forms a positive feedback loop to recruit PRC2 to chromatin that carries H3K27me3. Consequently, this can provide a mechanism for the faithful inheritance of local epigenetic information through replication

Salivary cortisol concentrations.

<p>Means and SEMs of differences from baseline of salivary cortisol concentrations (Δ = difference from baseline). Repeated Measures Analyses of Covariance reveal a significant Cyberball x time interaction (F = 3.771; p = .013). For baseline value see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0060433#pone-0060433-t001" target="_blank">Table 1</a>.</p

Assessment of dependent variables during the experiment.

<p>Assessment of blood and saliva samples, subjective mood and needs is indicated by a •. Abbreviations: C = placing the catheter; RP = rest period;CB = Cyberball; PS = poststress period; DB = debriefing.</p

Mood after Cyberball and after public speaking.

1<p>Multidimensional Mood Questionnaire;</p>2<p>Differential Affect Scale;</p>3<p>with baseline, baseline estradiol and time of experiment as covariates.</p