Universal features of personality traits from the observer's perspective: Data from 50 cultures

To test hypotheses about the universality of personality traits, college students in 50 cultures identified an adult or college-aged man or woman whom they knew well and rated the 11,985 targets using the 3rd-person version of the Revised NEO Personality Inventory. Factor analyses within cultures showed that the normative American self-report structure was clearly replicated in most cultures and was recognizable in all. Sex differences replicated earlier self-report results, with the most pronounced differences in Western cultures. Cross-sectional age differences for 3 factors followed the pattern identified in self-reports, with moderate rates of change during college age and slower changes after age 40. With a few exceptions, these data support the hypothesis that features of personality traits are common to all human groups.

Development of a T Cell Receptor Targeting an HLA-A*0201 Restricted Epitope from the Cancer-Testis Antigen SSX2 for Adoptive Immunotherapy of Cancer.

The clinical success of adoptive immunotherapy of cancer relies on the selection of target antigens that are highly expressed in tumor cells but absent in essential normal tissues. A group of genes that encode the cancer/testis or cancer germline antigens have been proposed as ideal targets for immunotherapy due to their high expression in multiple cancer types and their restricted expression in immunoprivileged normal tissues. In the present work we report the isolation and characterization of human T cell receptors (TCRs) with specificity for synovial sarcoma X breakpoint 2 (SSX2), a cancer/testis antigen expressed in melanoma, prostate cancer, lymphoma, multiple myeloma and pancreatic cancer, among other tumors. We isolated seven HLA-A2 restricted T cell receptors from natural T cell clones derived from tumor-infiltrated lymph nodes of two SSX2-seropositive melanoma patients, and selected four TCRs for cloning into retroviral vectors. Peripheral blood lymphocytes (PBL) transduced with three of four SSX2 TCRs showed SSX241-49 (KASEKIFYV) peptide specific reactivity, tumor cell recognition and tetramer binding. One of these, TCR-5, exhibited tetramer binding in both CD4 and CD8 cells and was selected for further studies. Antigen-specific and HLA-A*0201-restricted interferon-γ release, cell lysis and lymphocyte proliferation was observed following culture of TCR engineered human PBL with relevant tumor cell lines. Codon optimization was found to increase TCR-5 expression in transduced T cells, and this construct has been selected for development of clinical grade viral vector producing cells. The tumor-specific pattern of expression of SSX2, along with the potent and selective activity of TCR-5, makes this TCR an attractive candidate for potential TCR gene therapy to treat multiple cancer histologies.

Clinical outcome following combination of cutting balloon angioplasty and coronary β-radiation for in-stent restenosis : a report from the RENO registry

RESUME : Actuellement la brachythérapie endovasculaire reste le seul traitement efficace pour la resténose intrastent. Malgré ceci, la limitation majeure de cette technique est la resténose aux extrémités du stent (effet de bord) due à une couverture incomplète par la source radioactive (geographical miss). Le ballon coupant et qui ne glisse pas pourrait limiter le barotraumatisme engendré par la dilatation et qui avec la diminution de la radiation aux extrémités de la source radioactive, est à la base du geographical miss. Cette étude prospective a pour but d'examiner l'efficacité du traitement de la resténose intrastent par la combinaison d'angioplastie avec cutting ballon et β - irradiation. Le registre « Radiation in Europe NOvoste » (RENO) inclut tous les patients traités par β - irradiation coronaire avec le système Beta-CathTM System (Novoste Corporation, Brussels, Belgium) n'ayant pas été inclus dans une autre étude randomisée. Un premier sous-groupe de ces patients (groupe 1, n=166), représente les patients traités par cutting ballon et β - irradiation intra coronaire. Ce groupe a été défini d'une manière prospective et les résultats cliniques à 6 mois ont été comparés par rapport aux autres patients qui ont reçu un traitement par dilatation coronaire conventionnelle et β - irradiation (groupe 2, n=712). A 6 mois de suivi, on a retrouvé une différence significative entre les 2 groupes par rapport à la nécessité d'une nouvelle revascularisation du vaisseau préalablement traité (10,2% de récidive dans le groupe 1 contre 16,6 % dans le groupe 2 , p=0,04). Le nombre d'événements cardiaques majeurs (mortalité, infarctus du myocarde et revascularisation) a également été diminué de manière significative (10,8% contre 19,2% ; />=0,01). Cette observation a été confirmée par une analyse multivariée qui indique un risque diminué pour les événements cardiaques majeurs à 6 mois, (rapport de côtes : 0,49 ; intervalle de confiance 0,27-0,88 ; p=0,02). Comparé à l'angioplastie coronarienne avec ballon conventionnel, l'utilisation de cutting ballon avant la β - irradiation dans le traitement de la resténose intrastent démontre une meilleure évolution clinique à 6 mois. ABSTRACT: At present, vascular brachytherapy is the only efficient therapy for in-stent restenosis. Nevertheless edge restenosis often relat¬ed to geographical miss has been identified as a major limitation of the technique. The non-slippery cutting balloon has the potential to limit vascular barotraumas which, together with low-dose irradiation at both ends of the radioactive source, are the prerequisite for geographical miss. This prospective study aimed to examine the efficacy of combining cut¬ting balloon angioplasty and brachytherapy for in-stent restenosis. The Radiation in Europe NOvoste (RENO) registry prospectively tracked all patients who had been treated by coronary β-radiation with the Beta-CathTM System (Novoste Corporation. Brussels, Belgium) but were not included in a randomized radiation trial, A subgroup of patients with in-stent restenosis treated by cutting balloon angioplasty and coronary β-radiation (group 1, n = 166) was prospectively defined, and clinical outcomes of patients at 6 months were compared with those of patients treated by conventional angioplasty and coronary β -radiation (group 2, n = 712). At 6-month follow-up, there was a significant difference between groups 1 and 2 in- target vessel revascularization (10.2% versus 16.6% respectively; p = 0.04) and in the incidence of major adverse clinical events (MACE) including, death, myocardial infarction, and revascularization (10.8% versus 19.2%; p= 0.01). This observation was confirmed by a multivariate analysis indicating a. lower risk for MACE at 6 months (odds ratio: 0.49; confidence intervals: 0.27-0.88; p = 0.02). Compared to conventional angioplasty, cutting balloon angio¬plasty prior to coronary beta-radiation with the Beta-CathTM System seems to improve the 6-month clinical outcome in patients with in-stent restenosis.

Effect of Emotion and Personality on Deviation from Purely Rational Decision-Making

Human decision-making has consistently demonstrated deviation from "pure" rationality. Emotions are a primary driver of human actions and the current study investigates how perceived emotions and personality traits may affect decision-making during the Ultimatum Game (UG). We manipulated emotions by showing images with emotional connotation while participants decided how to split money with a second player. Event-related potentials (ERPs) from scalp electrodes were recorded during the whole decision-making process. We observed significant differences in the activity of central and frontal areas when participants offered money with respect to when they accepted or rejected an offer. We found that participants were more likely to offer a higher amount of money when making their decision in association with negative emotions. Furthermore, participants were more likely to accept offers when making their decision in association with positive emotions. Honest, conscientious, and introverted participants were more likely to accept offers. Our results suggest that factors others than a rational strategy may predict economic decision-making in the UG.

Electron microscopy of RecA-DNA complexes: Two different states, their functional significance and relation to the solved crystal structure

Seven different electron microscopy techniques habe been employed to study the RecA protein of E. coli. This review provides a summary of the conclusions that have been drawn from these studies, and attempts to relate these observations to models for the role of RecA protein in homologous recombination.

Chemokines in neuroectodermal cancers: the crucial growth signal from the soil.

Although chemokines and their receptors were initially identified as regulators of cell trafficking during inflammation and immune response, they have emerged as crucial players in all stages of tumor development, primary growth, migration, angiogenesis, and establishment as metastases in distant target organs. Neuroectodermal tumors regroup neoplasms originating from the embryonic neural crest cells, which display clinical and biological similarities. These tumors are highly malignant and rapidly progressing diseases that disseminate to similar target organs such as bone marrow, bone, liver and lungs. There is increasing evidence that interaction of several chemokine receptors with corresponding chemokine ligands are implicated in the growth and invasive characteristics of these tumors. In this review we summarize the current knowledge on the role of CXCL12 chemokine and its CXCR4 and CXCR7 receptors in the progression and survival of neuroectodermal tumors, with particular emphasis on neuroblastoma, the most typical and enigmatic neuroectodermal childhood tumor.

Long-term data from the swiss pulmonary hypertension registry.

BACKGROUND: Registries are important for real-life epidemiology on different pulmonary hypertension (PH) groups. OBJECTIVE: To provide long-term data of the Swiss PH registry of 1998-2012. METHODS: PH patients have been classified into 5 groups and registered upon written informed consent at 5 university and 8 associated hospitals since 1998. New York Heart Association (NYHA) class, 6-min walk distance, hemodynamics and therapy were registered at baseline. Patients were regularly followed, and therapy and events (death, transplantation, endarterectomy or loss to follow-up) registered. The data were stratified according to the time of diagnosis into prevalent before 2000 and incident during 2000-2004, 2005-2008 and 2009-2012. RESULTS: From 996 (53% female) PH patients, 549 had pulmonary arterial hypertension (PAH), 36 PH due to left heart disease, 127 due to lung disease, 249 to chronic thromboembolic PH (CTEPH) and 35 to miscellaneous PH. Age and BMI significantly increased over time, whereas hemodynamic severity decreased. Overall, event-free survival was 84, 72, 64 and 58% for the years 1-4 and similar for time periods since 2000, but better during the more recent periods for PAH and CTEPH. Of all PAH cases, 89% had target medical therapy and 43% combination therapy. Of CTEPH patients, 14 and 2% underwent pulmonary endarterectomy or transplantation, respectively; 87% were treated with PAH target therapy. CONCLUSION: Since 2000, the incident Swiss PH patients registered were older, hemodynamically better and mostly treated with PAH target therapies. Survival has been better for PAH and CTEPH diagnosed since 2008 compared with earlier diagnosis or other classifications.

Self-Expanding Versus Balloon-Expandable Stents in Acute Myocardial Infarction: Results From the APPOSITION II Study: Self-Expanding Stents in ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: This study sought to investigate whether self-expanding stents are more effective than balloon-expandable stents for reducing stent malapposition at 3 days after implantation in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. BACKGROUND: Acute myocardial infarction is associated with vasoconstriction and large thrombus burden. Resolution of vasoconstriction and thrombus load during the first hours to days after primary percutaneous coronary intervention may lead to stent undersizing and malapposition, which may subsequently lead to stent thrombosis or restenosis. In addition, aggressive stent deployment may cause distal embolization. METHODS: Eighty patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomized to receive a self-expanding stent (STENTYS, STENTYS SA, Paris, France) (n = 43) or a balloon-expandable stent (VISION, Abbott Vascular, Santa Clara, California; or Driver, Medtronic, Minneapolis, Minnesota) (n = 37) at 9 European centers. The primary endpoint was the proportion of stent strut malapposition at 3 days after implantation measured by optical coherence tomography. Secondary endpoints included major adverse cardiac events (cardiac death, recurrent myocardial infarction, emergent bypass surgery, or clinically driven target lesion revascularization). RESULTS: At 3 days after implantation, on a per-strut basis, a lower rate of malapposed stent struts was observed by optical coherence tomography in the self-expanding stent group than in the balloon-expandable group (0.58% vs. 5.46%, p < 0.001). On a per-patient basis, none of the patients in the self-expanding stent group versus 28% in the balloon-expandable group presented ≥5% malapposed struts (p < 0.001). At 6 months, major adverse cardiac events were 2.3% versus 0% in the self-expanding and balloon-expandable groups, respectively (p = NS). CONCLUSIONS: Strut malapposition at 3 days is significantly lower in ST-segment elevation myocardial infarction patients allocated to self-expanding stents when than in those allocated to balloon-expandable stents. The impact of this difference on clinical outcome and the risk of late stent thrombosis need to be evaluated further. (Randomized Comparison Between the STENTYS Self-expanding Coronary Stent and a Balloon-expandable Stent in Acute Myocardial Infarction [APPOSITION II]; NCT01008085).

Meta-analysis of estrogen response in MCF-7 distinguishes early target genes involved in signaling and cell proliferation from later target genes involved in cell cycle and DNA repair.

ABSTRACT: BACKGROUND: Many studies have been published outlining the global effects of 17 beta-estradiol (E2) on gene expression in human epithelial breast cancer derived MCF-7 cells. These studies show large variation in results, reporting between ~100 and ~1500 genes regulated by E2, with poor overlap. RESULTS: We performed a meta-analysis of these expression studies, using the Rank product method to obtain a more accurate and stable list of the differentially expressed genes, and of pathways regulated by E2. We analyzed 9 time-series data sets, concentrating on response at 3-4 hrs (early) and at 24 hrs (late). We found >1000 statistically significant probe sets after correction for multiple testing at 3-4 hrs, and >2000 significant probe sets at 24 hrs. Differentially expressed genes were examined by pathway analysis. This revealed 15 early response pathways, mostly related to cell signaling and proliferation, and 20 late response pathways, mostly related to breast cancer, cell division, DNA repair and recombination. CONCLUSIONS: Our results show that meta-analysis identified more differentially expressed genes than the individual studies, and that these genes act together in networks. These results provide new insight into E2 regulated mechanisms, especially in the context of breast cancer.

Alkoholismus aus systemischer Sicht [Alcoholism from the systemic viewpoint].

In this paper we attempt to view the phenomenon alcohol abuse and dependence within the family or partnership and to describe the important impact of alcoholism on social relation. Understating the role of alcohol in the familial structure may help to draw conclusions for competence and effectiveness of individual or familial psychotherapeutic interventions.

Clinical usefulness of therapeutic concentration monitoring for imatinib dosage individualization: Results from the randomized controlled I-COME Trial

Introduction: Imatinib trough plasma concentrations (Cmin) have been correlated with treatment response in chronic myeloid leukemia (CML) patients. The use of Cmin monitoring for optimizing imatinib dosage (therapeutic drug monitoring [TDM]) is therefore proposed for patients with unsatisfying response or tolerance ("rescue TDM"). A cycle of "routine TDM" for dosage individualization could also be beneficial to prevent unfavorable events, yet its clinical usefulness has not been evaluated. We aimed to assess prospectively whether a "routine TDM" intervention targeting imatinib Cmin of 1000 ng/mL (tolerance, 750-1500 ng/mL) could improve efficacy, tolerance, and persistence on treatment compared with "rescue TDM" use only. Patients (or Materials) and Methods: The Swiss Imatinib COncentration Monitoring Evaluation (I-COME) study was a multicenter randomized controlled trial (ISRCTN31181395). Adult patients in chronic or accelerated phase CML receiving imatinib ≤5 years were eligible. Patients were randomly (1:1) allocated to receive "routine TDM" intervention or to serve as controls with access only to "rescue TDM". All had 1-year follow-up. The primary endpoint was a combined efficacy-safety outcome (failure- and toxicity-free survival without imatinib discontinuation), analyzed in intention-to-treat. Results: Among 56 CML recruited patients, 55 had their molecular and cytogenetic response measured. 14/27 of patients receiving "routine TDM" (52% [33%-71%]) remained event-free versus 16/28 of control patients with "rescue TDM" only (57% [39%-75%]; P=0.69). In the "routine TDM" group, dosage recommendations were adopted entirely in 50% of patients (median Cmin at study end, 895 ng/mL; CV = 33%). These patients had fewer unfavorable events (28% [5%-52%]) compared with patients not receiving the advised dosage (77% [54%-99%]; P = 0.03; median Cmin at study end, 648 ng/mL; CV = 38%). Conclusion: This first prospective target concentration intervention trial could not formally demonstrate a benefit of "routine TDM" of imatinib, especially due to a small patient number and limited prescriber's adherence to dosage recommendations. Nevertheless, the patients receiving the advised dosage more often met target concentrations and the combined outcome (efficacy, tolerance, and persistence). A cycle of routine TDM could thus be favorable, at least in patients eligible for dosage adjustment. Its usefulness should, however, be further confirmed in larger trials.

Anaerobically controlled expression system derived from the arcDABC operon of Pseudomonas aeruginosa: application to lipase production.

The anaerobically inducible arcDABC operon encodes the enzymes of the arginine deiminase pathway in Pseudomonas aeruginosa. Upon induction, the arcAB mRNAs and proteins reach high intracellular levels, because of a strong anaerobically controlled promoter and mRNA processing in arcD, leading to stable downstream transcripts. We explored the usefulness of this system for the construction of expression vectors. The lacZ gene of Escherichia coli was expressed to the highest levels when fused close to the arc promoter. Insertion of lacZ further downstream into arcA or arcB did not stabilize the intrinsically unstable lacZ mRNA. On the contrary, lacZ mRNA appeared to be a vulnerable endonuclease target destabilizing arcAB mRNAs in the 5'-to-3' direction in P. aeruginosa. The native arc promoter was modified for optional expression in the -10 sequence and in the -40 region, which is a binding site for the anaerobic regulator ANR. In P. aeruginosa grown either anaerobically or with oxygen limitation in unshaken cultures, this promoter was stronger than the induced tac promoter. The P. aeruginosa lipAH genes, which encode extracellular lipase and lipase foldase, respectively, were fused directly to the modified arc promoter in an IncQ vector plasmid. Semianaerobic static cultures of P. aeruginosa PAO1 carrying this recombinant plasmid overproduced extracellular lipase 30-fold during stationary phase compared with the production by strain PAO1 without the plasmid. Severe oxygen limitation, in contrast, resulted in poor lipase productivity despite effective induction of the ANR-dependent promoter, suggesting that secretion of active lipase is blocked by the absence of oxygen. In conclusion, the modified arc promoter is useful for driving the expression of cloned genes in P. aeruginosa during oxygen-limited growth and stationary phase.

A nucleosome-dependent static loop potentiates estrogen-regulated transcription from the Xenopus vitellogenin B1 promoter in vitro.

We describe the transcriptional potentiation in estrogen responsive transcription extracts of the Xenopus vitellogenin B1 gene promoter through the formation of a positioned nucleosome. Nuclease digestion and hydroxyl radical cleavage indicate that strong, DNA sequence-directed positioning of a nucleosome occurs between -300 and -140 relative to the start site of transcription. Deletion of this DNA sequence abolishes the potentiation of transcription due to nucleosome assembly. The wrapping of DNA around the histone core of the nucleosome positioned between -300 and -140 creates a static loop in which distal estrogen receptor binding sites are brought close to proximal promoter elements. This might facilitate interactions between the trans-acting factors themselves and/or RNA polymerase. Such a nucleosome provides an example of how chromatin structure might have a positive effect on the transcription process.

Crystallization and preliminary X-ray analysis of monalysin, a novel β-pore-forming toxin from the entomopathogen Pseudomonas entomophila.

Monalysin was recently described as a novel pore-forming toxin (PFT) secreted by the Drosophila pathogen Pseudomonas entomophila. Recombinant monalysin is multimeric in solution, whereas PFTs are supposed to be monomeric until target membrane association. Monalysin crystals were obtained by the hanging-drop vapour-diffusion method using PEG 8000 as precipitant. Preliminary X-ray diffraction analysis revealed that monalysin crystals belonged to the monoclinic space group C2, with unit-cell parameters a = 162.4, b = 146.2, c = 144.4 Å, β = 122.8°, and diffracted to 2.85 Å resolution using synchrotron radiation. Patterson self-rotation analysis and Matthews coefficient calculation indicate that the asymmetric unit contains nine copies of monalysin. Heavy-atom derivative data were collected and a Ta6Br14 cluster derivative data set confirmed the presence of ninefold noncrystallographic symmetry.

Structural determinants involved in the activation and regulation of G protein-coupled receptors: lessons from the alpha1-adrenegic receptor subtypes.

The aim of a large number of studies on G protein-coupled receptors was centered on understanding the structural basis of their main functional properties. Here, we will briefly review the results obtained on the alpha1-adrenergic receptor subtypes belonging to the rhodopsin-like family of receptors. These findings contribute, on the one hand, to further understand the molecular basis of adrenergic transmission and, on the other, to provide some generalities on the structure-functional relationship of G protein-coupled receptors.