Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.

NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.

European Union Eastern Enlargement - Expectations and Experiences of Doing Business in the New Member States

This publication deals with various aspects of European Union enlargement effects faced by the companies from EU15 and especially from Finland when doing business in the ten transitional economies which joined European Union in 2004 and 2007

Vanishing chromosomal inversion clines in Drosophila subobscura from Chile: Is behavioral thermoregulation to blame?

Chromosomal inversion clines paralleling the long-standing ones in native Palearctic populations of Drosophila subobscura evolved swiftly after this species invaded the Americas in the late 1970s and early 1980s. However, the new clines did not consistently continue to converge on the Old World baseline. Our recent survey of Chilean populations of D. subobscura shows that inversion clines have faded or even changed sign with latitude. Here, we investigate the hypothesis that this fading of inversion clines might be due to the Bogert effect, namely, that flies' thermoregulatory behavior has eventually compensated for environmental variation in temperature, thus buffering selection on thermal-related traits. We show that latitudinal divergence in thermal preference (T-p) has evolved in Chile for females, with higher-latitude flies having a lower mean T-p. Plastic responses in T-p also lessen latitudinal thermal variation because flies developed at colder temperatures prefer warmer microclimates. Our results are consistent with the idea that active behavioral thermoregulation might buffer environmental variation and reduce the potential effect of thermal selection on other traits as chromosomal arrangements.

The Impact of a Character Posture Model on the Communication of Affect in an Immersive Virtual Environment

This paper presents the quantitative and qualitative findings from an experiment designed to evaluate a developing model of affective postures for full-body virtual characters in immersive virtual environments (IVEs). Forty-nine participants were each requested to explore a virtual environment by asking two virtual characters for instructions. The participants used a CAVE-like system to explore the environment. Participant responses and their impression of the virtual characters were evaluated through a wide variety of both quantitative and qualitative methods. Combining a controlled experimental approach with various data-collection methods provided a number of advantages such as providing a reason to the quantitative results. The quantitative results indicate that posture plays an important role in the communication of affect by virtual characters. The qualitative findings indicated that participants attribute a variety of psychological states to the behavioral cues displayed by virtual characters. In addition, participants tended to interpret the social context portrayed by the virtual characters in a holistic manner. This suggests that one aspect of the virtual scene colors the perception of the whole social context portrayed by the virtual characters. We conclude by discussing the importance of designing holistically congruent virtual characters especially in immersive settings.

Being Small for Gestational Age: Does it Matter for the Neurodevelopment of Premature Infants? A Cohort Study.

BACKGROUND: Whether being small for gestational age (SGA) increases the risk of adverse neurodevelopmental outcome in premature infants remains controversial. OBJECTIVE: to study the impact of SGA (birthweight < percentile 10) on cognition, behavior, neurodevelopmental impairment and use of therapy at 5 years old. METHODS: This population-based prospective cohort included infants born before 32 weeks of gestation. Cognition was evaluated with the K-ABC, and behavior with the Strengths and Difficulties Questionnaire (SDQ). Primary outcomes were cognitive and behavioral scores, as well as neurodevelopmental impairment (cognitive score < 2SD, hearing loss, blindness, or cerebral palsy). The need of therapy, an indirect indicator of neurodevelopmental impairment, was a secondary outcome. Linear and logistic regression models were used to analyze the association of SGA with neurodevelopment. RESULTS: 342/515 (76%) premature infants were assessed. SGA was significantly associated with hyperactivity scores of the SDQ (coefficient 0.81, p < 0.04), but not with cognitive scores, neurodevelopmental impairment or the need of therapy. Gestational age, socio-economic status, and major brain lesions were associated with cognitive outcome in the univariate and multivariate model, whereas asphyxia, sepsis and bronchopulmonary dysplasia were associated in the univariate model only. Severe impairment was associated with fetal tobacco exposition, asphyxia, gestational age and major brain lesions. Different neonatal factors were associated with the use of single or multiple therapies: children with one therapy were more likely to have suffered birth asphyxia or necrotizing enterocolitis, whereas the need for several therapies was predicted by major brain lesions. DISCUSSION: In this large cohort of premature infants, assessed at 5 years old with a complete panel of tests, SGA was associated with hyperactive behavior, but not with cognition, neurodevelopmental impairment or use of therapy. Birthweight <10th percentile alone does not appear to be an independent risk factor of neurodevelopmental adverse outcome in preterm children.

Transcranial Magnetic Stimulation Combined with EEG Reveals Covert States of Elevated Excitability in the Human Epileptic Brain.

BACKGROUND: Transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) can be used to explore the dynamical state of neuronal networks. In patients with epilepsy, TMS can induce epileptiform discharges (EDs) with a stochastic occurrence despite constant stimulation parameters. This observation raises the possibility that the pre-stimulation period contains multiple covert states of brain excitability some of which are associated with the generation of EDs. OBJECTIVE: To investigate whether the interictal period contains "high excitability" states that upon brain stimulation produce EDs and can be differentiated from "low excitability" states producing normal appearing TMS-EEG responses. METHODS: In a cohort of 25 patients with Genetic Generalized Epilepsies (GGE) we identified two subjects characterized by the intermittent development of TMS-induced EDs. The high-excitability in the pre-stimulation period was assessed using multiple measures of univariate time series analysis. Measures providing optimal discrimination were identified by feature selection techniques. The "high excitability" states emerged in multiple loci (indicating diffuse cortical hyperexcitability) and were clearly differentiated on the basis of 14 measures from "low excitability" states (accuracy = 0.7). CONCLUSION: In GGE, the interictal period contains multiple, quasi-stable covert states of excitability a class of which is associated with the generation of TMS-induced EDs. The relevance of these findings to theoretical models of ictogenesis is discussed.

Functional importance of cardiac enhancer-associated noncoding RNAs in heart development and disease.

The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that fetal cardiac enhancers generate long noncoding RNAs (lncRNAs) during cardiac differentiation and morphogenesis. Enhancer expression correlates with the emergence of active enhancer chromatin states, the initiation of RNA polymerase II at enhancer loci and expression of target genes. Orthologous human sequences are also transcribed in fetal human hearts and cardiac progenitor cells. Through a systematic bioinformatic analysis, we identified and characterized, for the first time, a catalog of lncRNAs that are expressed during embryonic stem cell differentiation into cardiomyocytes and associated with active cardiac enhancer sequences. RNA-sequencing demonstrates that many of these transcripts are polyadenylated, multi-exonic long noncoding RNAs. Moreover, knockdown of two enhancer-associated lncRNAs resulted in the specific downregulation of their predicted target genes. Interestingly, the reactivation of the fetal gene program, a hallmark of the stress response in the adult heart, is accompanied by increased expression of fetal cardiac enhancer transcripts. Altogether, these findings demonstrate that the activity of cardiac enhancers and expression of their target genes are associated with the production of enhancer-derived lncRNAs.

Image Resilience after Multiple Crises : The Case of Switzerland in the United States

In der heutigen Welt sind die Reputation und das Image eines Landes als wichtige Faktoren für den wirtschaftlichen und politischen Erfolg angesehen. Jedoch ist die Pflege der Marke eines Landes komplex und führt zu zwei Positionen, die sich potentiell widersprechen: Einerseits kann ein positives Erscheinungsbild eines Landes durch aktive Massnahmen gefördert werden. Andererseits ist es schwierig, das Bild eines Landes abzugrenzen und es ist mit Klischees behaftet. Dieser Beitrag analysiert die Auswirkungen von zwei grösseren Krisen auf das Image der Schweiz in den Vereinigten Staaten: die Krise um die nachrichtenlosen Vermögen aus der Zeit des 2. Weltkriegs im Jahr 2000 sowie die Krise um die UBS und das Bankgeheimnis im Jahr 2009. Die Studie zeigt, dass das Erscheinungsbild der Schweiz unberührt blieb, obwohl ein beachtlicher Teil der Bevölkerung und der Meinungsführer von beiden Krisen wusste. Dies stützt die Hypothese, dass das Image eines Landes eine hohe Beständigkeit aufweist. In today's world, country's reputation and image have become key issues, widely believed to be success factors both economically and politically. Nevertheless, managing a country's brand is complex and leads to two positions that are potentially contradictory: On the one hand, a country's image can be influenced either by promotional activities. On the other hand, a country's image is a construct that is very difficult to delimit and is highly stereotyped. This contribution study the impact of two major crises on the image of Switzerland in the United States: the unclaimed wartime deposits crisis in 2000 and the UBS and banking secrecy crisis in 2009. It shows that despite the fact that a substantial proportion of the public and of opinion leaders was aware of both crises, the image of Switzerland was unaffected, which tends to support the hypothesis of strong stability of a country's image.