The meaning of marriage for men during the transition to fatherhood : the Swiss context

In Europe, Switzerland presents an unusual pattern of marriage with a very high proportion of couples who begin to cohabit without being married, but with a very low proportion of nonmarital births. A lot of couples marry before the conception of the child or during the pregnancy. In this article we focus on the point of view of men vis-agrave-vis the marriage and its meanings. Qualitative investigations show that men strongly desire marriage for several reasons, from their desire to participate in child rearing to the fear of having their paternity denied by Swiss institutions

Affective and physiological responses to environmental noises and music

Research suggests that respiratory patterns may reflect general dimensions of emotional response. In this study, we investigated the relationships between judgments of affective valence (pleasantness) and arousal and respiratory responses to acoustic stimuli. Sixteen environmental noises and 16 musical fragments of 30 s duration were presented to 31 participants, while respiration, skin conductance level and heart rate were recorded. Judgments of valence and arousal were registered using the 9-point Self-Assessment Manikin. For noises, breathing accelerated and minute ventilation augmented with decreases in pleasantness for low-arousal stimuli and with increases in arousal for positive stimuli. For music, breathing accelerated and minute ventilation augmented with increases both in rated valence and arousal. Skin conductance level increased with arousal ratings for music but not for noises, whereas mean heart rate increased with rated arousal for noises but not for music. Although both noises and music are sound-vibrations, differences in the relationships between affective judgments and physiological responses were found suggesting differences in the processing of the two types of acoustic stimuli. [Authors]

Music Performance Anxiety (MPA) : cardiorespiratory activity in high- and low-anxious professional music students before a performance situation

Descriptors: music performance anxiety, respiration, hyperventilation Surveys indicate that high-anxious musicians may suffer from hyperventilation (HV) before or during performance. Reported symptoms include shortness of breath, fast/ deep breathing and thumping heart. However, no study has yet tested if these selfreported symptoms reflect actual cardiorespiratory activity. Themain goal of this study was to determine if MPA is manifested physiologically in specific correlates of cardiorespiratory activity associated with HV.We studied 74 professional music students from Swiss Music Academies. In this study, we compared the most anxious students (highanxious; n 5 20) with the least anxious students (low-anxious; n 5 23) based on their self-reported performance anxiety. We measured cardiorespiratory patterns with the Lifeshirt system, end-tidal CO2 with a capnograph (EtCO2, a good non-invasive estimator of HV), self-perceived physiological activation and affective experience in three situations on different days: baseline, performance without audience, and performance with audience. Comparing measures for the private vs. the public concert, high- compared to low-anxious students showed a significant drop in EtCO2 before the public concert and reported larger increases in anxiety, tension, palpitations and breathing difficulties. In contrast, heart rate, respiratory rate and volume did not differ significantly between groups. The results of this study support the hypothesis thatMPA may be associated with a tendency to hyperventilate and, thus, point to a potential hyperventilation problem in high-anxious music students.

Molecular Analysis of the PTEN Gene in a Choroidal Schwannoma in the Context of a Hamartomatous Syndrome

Purpose: To investigate the molecular involvement of PTEN, a tumor suppressor gene, in a case of cellular pigmented choroidal Schwannoma in a patient with hamartomatous syndrome due to heterozygous PTEN germline mutation. Methods: Histopathological, immunohistochemical, and electron microscopy analyses were performed by standard procedures. Paraffin-embedded samples of normal and tumor eye tissues were collected and DNA was extracted. A 145 bp region flanking the heterozygous c.406T>C mutation in exon 5 of PTEN was amplified by PCR and sequenced. To evaluate the allelic status of PTEN in the tumor sample, we cloned different PCR products in E. coli using a TA cloning procedure. Results: Histopathology demonstrated a posterior choroidal mass measuring 1.3 x 1.6 x 1.4 cm. The tumor was composed by fascicles of spindle cells with wavy cytoplasm. No Verrocay bodies could be identified. Scattered histiocytes with clear cytoplasm were present. By immunohistochemistry, the cells were expressing S100 and focally Melan A proteins. Pericellular type IV collagen could be demonstrated. Interlacing cytoplasmic processes covered by thick basement membrane could be found by electron microscopy as well as few premelanosomes. Moderate PTEN expression by immunohistochemistry was identified in some cells. As expected, the germline mutation could be detected by DNA sequencing in both the paraffin-embedded normal and tumor eye tissues. Analysis of 33 E. coli colonies bearing clones from the tumor eye tissue DNA surprisingly revealed that most of them contained the PTEN wild-type allele (29 vs. 4, Fisher's test p-value = 0.002). Conclusions: This is the first reported case of choroidal cellular Schwannoma arising in the context of a PTEN hamartomatous syndrome. Allelic analysis of PTEN in the tumor suggests a statistically-significant partial loss of heterozygozity in favor of the wild-type allele. Our findings are in clear contrast with what is usually observed in cancer tissues, for which mutated alleles of tumor suppressor genes are usually brought to homozygosity. Similar results were previously reported in human non-Hodgkin's lymphomas, displaying an overexpression of the wild-type form of the tumor suppressor gene p53. We are in the process of investigating additional DNA derived from other fresh and paraffin-embedded tissues from the patient, in order to gain insights on the molecular bases of PTEN involvement in this rare choroidal Schwannoma.

Context specific affinity thresholds for CD8 T cell activation

After antigen driven activationnaïve CD8 T cells develop intocytolytic effector cells and subsequentlyinto memory cells. The molecularinteractions orchestrating Tcell activation are complex and we sofar have a limited understanding howindividual signals impact the Tcell response.Using OT-1 TCR transgeniccells and Listeria monocytogenesstrains expressing a set of altered peptideligands (APL) for the OT-1 TCRwe have recently studied how thelevel of TCR stimulation impacts theT cell response in vivo. We therebyobserved that even very low levels ofTCR stimulation are sufficient forfunctional effector and memoryT celldifferentiation. In order to addresshow much further the level of TCRstimulation can be reduced until the Tcells do not become activated anymore,we generated additional OT-1APL expressing Listeria strains. TheAPLused in our present study cover arange of potency down to the level ofpositive selection. Using all our APLListeria strains we can demonstratethat the threshold of peripheral T cellactivation is above the level of positiveselection but far below the levelthat is thought to be required for negativeselection. Furthermore, we characterizedthe thresholds of activatingmemory T cells and found them intrinsicallyto be very similar to thoseof naïve T cells. However, we observedthat T cell competition at thelevel of antigen presenting cells criticallyraises the activation threshold ofmemory CD8 T cells. Taken togetherour data indicate that the threshold foractivating T cells critically dependson the context and the environment inwhich T cells respond to antigen.

Context-dependent dual role of SKI8 homologs in mRNA synthesis and turnover.

Eukaryotic mRNA transcription and turnover is controlled by an enzymatic machinery that includes RNA polymerase II and the 3' to 5' exosome. The activity of these protein complexes is modulated by additional factors, such as the nuclear RNA polymerase II-associated factor 1 (Paf1c) and the cytoplasmic Superkiller (SKI) complex, respectively. Their components are conserved across uni- as well as multi-cellular organisms, including yeast, Arabidopsis, and humans. Among them, SKI8 displays multiple facets on top of its cytoplasmic role in the SKI complex. For instance, nuclear yeast ScSKI8 has an additional function in meiotic recombination, whereas nuclear human hSKI8 (unlike ScSKI8) associates with Paf1c. The Arabidopsis SKI8 homolog VERNALIZATION INDEPENDENT 3 (VIP3) has been found in Paf1c as well; however, whether it also has a role in the SKI complex remains obscure so far. We found that transgenic VIP3-GFP, which complements a novel vip3 mutant allele, localizes to both nucleus and cytoplasm. Consistently, biochemical analyses suggest that VIP3-GFP associates with the SKI complex. A role of VIP3 in the turnover of nuclear encoded mRNAs is supported by random-primed RNA sequencing of wild-type and vip3 seedlings, which indicates mRNA stabilization in vip3. Another SKI subunit homolog mutant, ski2, displays a dwarf phenotype similar to vip3. However, unlike vip3, it displays neither early flowering nor flower development phenotypes, suggesting that the latter reflect VIP3's role in Paf1c. Surprisingly then, transgenic ScSKI8 rescued all aspects of the vip3 phenotype, suggesting that the dual role of SKI8 depends on species-specific cellular context.

Hes1 is a critical but context-dependent mediator of canonical Notch signaling in lymphocyte development and transformation.

Although canonical Notch signaling regulates multiple hematopoietic lineage decisions including T cell and marginal zone B cell fate specification, the downstream molecular mediators of Notch function are largely unknown. We showed here that conditional inactivation of Hes1, a well-characterized Notch target gene, in adult murine bone marrow (BM) cells severely impaired T cell development without affecting other Notch-dependent hematopoietic lineages such as marginal zone B cells. Competitive mixed BM chimeras, intrathymic transfer experiments, and in vitro culture of BM progenitors on Delta-like-expressing stromal cells further demonstrated that Hes1 is required for T cell lineage commitment, but dispensable for Notch-dependent thymocyte maturation through and beyond the beta selection checkpoint. Furthermore, our data strongly suggest that Hes1 is essential for the development and maintenance of Notch-induced T cell acute lymphoblastic leukemia. Collectively, our studies identify Hes1 as a critical but context-dependent mediator of canonical Notch signaling in the hematopoietic system.