Langerin+ Dermal DC, but not Langerhans cells, are required for effective CD8 mediated immune responses after skin scarification with Vaccinia Virus (VACV)

Skin scarification (s.s.) with Vaccinia virus (VACV) is essential for generation of an optimal protective T cell memory immune response. Dendritic Cells (DC), which are professional antigen presenting cells, are required for naïve T cell priming and activation. At least three subsets of skin resident DC have been identified: Langerhans Cells (LC), Dermal Langerin+ DC (Lang+dDC) and Dermal Langerin− DC (Lang−dDC). Using Langerin-diphtheria toxin receptor mice and established mouse model of VACV delivered by s.s., we demonstrated that Lang+dDC, but not LC, are absolutely required for the induction of a rapid and robust antigen-specific CD8+ T cell response after s.s. with VACV. The depletion of Lang+dDC led to a significant delay in the priming and proliferation of antigen-specific CD8+ T cells. Moreover CD8+ T cells generated after VACV s.s. in the absence of Lang+dDC lacked effector cytotoxic functions both in vitro and in vivo. While s.s.-immunized WT and LC depleted mice controlled the progression of OVA257–264 expressing T cell lymphoma EG7 (injected intradermally), the depletion of Lang+dDC led to rapid lymphoma progression and mortality. These data indicate that of all skin DC subsets, Lang+dDC the most critical for the generation of robust CD8+ T cell immunity after s.s. with VACV

Keratinocyte Membrane-Associated Epidermal Cell-Derived Thymocyte-Activating Factor (ETAF)

This study describes the association between secreted keratinocyte interleukin 1 (IL-1) and its presence on the keratinocyte cell surface. These properties were studied in normal and transformed human keratinocytes as well as in transformed murine keratinocytes. we will present evidence that the secretion of IL-1 by human and murine keratinocytes is associated with the presence of IL-1 on the keratinocyte membrane. In addition, although transformed murine keratinocytes secrete other cytokines, namely keratinocyte T-cell growth factor (KTGF) and IL-3, no KTGF or IL-3 activity can be demonstrated on the cell surface

Situation selection and modification in social inhibition:A person-centered approach

Objectives The current study aimed to identify patterns of situation selection and modification behaviors using a person-centered approach, and to examine to what extent the trait social inhibition (SI) is associated with these patterns of situation-targeted emotion regulation. Methods The sample comprised 504 participants (Mage = 21.5, SD = 8.2; 82% women), who completed questionnaires on situation selection and modification behaviors, and the social inhibition questionnaire (SIQ15). A three-step latent profile analysis (LPA) was performed to (A) identify existing latent profiles of situation avoidance and approach and situation modification behaviors, and (B) to examine the association of SI and facets with the latent class posteriors. Results LPA revealed the presence of four profiles that differed in how situation selection and modification were applied. SI, behavioral inhibition, and social withdrawal were significantly associated with a higher odds of belonging to the profile characterized by avoidance selection and modification. Interpersonal sensitivity was associated with using more conversational modification behaviors, which may illustrate that interpersonal sensitive individuals are motivated to approach, but use avoidance behaviors to prevent confrontation. Conclusions SI individuals particularly rely on avoidance selection and modification behaviors, which may be considered maladaptive emotion regulation

Composition of LHB Comets and Their Influence on the Early Earth Atmosphere Composition

Two main processes were responsible for the composition of this atmosphere: chemical evolution of the volatile fraction of the accretion material forming the planet and the delivery of gasses to the planetary surface by impactors during the late heavy bombardment (LHB). The amount and composition of the volatile fraction influences the outgassing of the Earth mantle during the last planetary formation period. A very weakened form of outgassing activity can still be observed today by examining the composition of volcanic gasses. An enlightenment of the second process is based on the sparse records of the LHB impactors resulting from the composition of meteorites, observed cometary comas, and the impact material found on the Moon. However, for an assessment of the influence of the outgassing on the one hand and the LHB event on the other, one has to supplement the observations with numerical simulations of the formation of volatiles and their incorporation into the accretion material which is the precursors of planetary matter, comets and asteroids. These simulations are performed with a combined hydrodynamic-chemical model of the solar nebula (SN). We calculate the chemical composition of the gas and dust phase of the SN. From these data, we draw conclusions on the upper limits of the water content and the amount of carbon and nitrogen rich volatiles incorporated later into the accretion material. Knowing these limits we determine the portion of major gas compounds delivered during the LHB and compare it with the related quantities of the outgassed species

Bifurcations and stability of gap solitons in periodic potentials

We analyze the existence, stability, and internal modes of gap solitons in nonlinear periodic systems described by the nonlinear Schrodinger equation with a sinusoidal potential, such as photonic crystals, waveguide arrays, optically-induced photonic lattices, and Bose-Einstein condensates loaded onto an optical lattice. We study bifurcations of gap solitons from the band edges of the Floquet-Bloch spectrum, and show that gap solitons can appear near all lower or upper band edges of the spectrum, for focusing or defocusing nonlinearity, respectively. We show that, in general, two types of gap solitons can bifurcate from each band edge, and one of those two is always unstable. A gap soliton corresponding to a given band edge is shown to possess a number of internal modes that bifurcate from all band edges of the same polarity. We demonstrate that stability of gap solitons is determined by location of the internal modes with respect to the spectral bands of the inverted spectrum and, when they overlap, complex eigenvalues give rise to oscillatory instabilities of gap solitons.Comment: 18 pages, 11 figures; updated bibliograph

Counter-Regulation of Interleukin-1α (IL-1α) and IL-1 Receptor Antagonist in Murine Keratinocytes

Interleukin-1α (IL-1α) is a potent proinflammatory cytokine constitutively expressed by keratinocytes, which also synthesize a specific inhibitor of IL-1 activity, intracellular IL-1 receptor antagonist (IL-1ra). Although homeostatic regulation of the IL-1 system in keratinocytes has long been suspected, there is currently little evidence for this. To explore this issue, the PAM212 murine keratinocyte cell line was exposed to increasing concentrations of either IL-1α or IL-1ra and the opposing ligand was assessed by ELISA. Release of IL-1ra was induced following stimulation by murine IL-1α in a concentration-dependent manner and, conversely, IL-1ra stimulation increased IL-1α release. To determine whether a similar homeostatic circuit operates in vivo, epidermis from transgenic mice in which overexpression of IL-1α or IL-1ra was targeted to keratinocytes was analyzed. Epidermal sheets derived from IL-1α transgenic mice released eight times more IL-1ra than those from wild-type mice following ex vivo culture and similarly, IL-1α release was increased 3–4-fold in epidermal sheets derived from IL-1ra transgenic epidermis, Use of specific neutralizing antibodies against type I and type II IL-1 receptors indicated that the counter-regulation mechanism is mediated extracellularly through the type I IL-1 receptor alone. Taken together, these observations provide the first demonstration of mutual counter-regulation of IL-1 receptor ligands in keratinocytes

Validity of a multidimensional comprehensive psychosocial screening instrument based on the ESC cardiovascular prevention guidelines:Evidence from the general and cardiovascular patient population

Aim To evaluate the psychometric properties and validity of the updated version of the Dutch multidimensional Comprehensive Psychosocial Screening Instrument in patients with coronary heart disease and the general population, based upon guideline recommendations from the European Society for Cardiology. Method 678 participants (Mage = 48.2, SD = 16.8; 46% male) of the Dutch general population and 312 cardiac patients (Mage = 65.9, SD = 9.9; 77% male) who recently received percutaneous coronary intervention completed the Comprehensive Psychosocial Screening Instrument and validated questionnaires for depression (PHQ-9), anxiety (GAD-7), Type D personality (DS14), hostility (CMHS), anger (STAS-T), trauma (SRIP), and chronic work and family stress (ERI, MMQ-6). Results Confirmatory factor analysis (CFA) confirmed that the eight screened risk factors were best measured as separate entities, rather than broader indications of distress. Inter-instrument agreement, assessed with the intraclass coefficient (ICC) and the screening accuracy indicators (receiving operator characteristic [ROC] curves, sensitivity, specificity, and the positive and negative predictive values [PPV; NPV]) were good for most screened risk factors. PPV was low in low prevalence risk factors like anxiety, trauma, and depression. Conclusion Overall, the current version of the Comprehensive Psychosocial Screening Instrument has an acceptable performance in both populations, with a fair to excellent level of agreement with established full questionnaires. Besides a few suggestions for further refinement, the screener may be implemented in primary care and cardiological practice