In vivo TCR Signaling in CD4(+) T Cells Imprints a Cell-Intrinsic, Transient Low-Motility Pattern Independent of Chemokine Receptor Expression Levels, or Microtubular Network, Integrin, and Protein Kinase C Activity

Intravital imaging has revealed that T cells change their migratory behavior during physiological activation inside lymphoid tissue. Yet, it remains less well investigated how the intrinsic migratory capacity of activated T cells is regulated by chemokine receptor levels or other regulatory elements. Here, we used an adjuvant-driven inflammation model to examine how motility patterns corresponded with CCR7, CXCR4, and CXCR5 expression levels on ovalbumin-specific DO11.10 CD4(+) T cells in draining lymph nodes. We found that while CCR7 and CXCR4 surface levels remained essentially unaltered during the first 48-72 h after activation of CD4(+) T cells, their in vitro chemokinetic and directed migratory capacity to the respective ligands, CCL19, CCL21, and CXCL12, was substantially reduced during this time window. Activated T cells recovered from this temporary decrease in motility on day 6 post immunization, coinciding with increased migration to the CXCR5 ligand CXCL13. The transiently impaired CD4(+) T cell motility pattern correlated with increased LFA-1 expression and augmented phosphorylation of the microtubule regulator Stathmin on day 3 post immunization, yet neither microtubule destabilization nor integrin blocking could reverse TCR-imprinted unresponsiveness. Furthermore, protein kinase C (PKC) inhibition did not restore chemotactic activity, ruling out PKC-mediated receptor desensitization as mechanism for reduced migration in activated T cells. Thus, we identify a cell-intrinsic, chemokine receptor level-uncoupled decrease in motility in CD4(+) T cells shortly after activation, coinciding with clonal expansion. The transiently reduced ability to react to chemokinetic and chemotactic stimuli may contribute to the sequestering of activated CD4(+) T cells in reactive peripheral lymph nodes, allowing for integration of costimulatory signals required for full activation.

CD4+ T cell help improves CD8+ T cell memory by retained CD27 expression

CD4+ T cell help during the priming of CD8+ T lymphocytes imprints the capacity for optimal secondary expansion upon re-encounter with antigen. Helped memory CD8+ T cells rapidly expand in response to a secondary antigen exposure, even in the absence of T cell help and, are most efficient in protection against a re-infection. In contrast, helpless memory CTL can mediate effector function, but secondary expansion is reduced. How CD4+ T cells instruct CD8+ memory T cells during priming to undergo efficient secondary expansion has not been resolved in detail. Here, we show that memory CTL after infection with lymphocytic choriomeningitis virus are CD27(high) whereas memory CTL primed in the absence of CD4+ T cell have a reduced expression of CD27. Helpless memory CTL produced low amounts of IL-2 and did not efficiently expand after restimulation with peptide in vitro. Blocking experiments with monoclonal antibodies and the use of CD27(-/-) memory CTL revealed that CD27 ligation during restimulation increased autocrine IL-2 production and secondary expansion. Therefore, regulating CD27 expression on memory CTL is a novel mechanism how CD4+ T cells control CTL memory.

A new Bayesian approach to the reconstruction of spectral functions

We present a novel approach for the reconstruction of spectra from Euclidean correlator data that makes close contact to modern Bayesian concepts. It is based upon an axiomatically justified dimensionless prior distribution, which in the case of constant prior function m(ω) only imprints smoothness on the reconstructed spectrum. In addition we are able to analytically integrate out the only relevant overall hyper-parameter α in the prior, removing the necessity for Gaussian approximations found e.g. in the Maximum Entropy Method. Using a quasi-Newton minimizer and high-precision arithmetic, we are then able to find the unique global extremum of P[ρ|D] in the full Nω » Nτ dimensional search space. The method actually yields gradually improving reconstruction results if the quality of the supplied input data increases, without introducing artificial peak structures, often encountered in the MEM. To support these statements we present mock data analyses for the case of zero width delta peaks and more realistic scenarios, based on the perturbative Euclidean Wilson Loop as well as the Wilson Line correlator in Coulomb gauge.

EU agricultural reform fails on biodiversity

In December 2013, the European Union (EU) enacted the reformed Common Agricultural Policy (CAP) for 2014–2020, allocating almost 40% of the EU's budget and influencing management of half of its terrestrial area. Many EU politicians are announcing the new CAP as “greener,” but the new environmental prescriptions are so diluted that they are unlikely to benefit biodiversity. Individual Member States (MSs), however, can still use flexibility granted by the new CAP to design national plans to protect farmland habitats and species and to ensure long-term provision of ecosystem services

VIRTOPSY--scientific documentation, reconstruction and animation in forensic: individual and real 3D data based geo-metric approach including optical body/object surface and radiological CT/MRI scanning.

Until today, most of the documentation of forensic relevant medical findings is limited to traditional 2D photography, 2D conventional radiographs, sketches and verbal description. There are still some limitations of the classic documentation in forensic science especially if a 3D documentation is necessary. The goal of this paper is to demonstrate new 3D real data based geo-metric technology approaches. This paper present approaches to a 3D geo-metric documentation of injuries on the body surface and internal injuries in the living and deceased cases. Using modern imaging methods such as photogrammetry, optical surface and radiological CT/MRI scanning in combination it could be demonstrated that a real, full 3D data based individual documentation of the body surface and internal structures is possible in a non-invasive and non-destructive manner. Using the data merging/fusing and animation possibilities, it is possible to answer reconstructive questions of the dynamic development of patterned injuries (morphologic imprints) and to evaluate the possibility, that they are matchable or linkable to suspected injury-causing instruments. For the first time, to our knowledge, the method of optical and radiological 3D scanning was used to document the forensic relevant injuries of human body in combination with vehicle damages. By this complementary documentation approach, individual forensic real data based analysis and animation were possible linking body injuries to vehicle deformations or damages. These data allow conclusions to be drawn for automobile accident research, optimization of vehicle safety (pedestrian and passenger) and for further development of crash dummies. Real 3D data based documentation opens a new horizon for scientific reconstruction and animation by bringing added value and a real quality improvement in forensic science.