Tissue Specific Deletion of Inhibitor of Kappa B Kinase 2 with OX40-Cre Reveals the Unanticipated Expression from the OX40 Locus in Skin Epidermis

NF-κB signalling plays an essential role in T cell activation and generation of regulatory and memory populations in vivo. In the present study, we aimed to investigate the role of NF-κB signalling in post-activation T cells using tissue specific ablation of inhibitor of kappa-B kinase 2 expression, an important component of the inhibitor of kappa-B kinase complex in canonical NF-κB signalling. The OX40 antigen is expressed on activated T cells. Therefore, we used previously described mouse strain expressing Cre recombinase from the endogenous OX40 locus. Ablation of IKK2 expression using OX40Cre mice resulted in the development of an inflammatory response in the skin epidermis causing wide spread skin lesions. The inflammatory response was characterised by extensive leukocytic infiltrate in skin tissue, hyperplasia of draining lymph nodes and widespread activation in the T cell compartment. Surprisingly, disease development did not depend on T cells but was rather associated with an unanticipated expression of Cre in skin epidermis, and activation of the T cell compartment did not require Ikbk2 deletion in T cells. Employment of Cre reporter strains revealed extensive Cre activity in skin epidermis. Therefore, development of skin lesions was rather more likely explained by deletion of Ikbk2 in skin keratinocytes in OX40Cre mice

Structural diversity of supercoiled DNA

By regulating access to the genetic code, DNA supercoiling strongly affects DNA metabolism. Despite its importance, however, much about supercoiled DNA (positively supercoiled DNA, in particular) remains unknown. Here we use electron cryo-tomography together with biochemical analyses to investigate structures of individual purified DNA min icircle topoisomers with defined degrees of supercoiling. Our results reveal that each topoisomer, negative or positive, adopts a unique and surprisingly wide distribution of three-dimensional conformations. Moreover, we uncover striking differences in how the topoisomers handle torsional stress. As negative supercoiling increases, bases are increasingly exposed. Beyond a sharp supercoiling threshold, we also detect exposed bases in positively supercoiled DNA. Molecular dynamics simulations independently confirm the conformational heterogeneity and provide atomistic insight into the flexibility of supercoiled DNA. Our integrated approach reveals the three-dimensional structures of DNA that are essential for its function

Long-Range Autocorrelations of CpG Islands in the Human Genome

In this paper, we use a statistical estimator developed in astrophysics to study the distribution and organization of features of the human genome. Using the human reference sequence we quantify the global distribution of CpG islands (CGI) in each chromosome and demonstrate that the organization of the CGI across a chromosome is non-random, exhibits surprisingly long range correlations (10 Mb) and varies significantly among chromosomes. These correlations of CGI summarize functional properties of the genome that are not captured when considering variation in any particular separate (and local) feature. The demonstration of the proposed methods to quantify the organization of CGI in the human genome forms the basis of future studies. The most illuminating of these will assess the potential impact on phenotypic variation of inter-individual variation in the organization of the functional features of the genome within and among chromosomes, and among individuals for particular chromosomes

Humans integrate visual and haptic information in a statistically optimal fashion

Ernst MO, Banks MS. Humans integrate visual and haptic information in a statistically optimal fashion. Nature. 2002;415(6870):429-433.When a person looks at an object while exploring it with their hand, vision and touch both provide information for estimating the properties of the object. Vision frequently dominates the integrated visual-haptic percept, for example when judging size, shape or position(1-3), but in some circumstances the percept is clearly affected by haptics(4-7). Here we propose that a general principle, which minimizes variance in the final estimate, determines the degree to which vision or haptics dominates. This principle is realized by using maximum-likelihood estimation(8-15) to combine the inputs. To investigate cue combination quantitatively, we first measured the variances associated with visual and haptic estimation of height. We then used these measurements to construct a maximum-likelihood integrator. This model behaved very similarly to humans in a visual-haptic task. Thus, the nervous system seems to combine visual and haptic information in a fashion that is similar to a maximum-likelihood integrator. Visual dominance occurs when the variance associated with visual estimation is lower than that associated with haptic estimation

Within- and cross-modal distance information disambiguate visual size- perception

Perception is fundamentally underconstrained because different combinations of object properties can generate the same sensory information. To disambiguate sensory information into estimates of scene properties, our brains incorporate prior knowledge and additional “auxiliary” (i.e., not directly relevant to desired scene property) sensory information to constrain perceptual interpretations. For example, knowing the distance to an object helps in perceiving its size. The literature contains few demonstrations of the use of prior knowledge and auxiliary information in combined visual and haptic disambiguation and almost no examination of haptic disambiguation of vision beyond “bistable” stimuli. Previous studies have reported humans integrate multiple unambiguous sensations to perceive single, continuous object properties, like size or position. Here we test whether humans use visual and haptic information, individually and jointly, to disambiguate size from distance. We presented participants with a ball moving in depth with a changing diameter. Because no unambiguous distance information is available under monocular viewing, participants rely on prior assumptions about the ball's distance to disambiguate their -size percept. Presenting auxiliary binocular and/or haptic distance information augments participants' prior distance assumptions and improves their size judgment accuracy—though binocular cues were trusted more than haptic. Our results suggest both visual and haptic distance information disambiguate size perception, and we interpret these results in the context of probabilistic perceptual reasoning.Max Planck Society for the Advancement of ScienceUnited States. Office of Naval Research (N 00014-07-1-0937)SFB (550-A11)EU (grant 27141 ‘‘ImmerSence’’)University of Minnesota Doctoral Dissertation Fellowshi