T helper (Th) 17 cells have recently been implicated in psoriasis pathogenesis, but mechanisms of how these cells traffic into inflamed skin are unknown. By immunostaining for interleukin (IL)-17A and IL-22, we show numerous cells present in psoriasis lesions that produce these cytokines. We next found that Th17 cytokines (IL-17A, IL-22, and tumor necrosis factor (TNF)-α) markedly increased the expression of CC chemokine ligand (CCL) 20, a CC chemokine receptor (CCR)6 ligand, in human keratinocyte monolayer and raft cultures in a dose- and time-dependent manner. Lastly, we showed in mice that subcutaneous injection with recombinant IL-17A, IL-22, or TNF-α led to the upregulation of both CCL20 and CCR6 expression in skin as well as cutaneous T-cell infiltration. Taken together, these data show that Th17 cytokines stimulate CCL20 production in vitro and in vivo, and thus provide a potential explanation of how CCR6-positive Th17 cells maintain their continual presence in psoriasis through a positive chemotactic feedback loop.

Modern computational brain morphology methods require that anatomical images be acquired at high resolution and with a high signal-to-noise ratio. This often translates into long acquisition times (>20 minutes) and images susceptible to head motion. In this study we tested retrospective motion correction (RMC), common for functional MRI (fMRI) and PET image motion correction, as a means to improve the quality of high-resolution 3-D anatomical MR images. RMC methods are known to be effective for correcting interscan motion; therefore, a single high-resolution 3-D MRI brain study was divided into six shorter acquisition segments to help shift intrascan motion into interscan motion. To help reduce intrascan head motion, each segment image was reviewed for motion artifacts and repeated if necessary. Interscan motion correction was done by spatially registering images to the third image and forming a single average motion-corrected image. RMC was tested on 35 subjects who were considered at high risk for head motion. Our results show that RMC provided better contrast-to-noise ratio and boundary detail when compared to nonmotion-corrected averaged images.

The trimeric RNA polymerase complex (3P, for PA-PB1-PB2) of influenza A virus (IAV) is an important viral determinant of pathogenicity and host range restriction. Specific interactions of the polymerase complex with host proteins may be determining factors in both of these characteristics and play important roles in the viral life cycle. To investigate this question, we performed a comprehensive proteomic analysis of human host proteins associated with the polymerase of the well-characterized H5N1 Vietnam/1203/04 isolate. We identified over 400 proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS), of which over 300 were found to bind to the PA subunit alone. The most intriguing and novel finding was the large number of mitochondrial proteins (ϳ20%) that associated with the PA subunit. These proteins mediate molecular transport across the mitochondrial membrane or regulate membrane potential and may in concert with the identified mitochondrion-associated apoptosis inducing factor (AIFM1) have roles in the induction of apoptosis upon association with PA. Additionally, we identified host factors that associated with the PA-PB1 (68 proteins) and/or the 3P complex (34 proteins) including proteins that have roles in innate antiviral signaling (e.g., ZAPS or HaxI) or are cellular RNA polymerase accessory factors (e.g., polymerase I transcript release factor [PTRF] or Supt5H). IAV strain-specific host factor binding to the polymerase was not observed in our analysis. Overall, this study has shed light into the complex contributions of the IAV polymerase to host cell pathogenicity and allows for direct investigations into the biological significance of these newly described interactions.The trimeric RNA (3P) influenza virus polymerase complex (PA-PB1-PB2) assembles in the nucleus, where influenza virus replication occurs. Several events inside the host cell must take place in order to support viral replication, such as the regulation of early antiviral host responses, host protein shutoff, and nuclear transport of viral RNA and proteins (21,29,63). These events require the viral RNA polymerase to interact with cellular factors, some of which may also be important for host range specificity but have yet to be identified (17,44). A range of RNA interference (RNAi)-based, genome-wide screens have been published recently that identified host factors involved in influenza virus replication (4,22,31,35,52,56). Although the degree of overlap between these studies was minimal, similar biological pathways and functional classifications were identified, suggesting their importance in the influenza virus infectious cycle. Watanabe et al. (67) compiled a list of 128 proteins that affected influenza virus replication in at least two out of the six screens. These included proteins involved in the nuclear import of viral ribonucleoproteins (vRNPs), such as importin family members and nuclear pore complex proteins.Other studies have attempted to directly identify proteins that interact with either the influenza virus po...

CFD results from computational models of a DeBakey type III AD representing separate coverage of entrance and exit tears correlated with clinical experience. The reported results present a preliminary look at a complex clinical problem.

Fas ligand (FasL) causes apoptosis of epidermal keratinocytes and triggers the appearance of spongiosis in eczematous dermatitis. We demonstrate here that FasL also aggravates inflammation by triggering the expression of proinflammatory cytokines, chemokines, and adhesion molecules in keratinocytes. In HaCaT cells and in reconstructed human epidermis (RHE), FasL triggered a NF-kappaB-dependent mRNA accumulation of inflammatory cytokines (tumor necrosis factor-alpha, IL-6, and IL-1beta), chemokines (CCL2/MCP-1, CXCL1/GROalpha, CXCL3/GROgamma, and CXCL8/IL-8), and the adhesion molecule ICAM-1. Oligomerization of Fas was required both for apoptosis and for gene expression. Inhibition of caspase activity abolished FasL-dependent apoptosis; however, it failed to suppress the expression of FasL-induced genes. Additionally, in the presence of caspase inhibitors, but not in their absence, FasL triggered the accumulation of CCL5/RANTES (regulated on activation normal T cell expressed and secreted) mRNA. Our findings identify a novel proinflammatory role of FasL in keratinocytes that is independent of caspase activity and is separable from apoptosis. Thus, in addition to causing spongiosis, FasL may play a direct role in triggering and/or sustaining inflammation in eczemas.