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Background: Atopic dermatitis (AD) and allergic contact dermatitis (ACD) are both forms of eczema and are common inflammatory skin diseases with a central role of T cell-derived IL-22 in their pathogenesis. Although prostaglandin (PG) E-2 is known to promote inflammation, little is known about its role in processes related to AD and ACD development, including IL-22 upregulation. Objectives: We sought to investigate whether PGE(2) has a role in IL-22 induction and development of ACD, which has increased prevalence in patients with AD. Methods: T-cell cultures and in vivo sensitization of mice with haptens were used to assess the role of PGE(2) in IL-22 production. The involvement of PGE(2) receptors and their downstream signals was also examined. The effects of PGE(2) were evaluated by using the oxazolone-induced ACD mouse model. The relationship of PGE(2) and IL-22 signaling pathways in skin inflammation were also investigated by using genomic profiling in human lesional AD skin. Results: PGE(2) induces IL-22 from T cells through its receptors, E prostanoid receptor (EP) 2 and EP4, and involves cyclic AMP signaling. Selective deletion of EP4 in T cells prevents hapten-induced IL-22 production in vivo, and limits atopic-like skin inflammation in the oxazolone-induced ACD model. Moreover, both PGE(2) and IL-22 pathway genes were coordinately upregulated in human AD lesional skin but were at less than significant detection levels after corticosteroid or UVB treatments. Conclusions: Our results define a crucial role for PGE(2) in promoting ACD by facilitating IL-22 production from T cells.

Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy(1), this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry. We call this approach for the labelling of 'kiss-and-run' interactions between immune cells 'Labelling Immune Partnerships by SorTagging Intercellular Contacts' (LIPSTIC). Using LIPSTIC, we show that interactions between dendritic cells and CD4(+) T cells during T-cell priming in vivo occur in two distinct modalities: an early, cognate stage, during which CD40-CD40L interactions occur specifically between T cells and antigen-loaded dendritic cells; and a later, non-cognate stage during which these interactions no longer require prior engagement of the T-cell receptor. Therefore, LIPSTIC enables the direct measurement of dynamic cell-cell interactions both in vitro and in vivo. Given its flexibility for use with different receptor-ligand pairs and a range of detectable labels, we expect that this approach will be of use to any field of biology requiring quantification of intercellular communication.

Psoriasis vulgaris is a common, inflammatory skin disease affecting approximately 3% of the population in the United States. The etiology of psoriasis and its associated comorbidities are complex and the result of complicated interactions between the skin, immune system, disease-associated susceptibility loci, and multiple environmental triggers. The modeling of human disease in vivo through the use of murine models represents a powerful, indispensable tool for investigating the immune and genetic mechanisms contributing to a clinical disease phenotype. Nevertheless, modeling a complex, multigenic disease like psoriasis in mice has proven to be extremely challenging and is associated with significant limitations. Over the last four decades, more than 40 unique mouse models for psoriasis have been described. These models can be categorized into three major types: acute (inducible), genetically engineered (transgenic), and xenograft (humanized). The purpose of this Research Techniques Made Simple article is to provide an overview of the common types of psoriasis-like mouse models currently in use and their inherent advantages and limitations. We also highlight the need for improved psoriasis mouse model systems and several key factors to be considered as this field of laboratory science advances.

The cross sections for the production of t (t) over bar b (b) over bar and t (t) over bar jj events and their ratio sigma(t (t) over bar b (b) over bar)/sigma(t (t) over bar jj) are measured using data corresponding to an integrated luminosity of 2.3 fb(-1) collected in pp collisions at root s = 13 TeV with the CMS detector at the LHC. Events with two leptons (e or mu) and at least four reconstructed jets, including at least two identified as b quark jets, in the final state are selected. In the full phase space, the measured ratio is 0.022 +/- 0.003 (stat) +/- 0.006 (syst), the cross section sigma(t (t) over bar b (b) over bar) bis 4.0 +/- 0.6 (stat)+/- 1.3 (syst) pb and sigma(t (t) over bar jj) is 184 +/- 6 (stat)+/- 33 (syst) pb. The measurements are compared with the standard model expectations obtained from a POWHEG simulation at next-to-leading-order interfaced with PYTHIA. (c) 2017 The Author. Published by Elsevier B.V.

Background and Aims: The aim of this study was to evaluate the feasibility and early safety of catheter-directed irreversible electroporation (IRE) of the normal common bile duct (CBD) in swine. Methods: IRE (2000 V, 90 pulses, 100 mu s pulse) was performed in the CBD of 6 Yorkshire pigs using a catheter electrode under endoscopic guidance. Ductal patency was assessed with immediate retrograde cholangiography and contrast-enhanced CT imaging at 1 or 7 days after treatment. Animals were killed at either 1 day (n = 4, 2 ablations/animal) or 7 days (n = 2, 1 ablation/animal) after treatment. The biliary tract was extracted en bloc and the length of the ablation along the CBD mucosa was measured. The depth of ablation was quantified using cross-sections of the treated CBD wall stained with hematoxylin and eosin. Single-sample hypothesis testing was performed to verify whether the depth of ablation in the CBD was a representative outcome of IRE treatment. Results: IRE of the CBD did not result in perforation or obstruction of the organ at 1 or 7 days after treatment. The length of ablation along the CBD mucosa was 17.27 +/- 5.55 mm on day 1 samples, and transmural ablation of the CBD wall was a representative outcome of the treatment (7/8 samples, P < .05). Day 1 samples demonstrated loss of epithelium, transmural necrosis, with preservation of lumen integrity. Day 7 samples demonstrated reepithelialization, with diffuse transmural fibrosis of the CBD wall. These findings were absent from sham tissue samples. Conclusions: Intraluminal catheter-directed IRE is feasible and safe for full-thickness ablation of the normal porcine CBD without affecting lumen patency up to 1 week after treatment.

Apolipoprotein CI (ApoCI) belongs to the Apolipoprotein superfamily, members of which are involved in lipid transport, uptake and homeostasis. Excessive ApoCI has been implicated in atherosclerosis and Alzheimer's disease in humans. In this study we report the isolation of Xenopus laevis apoCI and describe the expression pattern of this gene during early development, using reverse transcription polymerase chain reaction and whole mount in situ hybridization. Xenopus apoCI is enriched in the dorsal ectoderm during gastrulation, and is subsequently expressed in sensory placodes, neural tube and cranial neural crest. These data suggest as yet uncharacterized roles for ApoCI during early vertebrate embryogenesis.

Stem cells of the small and large intestine are marked by expression of the Wnt target gene LGR5, a leucine-rich-repeat-containing G protein-coupled receptor. Previous studies reported increased expression of LGR5 in human colorectal cancer (CRC) compared to normal tissue either by immunohistochemistry or in situ hybridization (ISH). However, as these studies were semi-quantitative they did not provide a numerical estimate of the magnitude of this effect. While we confirm that LGR5(+) cells are exclusively located at the base of normal human small and large intestinal crypts, representing approximately 6% of total crypt cells, we show this cell population is 10-fold expanded in all grades of CRC, representing as much as 70% of the cells of tumor crypt-like structures. This expansion of the LGR5 compartment coincides with maintenance of crypt-like glandular structure (adenomas, and well and moderately differentiated adenocarcinomas), and is reduced in poorly differentiated CRC, where crypt-like glandular architecture is lost, accompanied by reduced epithelial terminal differentiation. Altogether these results indicate that LGR5(+) cell expansion is a hallmark of CRC tumorigenesis occurring during progression to adenoma, supporting CRC as a stem cell disease with implications for CRC therapy.

Cancer immunotherapy represents a promising treatment approach for malignant gliomas but is hampered by the limited number of ubiquitously expressed tumor antigens and the profoundly immunosuppressive tumor microenvironment. We identified cluster of differentiation (CD)70 as a novel immunosuppressive ligand and glioma target. Normal tissues derived from 52 different organs and primary and recurrent low-grade gliomas (LGGs) and glioblastomas (GBMs) were thoroughly evaluated for CD70 gene and protein expression. The association between CD70 and patients' overall survival and its impact on T-cell death was also evaluated. Human and mouse CD70-specific chimeric antigen receptors (CARs) were tested respectively against human primary GBMs and murine glioma lines. The antitumor efficacies of these CARs were also examined in orthotopic xenograft and syngeneic models. CD70 was not detected in peripheral and brain normal tissues but was constitutively overexpressed by isocitrate dehydrogenase (IDH) wild-type primary LGGs and GBMs in the mesenchymal subgroup and recurrent tumors. CD70 was also associated with poor survival in these subgroups, which may link to its direct involvement in glioma chemokine productions and selective induction of CD8+ T-cell death. To explore the potential for therapeutic targeting of this newly identified immunosuppressive axis in GBM tumors, we demonstrate that both human and mouse CD70-specific CAR T cells recognize primary CD70+ GBM tumors in vitro and mediate the regression of established GBM in xenograft and syngeneic models without illicit effect. These studies identify a previously uncharacterized and ubiquitously expressed immunosuppressive ligand CD70 in GBMs that also holds potential for serving as a novel CAR target for cancer immunotherapy in gliomas.

Although the surge in research into the neuroscience of resilience is relatively new, it has been able to elucidate the brain structures that underlie resilience and identify strategies for supporting brain health and mental health across the lifespan. Despite advances, neuroscientists need the input of social work clinicians and clinical researchers to continue to move the field forward. This article provides a narrative review of the recent literature on the neuroscience of resilience with the goal of informing social workers and social work researchers about the state of knowledge in this field. We restricted our review to research in the past 20 years on resilience to stress and trauma, including only those papers that relate to neuroscience or mental functioning. We summarize recent developments in the neuroscience of resiliencenotably the neural circuitry and physiology that underlie resilience in humans and animals. We go on to identify a number of interventions likely to promote resilience and resilient brain function, including parenting and community-based interventions for children and adolescents, hardiness training, meditation and mindfulness approaches, and aerobic exercise. Recommendations are made for future cross-disciplinary work.