Little is known about similarities and differences in voice hearing in schizophrenia and dissociative identity disorder (DID) and the role of child maltreatment and dissociation. This study examined various aspects of voice hearing, along with childhood maltreatment and pathological dissociation in 3 samples: schizophrenia without child maltreatment (n = 18), schizophrenia with child maltreatment (n = 16), and DID (n = 29). Compared with the schizophrenia groups, the DID sample was more likely to have voices starting before 18, hear more than 2 voices, have both child and adult voices and experience tactile and visual hallucinations. The 3 groups were similar in that voice content was incongruent with mood and the location was more likely internal than external. Pathological dissociation predicted several aspects of voice hearing and appears an important variable in voice hearing, at least where maltreatment is present.

By dampening DUBA expression, IL-1 receptor signals facilitate TLR9-driven TRAF3 ubiquitination, antiinflammatory cytokine production, and resistance to DSS-induced colitis.

Objective During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the joint extracellular matrix. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to RA FLS anomalous behavior. The receptor protein tyrosine phosphatase α (RPTPα), encoded by the PTPRA gene, is a key promoter of FAK signaling. Here we investigated whether RPTPα mediates FLS aggressiveness and RA pathogenesis. Methods Through RPTPα knockdown, we assessed FLS gene expression by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, invasion and migration in transwell assays, survival by Annexin V and propidium iodide staining, adhesion and spreading by immunofluorescence microscopy, and activation of signaling pathways by Western blotting of FLS lysates. Arthritis development was examined in Ptpra−/− mice using the K/BxN serum transfer model. The contribution of radiosensitive and radioresistant cells to disease was evaluated by reciprocal bone-marrow transplantation. Results RPTPα was enriched in the RA synovial lining. RPTPα knockdown impaired RA FLS survival, spreading, migration, invasiveness and responsiveness to platelet-derived growth factor, tumor necrosis factor and interleukin-1 stimulation. These phenotypes correlated with increased phosphorylation of SRC on inhibitory Y527 and decreased phosphorylation of FAK on stimulatory Y397. Treatment of RA FLS with an inhibitor of FAK phenocopied knockdown of RPTPα. Ptpra-deficient mice were protected from arthritis development, which was due to radioresistant cells. Conclusions By regulating phosphorylation of SRC and FAK, RPTPα mediates pro-inflammatory and pro-invasive signaling in RA FLS, correlating with promotion of disease in an FLS-dependent model of RA.

Background: We previously showed that immunization of mice with plasmid DNA (pDNA) encoding the Escherichia coli β-galactosidase gene (pCMV-LacZ) induces a Th1 response, whereas β-galactosidase (β-gal) in saline or alum induces a Th2 response. Furthermore, the Th1 response dominates over the Th2 response and downregulates preexisiting IgE antibody formation. Here, we determined by passive transfer of CD4+ or CD8+ lymphocytes and by immunizing β₂-microglobulin knockout (β₂-M KO) mice whether CD4+ and /or CD8+ cells from pDNA-immunized mice suppress IgE antibody production. Methods: BALB/c mice were injected with either CD4+ or CD8+ lymphocytes from naive β-gal-in-alum or pCMV-LacZ-immunized mice, then immunized with β-gal in alum, and the IgE antibody formation was determined. Second, C57BL/6 wild-type (WT) or β₂-M KO mice were immunized with β-gal or pCM V-LacZ, and the IgE antibody production was assessed. Results: Passive transfer of both CD4+ and CD8+ lymphocytes from pDNA-immunized mice suppressed the IgE antibody response by 90% compared to transfer of CD4+ T cells from naive or β-gal-in-alum immunized mice. β₂-M KO mice produced 3 times more IgE than the WT control mice both in the primary and secondary response. Conclusion: Both CD4+ and CD8+ subsets of T cells from pDNA-immunized mice can suppress IgE antibody production by affecting the primary response and/or by propagating the Thl memory response in a passive cell transfer system. Immunization with pDNA-encoding allergens may be an effective new form of immunotherapy for atopic diseases.

The innate immune system detects infection and tissue injury through different families of pattern-recognition receptors (PRRs), such as Toll-like receptors. Most PRR-mediated responses initiate elaborate processes of signaling, transcription, translation, and secretion of effector mediators, which together require time to achieve. Therefore, PRRmediated processes are not active in the early phases of infection. These considerations raise the question of how the host limits microbial replication and invasion during this critical period. Here, we examine the crucial defense mechanisms, such as antimicrobial peptides or extracellular traps, typically activated within minutes of the initial infection phase, which we term the "immediate protective response". Deficiencies in different components of the immediate protective response are often associated with severe and recurrent infectious diseases in humans, highlighting their physiologic importance. Keywords: Antimicrobial response r Infection r Innate immunity IntroductionInfection activates the innate immune response through different families of germline-encoded pattern-recognition receptors (PRRs), among which the Toll-like receptors (TLRs) are the most studied. These PRRs are expressed on the cell membranes or in the cytosol of immune and other cells and respond to microbial signature compounds, known as pathogen-associated molecular patterns (PAMPs). As a result, an acute inflammatory/defense response is initiated that is able to target a wide range of microbial agents and/or infected cells.Interestingly, tissue injury caused by sterile insults, such as trauma or hypoxia, activates a similar early inflammatory response. One potential evolutionary explanation for these similarities is that tissue injury usually results in the disruption of physiological barriers followed by microbial invasion. Another possibility is that microbes can also cause cell necrosis, so responding to tissue injury may be an indirect way of detecting microbial invasion. Thus, the mammalian host has developed a system Correspondence: Dr. José M. González-Navajas e-mail: gonzalez_josnav@gva.es of endogenous warning signals that are constitutively available and are rapidly activated in the very early phase of both sterile and nonsterile inflammation. These warning signals are provoked by alarmins or danger-associated molecular patterns. Alarmins are multifunctional endogenous molecules of structural heterogeneity, such as ATP, high-mobility group protein B1, or heat shock proteins, that are passively released following nonapoptotic cell death or actively secreted by leukocytes and epithelial cells [1]. As potent inducers of inflammatory responses, alarmins contribute to the defense against pathogens and promote tissue repair, but excessive alarmin secretion is also associated with acute and chronic inflammatory conditions [2].Stimulation of immune cells by endogenous alarmins or microbial derived PAMPs evokes similar signaling cascades and activates similar transcription factors [3] that c...