TRANCE, a tumor necrosis factor family member critical for CD40 ligand- independent T helper cell activation

CD40 ligand (CD40L), a tumor necrosis factor (TNF) family member, plays a critical role in antigen-specific T cell responses in vivo. CD40L expressed on activated CD4+ T cells stimulates antigen-presenting cells such as dendritic cells, resulting in the upregulation of costimulatory molecules and the production of various inflammatory cytokines required for CD4+ T cell priming in vivo. However, CD40L- or CD40-deficient mice challenged with viruses mount protective CD4+ T cell responses that produce normal levels of interferon γ, suggesting a CD40L/CD40-independent mechanism of CD4+ T cell priming that to date has not been elucidated. Here we show that CD4+ T cell responses to viral infection were greatly diminished in CD40-deficient mice by administration of a soluble form of TNF-related activation-induced cytokine receptor (TRANCE-R) to inhibit the function of another TNF family member, TRANCE. Thus, the TRANCE/TRANCE-R interaction provides costimulation required for efficient CD4+ T cell priming during viral infection in the absence of CD40L/CD40. These results also indicate that not even the potent inflammatory microenvironment induced by viral infections is sufficient to elicit efficient CD4+ T cell priming without proper costimulation provided by the TNF family (CD40L or TRANCE). Moreover, the data suggest that TRANCE/TRANCE-R may be a novel and important target for immune intervention

TRANCE (Tumor necrosis factor [TNF]-related Activation-induced Cytokine), a new TNF family member predominantly expressed in t cells, is a dendritic cell-specific survival factor

TRANCE (tumor necrosis factor [TNF]-related activation-induced cytokine) is a new member of the TNF family that is induced upon T cell receptor engagement and activates c-Jun N-terminal kinase (JNK) after interaction with its putative receptor (TRANCE-R). In addition, TRANCE expression is restricted to lymphoid organs and T cells. Here, we show that high levels of TRANCE-R are detected on mature dendritic cells (DCs) but not on freshly isolated B cells, T cells, or macrophages. Signaling by TRANCE-R appears to be dependent on TNF receptor-associated factor 2 (TRAF2), since JNK induction is impaired in cells from transgenic mice overexpressing a dominant negative TRAF2 protein. TRANCE inhibits apoptosis of mouse bone marrow-derived DCs and human monocyte-derived DCs in vitro. The resulting increase in DC survival is accompanied by a proportional increase in DC-mediated T cell proliferation in a mixed leukocyte reaction. TRANCE upregulates Bcl-X(L) expression, suggesting a potential mechanism for enhanced DC survival. TRANCE does not induce the proliferation of or increase the survival oft or B cells. Therefore, TRANCE is a new DC-restricted survival factor that mediates T cell-DC communication and may provide a tool to selectively enhance DC activity

The TRAF family of signal transducers mediates NF-κB activation by the TRANCE receptor

Tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE), a member of the TNF family expressed on activated T-cells, bone marrow stromal cells, and osteoblasts, regulates the function of dendritic cells (DC) and osteoclasts. The TRANCE receptor (TRANCE-R), recently identified as receptor activator of NF-κβ (RANK), activates NF-κB, a transcription factor critical in the differentiation and activation of those cells. In this report we identify the TNF receptor-associated factor (TRAF) family of signal transducers as important components of TRANCE-R-mediated NF- κB activation. Coimmunoprecipitation experiments suggested potential interactions between the cytoplasmic tail of TRANCE-R with TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6. Dominant negative forms of TRAF2, TRAF5, and TRAF6 and an endogenous inhibitor of TRAF2, TRAF-interacting protein (TRIP), substantially inhibited TRANCE-R-mediated NF-κB activation, suggesting a role of TRAFs in regulating DC and osteoclast function. Overexpression of combinations of TRAF dominant negative proteins revealed competition between TRAF proteins for the TRANCE-R and the possibility of a TRAF-independent NF- κB pathway. Analysis of TRANCE-R deletion mutants suggested that the TRAF2 and TRAF5 interaction sites were restricted to the C-terminal 93 amino acids (C-region). TRAF6 also complexed to the C-region in addition to several regions N-terminal to the TRAF2 and TRAF5 association sites. Furthermore, transfection experiments with TRANCE-R deletion mutants revealed that multiple regions of the TRANCE-R can mediate NF-κB activation

Hybrid Deep Neural Network for Brachial Plexus Nerve Segmentation in Ultrasound Images

Ultrasound-guided regional anesthesia (UGRA) can replace general anesthesia (GA), improving pain control and recovery time. This method can be applied on the brachial plexus (BP) after clavicular surgeries. However, identification of the BP from ultrasound (US) images is difficult, even for trained professionals. To address this problem, convolutional neural networks (CNNs) and more advanced deep neural networks (DNNs) can be used for identification and segmentation of the BP nerve region. In this paper, we propose a hybrid model consisting of a classification model followed by a segmentation model to segment BP nerve regions in ultrasound images. A CNN model is employed as a classifier to precisely select the images with the BP region. Then, a U-net or M-net model is used for the segmentation. Our experimental results indicate that the proposed hybrid model significantly improves the segmentation performance over a single segmentation model.Comment: The first two authors contributed equall

Contributing factors to influenza vaccine uptake in general hospitals:an explorative management questionnaire study from the Netherlands

BACKGROUND: The influenza vaccination rate in hospitals among health care workers in Europe remains low. As there is a lack of research about management factors we assessed factors reported by administrators of general hospitals that are associated with the influenza vaccine uptake among health care workers. METHODS: All 81 general hospitals in the Netherlands were approached to participate in a self-administered questionnaire study. The questionnaire was directed at the hospital administrators. The following factors were addressed: beliefs about the effectiveness of the influenza vaccine, whether the hospital had a written policy on influenza vaccination and how the hospital informed their staff about influenza vaccination. The questionnaire also included questions about mandatory vaccination, whether it was free of charge and how delivered as well as the vaccination campaign costs. The outcome of this one-season survey is the self-reported overall influenza vaccination rate of health care workers. RESULTS: In all, 79 of 81 hospitals that were approached were willing to participate and therefore received a questionnaire. Of these, 42 were returned (response rate 52%). Overall influenza vaccination rate among health care workers in our sample was 17.7% (95% confidence interval: 14.6% to 20.8%). Hospitals in which the administrators agreed with positive statements concerning the influenza vaccination had a slightly higher, but non-significant, vaccine uptake. There was a 9% higher vaccine uptake in hospitals that spent more than €1250,- on the vaccination campaign (24.0% versus 15.0%; 95% confidence interval from 0.7% to 17.3%). CONCLUSIONS: Agreement with positive statements about management factors with regard to influenza vaccination were not associated with the uptake. More economic investments were related with a higher vaccine uptake; the reasons for this should be explored further

Experienced Burden of and Adherence to Smartphone-Based Ecological Momentary Assessment in Persons with Affective Disorders

(1) Background: The use of smartphone-based ecological momentary assessment (EMA) questionnaires in affective disorder research has rapidly increased. Though, a thorough understanding of experienced burden of and adherence to EMA is crucial in determining the usefulness of EMA. (2) Methods: Persons with current affective disorders (n = 100), remitted persons (n = 190), and healthy controls (n = 94) participated in a smartphone-based EMA two-week monitoring period. Our primary outcomes were (momentary) perceived burden of and adherence to EMA. (3) Results: In the whole sample, lower positive and higher negative affect were associated with slightly higher levels of perceived momentary burden (B = -0.23 [95%CI = -0.27-0.19], B = 0.30 [95%CI = 0.24-0.37], respectively). The persons with current affective disorders reported slightly higher levels of experienced momentary burden (Mdn = 1.98 [IQR = 1.28-2.57]), than the remitted persons (Mdn = 1.64 [IQR = 1.11-2.24]) and healthy controls (Mdn = 1.28 [IQR = 1.04-1.92]). Nevertheless, the persons with current affective disorders still showed very high adherence rates (Mdn = 94.3% [IQR = 87.9-97.1]), at rates on a par with the remitted persons (Mdn = 94.3% [IQR = 90.0-97.1]) and healthy controls (Mdn = 94.3% [IQR = 90.0-98.6]). (4) Discussion: Frequent momentary questionnaires of mental well-being are slightly more burdensome to the persons with current affective disorders, but this does not seem to have a negative impact on adherence. Their high rate of adherence to EMA-which was similar to that in remitted persons and healthy controls -suggests that it is feasible to apply (short-duration) EMA