Dengue virus downregulates TNFR1- and TLR3-stimulated NF-kB activation by targeting RIPK1

Dengue virus (DENV) infection is the most prevalent arthropod-borne virus disease and is endemic in more than 100 countries. Several DENV proteins have been shown to target crucial human host proteins to evade innate immune responses and establish a productive infection. Here we report that the DENV NS3 protein targets RIPK1 (Receptor Interacting Protein Kinase I), a central mediator of inflammation and cell death, and decreases intracellular RIPK1 levels during DENV infection. The interaction of NS3 with RIPK1 results in the inhibition of NF-κB activation in response to TNFR or TLR3 stimulation. Also, we observed that the effects of NS3 on RIPK1 were independent of NS3 protease activity. Our data demonstrate a novel mechanism by which DENV suppresses normal cellular functions to evade host innate immune response

Topological Defects and Interactions in Nematic Emulsions

Inverse nematic emulsions in which surfactant-coated water droplets are dispersed in a nematic host fluid have distinctive properties that set them apart from dispersions of two isotropic fluids or of nematic droplets in an isotropic fluid. We present a comprehensive theoretical study of the distortions produced in the nematic host by the dispersed droplets and of solvent mediated dipolar interactions between droplets that lead to their experimentally observed chaining. A single droplet in a nematic host acts like a macroscopic hedgehog defect. Global boundary conditions force the nucleation of compensating topological defects in the nematic host. Using variational techniques, we show that in the lowest energy configuration, a single water droplet draws a single hedgehog out of the nematic host to form a tightly bound dipole. Configurations in which the water droplet is encircled by a disclination ring have higher energy. The droplet-dipole induces distortions in the nematic host that lead to an effective dipole-dipole interaction between droplets and hence to chaining.Comment: 17 double column pages prepared by RevTex, 15 eps figures included in text, 2 gif figures for Fig. 1

Aerodynamics of Pitching Wings: Theory and Experiments

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140444/1/6.2014-2881.pd

Cell-Mediated Immunity Generated in Response to a Purified Inactivated Vaccine for Dengue Virus Type 1

Dengue is the most prevalent arboviral disease afflicting humans, and a vaccine appears to be the most rational means of control. Dengue vaccine development is in a critical phase, with the first vaccine licensed in some countries where dengue is endemic but demonstrating insufficient efficacy in immunologically naive populations. Since virus-neutralizing antibodies do not invariably correlate with vaccine efficacy, other markers that may predict protection, including cell-mediated immunity, are urgently needed. Previously, the Walter Reed Army Institute of Research developed a monovalent purified inactivated virus (PIV) vaccine candidate against dengue virus serotype 1 (DENV-1) adjuvanted with alum. The PIV vaccine was safe and immunogenic in a phase I dose escalation trial in healthy, flavivirus-naive adults in the United States. From that trial, peripheral blood mononuclear cells obtained at various time points pre- and postvaccination were used to measure DENV-1-specific T cell responses. After vaccination, a predominant CD4+ T cell-mediated response to peptide pools covering the DENV-1 structural proteins was observed. Over half (13/20) of the subjects produced interleukin-2 (IL-2) in response to DENV peptides, and the majority (17/20) demonstrated peptide-specific CD4+ T cell proliferation. In addition, analysis of postvaccination cell culture supernatants demonstrated an increased rate of production of cytokines, including gamma interferon (IFN-γ), IL-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Overall, the vaccine was found to have elicited DENV-specific CD4+ T cell responses as measured by enzyme-linked immunosorbent spot (ELISpot), intracellular cytokine staining (ICS), lymphocyte proliferation, and cytokine production assays. Thus, together with antibody readouts, the use of a multifaceted measurement of cell-mediated immune responses after vaccination is a useful strategy for more comprehensively characterizing immunity generated by dengue vaccines

Practice-based evidence for spiritually integrated psychotherapies: examining trajectories of psychological and spiritual distress

Objective: The aims of this practice-based evidence study were to (1) examine clients’ trajectories of psychological and spiritual distress over the course of spiritually integrated psychotherapies (SIPs) and (2) explore the role of varying types of spiritual interventions in these outcomes. Method: In total, 164 practitioners of SIPs from 37 settings in a practice-research network administered the Clinically Adaptive Multidimensional Outcome Survey (Sanders et al., 2018) at each session with 1227 clients and reported their use of theoretical orientations and spiritual interventions on an after-session summary checklist. Results: Focusing on sessions over an initial 12-week period, latent growth curve modeling analyses revealed that clients, on average, experienced significant reduction of psychological distress during their engagement in SIPs with improvements occurring most sharply in the first month. Further, other findings revealed a salient reciprocal interplay with spiritual distress throughout treatment, such that clients who were struggling with their religious faith and/or spirituality (R/S) were more psychologically distressed and displayed a more attenuated and gradual pattern of symptom reduction. In such cases, clinicians frequently utilized spiritual interventions involving Basic Skills (e.g., spiritual assessment), Virtues (e.g., discuss self-control), and Religious Attachment (e.g., encourage acceptance of divine love) that were uniquely associated with clients’ rate and duration of decline in psychological and spiritual distress. Conclusions: The present findings affirm the routine effectiveness of SIPs along with highlighting the potential value of certain spiritual interventions in supporting holistic recovery among clients who want clinicians to be culturally responsive to their spiritual and/or religious identities