Notes

Insulin-producing β-cells replenish ectopically from a mesodermal origins beneath the perturbation of hemato-endothelial standards.
As a result, DOX-TTPNs efficiently re-sensitized TRAIL-resistant tumor cells to TRAIL-mediated apoptosis in vitro by regulating levels of the TRAIL receptor, DR5, and anti- and pro-apoptotic proteins involved in extrinsic and intrinsic apoptosis pathways. We further demonstrated the antitumor efficacy of DOX-TTPNs in vivo, showing that even at a very low dose, the incorporated DOX successfully re-sensitized tumors to the apoptotic effects of TRAIL, underscoring the potential of this platform as an antitumor agent. Given that other homotrimeric TNF superfamily ligands and immunotherapeutic agents can be substituted for TRAIL ligand and re-sensitizing drugs on the surface and in the inner cavity of the nanocage, respectively, this platform is potentially suitable for development of a broad range of anticancer or immunotherapeutic combinations.Although the cause of multiple sclerosis (MS) is unclear, an autoimmune attack on myelin-based coating layers of nerve cells in the brain and spinal cord is the main feature of the disease, highlighting modulation of the immune response to myelin as a feasible therapeutic approach. Here, we report the potential of bilirubin nanoparticles (BRNPs) based on the endogenous antioxidant and anti-inflammatory agent, bilirubin, as a therapeutic nanomedicine for MS. In a mouse model of experimental autoimmune encephalomyelitis (EAE), multiple intravenous injections of BRNPs significantly delayed disease onset and suppressed disease progression and severity as well as disease incidence rate without systemic immunosuppression. Following intravenous injection, BRNPs accumulated more extensively and were retained longer in secondary lymphoid organs of EAE-induced mice compared with non-immunized control mice, including in inguinal lymph nodes (iLNs) and spleens, where antigen presenting cells (APCs) activated by the myelin antigen are abundant. see more Studies of the underlying mechanism of action further revealed that BRNPs negatively regulated the differentiation of naïve CD4+ T cells into T helper 17 (Th17) cells by inhibiting maturation of APCs through scavenging of reactive oxygen species (ROS) overproduced in both dendritic cells (DCs) and macrophages upon antigen uptake. These findings indicate that BRNPs have the potential to be used as a new therapeutic nanomedicine for treatment of various CD4+ T cell-associated autoimmune diseases.Two Pavlovian appetitive conditioning experiments with rats assessed extinction cue (EC) transfer using spontaneous recovery tests. In each experiment, after conditioned stimulus (CS) A-US pairings, an EC (X) was presented during A-extinction, followed by spontaneous recovery testing with A. Experiment 1 tested for transfer between ECs; the additional CS (B) was conditioned and then was extinguished with a second EC (Y). CS A was tested with X and with Y (the possible transfer EC). Experiment 2 tested for transfer between an EC and an explicitly trained serial negative occasion setter (OS). Prior to testing with A, Y was trained in a serial Y→C-, C + discrimination; a Z→B-, B + discrimination was also trained. A was tested with X and with Y (with Y as the possible transfer OS). X and Y were also tested with B (where X with B tests possible EC-OS transfer). In each experiment Y did not reduce spontaneous recovery to A, showing no transfer of one EC to another (Experiment 1) and no transfer of a serial negative OS to a CS (A) extinguished with an EC (X; Experiment 2). X did not reduce responding to B, showing no transfer of an EC to the target CS of a serial negative OS discrimination, although Y did transfer to B (Experiment 2) showing transfer between serial OSs. X did reduce responding to the CS (A) it had occurred with during extinction (Experiments 1 and 2). The results are discussed in terms of EC characteristics and regarding theories of an EC's possible mechanisms.High-throughput sequencing technologies brought a renewed interest for immune repertoires. Fish Ab and B cell repertoires are no exception, and their comprehensive analysis can both provide new insights into poorly understood immune mechanisms, and identify markers of protection after vaccination. However, the lack of genomic description and standardized nomenclature of IG genes hampers accurate annotation of Ig mRNA deep sequencing data. Complete genome sequences of Atlantic salmon and rainbow trout (Swanson line) recently allowed us to establish a comprehensive and coherent annotation of Salmonid IGH genes following IMGT standards. Here we analyzed the IGHV, D, and J genes from the newly released genome of a second rainbow trout line (Arlee). We confirmed the validity of salmonid IGHV subgroups, and extended the description of the rainbow trout IGH gene repertoire with novel sequences, while keeping nomenclature continuity. This work provides an important resource for annotation of high-throughput Ab repertoire sequencing data.Trauma exposure is prevalent, associated with multiple forms of psychopathology, and thought to alter the neurobiological substrates of threat processing. The late positive potential (LPP) is an event-related potential (ERP) that may be a clinically useful probe of the neurobiology of threat processing. Despite evidence that combat-exposed veterans exhibit aberrant threat modulation of the LPP, no studies to date have tested the psychometric properties of the LPP in combat trauma-exposed, symptomatic veterans. The primary aim of the current study was to evaluate the reliability (internal consistency, retest reliability) and convergent validity of LPP modulation by threatening faces and scenes in two common tasks among combat-exposed veterans. Participants included 82 combat-exposed veterans who completed face-matching and emotion regulation tasks during EEG recording at baseline and twelve weeks. Internal consistencies of the early LPP time windows (1000 ms). Twelve-week retest reliabilities were fair for the early window LPPs to threatening scenes and fear faces, as well as in the late time window for fear faces. Reliabilities were better for individual condition compared to difference scores. Finally, LPPs modulated by threatening scenes and faces were unrelated. Together, these results suggest that the LPPs to threatening scenes and faces reflect distinct forms of threat processing in combat-exposed veterans, and their reliabilities for the early window indicate potential clinical utility in this population.
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