We have previously demonstrated that Ag-specific tolerance induced by the i.v. administration of splenocytes coupled with neuroantigens, such as mouse spinal cord homogenate, myelin basic protein (MBP), and proteolipid protein, and their encephalitogenic peptides, results in dramatic inhibition of clinical and histologic signs of both actively induced and adoptively transferred relapsing experimental autoimmune encephalomyelitis (R-EAE). We report here that the administration of splenocytes coupled with mouse spinal cord homogenate (i.e., a mixture of neuroantigens), after the first paralytic episode of adoptive R-EAE triggered by MBP-specific T cells but before the appearance of the first relapse, effectively reduced the onset and severity of all subsequent relapses, as determined by both clinical and pathologic criteria. In contrast, the i.v. administration of splenocytes coupled with MBP (i.e., the specificity of the initiating T cell response), under similar conditions, effectively inhibited the initial clinical relapse, but subsequent relapses occurred with the same incidence rate and severity as those in control animals. Collectively, these results demonstrate that neuroantigen-specific tolerance is effective at specifically down-regulating an ongoing autoimmune response. This may have potential clinical applicability for treatment of autoimmune diseases. The results also support the hypothesis that the neuroantigen specificity of later relapses of R-EAE may be due to effector T cells with specificities different from those that triggered the initial clinical episode. Thus, potential therapy for the advanced stages of R-EAE, and perhaps other autoimmune diseases, may have to be directed not simply against the effector cells initiating the disease but also against effector cells with differing specificities recruited as a result of tissue damage occurring in the initial acute disease. 相似文献
Implementing new and effective control strategies to reduce populations of invasive species is needed to offset their negative impacts worldwide. The spread of Indo-Pacific lionfish (Pterois sp.) through much of the western Atlantic has been one of the most publicized marine invasions globally, and is considered a major biodiversity threat whose longer-term impacts are still uncertain. Marine managers have explored several strategies to control lionfish, such as fishing tournaments (derbies) and commercial fisheries. Commercial fisheries for invasive species are controversial because they could create perverse incentives to maintain these populations, and they have never been demonstrated to successfully control target populations. We analyzed the development and impacts of an opportunistic fishing operation aimed at commercializing invasive lionfish in the Mexican Caribbean. We examined official lionfish landings and compared them to catches from lionfish derbies and lionfish densities from locations in the state of Quintana Roo, Mexico. We found that commercial fishers, particularly from one fishing cooperative on Cozumel Island, were effective at catching lionfish, with landings peaking at 20,000 individuals in 2014. This number is comparable to the number of lionfish caught in derbies across the entire Caribbean in the same year. Ecological survey data suggest a?~?60% reduction in lionfish density on Cozumel reefs over two years (2013–2015), matching the peak landings in the lionfish fishing operation. However, the fishery’s apparent success as a control tool during the time window analyzed seemed to trigger its own demise: a decline in landings was followed by evaporating market interest and loss of economic viability. If fisheries are to be established and used as management strategies to control future invasions, managers must develop strategic collaboration plans with commercial fishing partners.
The synergistic interaction of Potato virus X (PVX) with a number of potyviruses results in systemic necrosis in Nicotiana spp. Previous investigations have indicated that the viral suppressor of RNA silencing (VSR) protein P25 of PVX triggers systemic necrosis in PVX-associated synergisms in a threshold-dependent manner. However, little is still known about the cellular processes that lead to this necrosis, and whether the VSR activity of P25 is involved in its elicitation. Here, we show that transient expression of P25 in the presence of VSRs from different viruses, including the helper component-proteinase (HC-Pro) of potyviruses, induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which ultimately lead to ER collapse. However, the host RNA silencing pathway was dispensable for the elicitation of cell death by P25. Confocal microscopy studies in leaf patches co-expressing P25 and HC-Pro showed dramatic alterations in ER membrane structures, which correlated with the up-regulation of bZIP60 and several ER-resident chaperones, including the ER luminal binding protein (BiP). Overexpression of BiP alleviated the cell death induced by the potexviral P25 protein when expressed together with VSRs derived from different viruses. Conversely, silencing of the UPR master regulator, bZIP60, led to an increase in cell death elicited by the P25/HC-Pro combination as well as by PVX-associated synergism. In addition to its role as a negative regulator of P25-induced cell death, UPR partially restricted PVX infection. Thus, systemic necrosis caused by PVX-associated synergistic infections is probably the effect of an unmitigated ER stress following the overaccumulation of a viral protein, P25, with ER remodelling activity. 相似文献
The mechanisms of the inhibitory effect of the serum thymic factor (FTS) on allograft immunity have been studied on both cellular and humoral immune responses of skin allografted mice. FTS-induced suppression of allogeneic skin graft rejection was correlated with a transient diminution of in vivo alloreactive CTL production in the spleen, whereas the generation of allo-anti-H-2 antibodies was not affected. The involvement of suppressor cells in the effect of FTS was supported by the observation that irradiated spleen cells from FTS-treated recipients (bearing a 9-day allograft) suppressed the in vitro CTL generation. 相似文献
Tolerization of SJL/J mice with splenocytes coupled with proteolipid protein (PLP), the major protein component of central nervous system myelin, resulted in dramatic inhibition of relapsing experimental autoimmune encephalomyelitis (R-EAE) induced by mouse spinal cord homogenate (MSCH). Mice tolerized with splenocytes coupled with MSCH (a complex mixture of neuroantigens) or with purified PLP, but not purified myelin basic protein, were resistant to the development of clinical and histologic R-EAE. In addition, mice rendered tolerant to an encephalitogenic peptide of PLP were significantly protected, whereas mice tolerized to a nonencephalitogenic peptide of PLP were highly susceptible, to the induction of MSCH-induced R-EAE. Thus, immune responses directed against encephalitogenic regions of PLP appear to play a major role in the development of R-EAE induced by MSCH in SJL/J mice. These results also indicate that determinant-specific immune tolerance is a feasible approach to the regulation of a disease that involves autoimmune responses to a variety of Ag. 相似文献
Kaliotoxin (KTX), a potassium channel blocker found in the venom of the scorpion Androctonous Mauretanicus is a 38 residue polypeptide with a well defined structure consisting of a alpha-helix and a three strand antiparallel beta-sheet interconnected by three disulfide bonds. Although the 3D structure has been determined by NMR, there is a number of features, mainly concerning the conformation and flexibility of the side chains, but also the long range order in the peptide and its fluctuations, that may have escaped the experimental study. These questions are now being addressed using molecular dynamics (MD) simulations. Accordingly, the present work reports the analysis of a 430 ps molecular dynamics trajectory of the polypeptide soaked with 4700 TIP3 water molecules inside a 56 A box. MD calculations were performed with periodic boundary conditions. Analysis of the conformational space sampled by each of the residues along the trajectory, suggests a special behavior of Pro17 and Lys19 both located on the helix. Furthermore, analysis of the relative movements of the secondary structure elements indicates that the alpha-helix and beta-sheets fluctuate in a correlated motion, preserving the tertiary structure of the polypeptide along the trajectory. Finally, analysis of the charge distribution was also examined. The direction of the dipole moment, computed from the center of masses appears to be an interesting feature of the structure probably related to the biological function of the molecule. 相似文献
A vast body of social and cognitive psychology studies in humans reports
evidence that external rewards, typically monetary ones, undermine intrinsic
motivation. These findings challenge the standard selfish-rationality
assumption at the core of economic reasoning. In the present work we aimed
at investigating whether the different modulation of a given monetary reward
automatically and unconsciously affects effort and performance of
participants involved in a game devoid of visual and verbal interaction and
without any perspective-taking activity.
Methodology/Principal Findings
Twelve pairs of participants were submitted to a simple motor coordination
game while recording the electromyographic activity of First Dorsal
Interosseus (FDI), the muscle mainly involved in the task. EMG data show a
clear effect of alternative rewards strategies on subjects'' motor
behavior. Moreover, participants'' stock of relevant past social
experiences, measured by a specifically designed questionnaire, was
significantly correlated with EMG activity, showing that only low social
capital subjects responded to monetary incentives consistently with a
standard rationality prediction.
Conclusions/Significance
Our findings show that the effect of extrinsic motivations on performance may
arise outside social contexts involving complex cognitive processes due to
conscious perspective-taking activity. More importantly, the peculiar
performance of low social capital individuals, in agreement with standard
economic reasoning, adds to the knowledge of the circumstances that makes
the crowding out/in of intrinsic motivation likely to occur. This may help
in improving the prediction and accuracy of economic models and reconcile
this puzzling effect of external incentives with economic theory. 相似文献