Post-Conflict Affiliation by Chimpanzees with Aggressors: Other-Oriented versus Selfish Political Strategy

Consolation, i.e., post-conflict affiliation directed from bystanders to recent victims of aggression, has recently acquired an important role in the debate about empathy in great apes. Although similar contacts have been also described for aggressors, i.e., appeasement, they have received far less attention and their function and underlying mechanisms remain largely unknown. An exceptionally large database of spontaneous conflict and post-conflict interactions in two outdoor-housed groups of chimpanzees lends support to the notion that affiliation toward aggressors reduces the latter's aggressive tendencies in that further aggression was less frequent after the occurrence of the affiliation. However, bystander affiliation toward aggressors occurred disproportionally between individuals that were socially close (i.e., affiliation partners) which suggest that it did not function to protect the actor itself against redirected aggression. Contrary to consolation behavior, it was provided most often by adult males and directed toward high ranking males, whereas females engaged less often in this behavior both as actors and recipients, suggesting that affiliation with aggressors is unlikely to be a reaction to the distress of others. We propose that bystander affiliation toward aggressors may function to strengthen bonds between valuable partners, probably as part of political strategies. Our findings also suggest that this post-conflict behavior may act as an alternative to reconciliation, i.e., post-conflict affiliation between opponents, in that it is more common when opponents fail to reconcile

Ravens Reconcile after Aggressive Conflicts with Valuable Partners

Reconciliation, a post-conflict affiliative interaction between former opponents, is an important mechanism for reducing the costs of aggressive conflict in primates and some other mammals as it may repair the opponents' relationship and reduce post-conflict distress. Opponents who share a valuable relationship are expected to be more likely to reconcile as for such partners the benefits of relationship repair should outweigh the risk of renewed aggression. In birds, however, post-conflict behavior has thus far been marked by an apparent absence of reconciliation, suggested to result either from differing avian and mammalian strategies or because birds may not share valuable relationships with partners with whom they engage in aggressive conflict. Here, we demonstrate the occurrence of reconciliation in a group of captive subadult ravens (Corvus corax) and show that it is more likely to occur after conflicts between partners who share a valuable relationship. Furthermore, former opponents were less likely to engage in renewed aggression following reconciliation, suggesting that reconciliation repairs damage caused to their relationship by the preceding conflict. Our findings suggest not only that primate-like valuable relationships exist outside the pair bond in birds, but that such partners may employ the same mechanisms in birds as in primates to ensure that the benefits afforded by their relationships are maintained even when conflicts of interest escalate into aggression. These results provide further support for a convergent evolution of social strategies in avian and mammalian species

Crown Lengthening Revisited

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141178/1/cap0233.pd

Temozolomide followed by combined immunotherapy with GM-CSF, low-dose IL2 and IFNα in patients with metastatic melanoma

The purpose of this study is to determine the toxicity and efficacy of temozolomide (TMZ) p.o. followed by subcutaneous (s.c.) low-dose interleukin-2 (IL2), granulocyte-monocyte colony stimulating factor (GM-CSF) and interferon-alpha 2b (IFN alpha) in patients with metastatic melanoma. A total of 74 evaluable patients received, in four separate cohorts, escalating doses of TMZ (150-250 mg m(-2)) for 5 days followed by s.c. IL2 (4 MIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFN alpha (5 MIU flat) for 12 days. A second identical treatment was scheduled on day 22 and cycles were repeated in stable or responding patients following evaluation. Data were analysed after a median follow-up of 20 months (12-30 months). The overall objective response rate was 31% (23 out of 74; confidence limits 20.8-42.9%) with 5% CR. Responses occurred in all disease sites including the central nervous system (CNS). Of the 36 patients with responding or stable disease, none developed CNS metastasis as the first or concurrent site of progressive disease. Median survival was 252 days (8.3 months), 1 year survival 41%. Thrombocytopenia was the primary toxicity of TMZ and was dose- and patient-dependent. Lymphocytopenia (grade 3-4 CTC) occurred in 48.5% (34 out of 70) fully monitored patients following TMZ and was present after immunotherapy in two patients. The main toxicity of combined immunotherapy was the flu-like syndrome (grade 3) and transient liver function disturbances (grade 2 in 20, grade 3 in 15 patients). TMZ p.o. followed by s.c. combined immunotherapy demonstrates efficacy in patients with stage IV melanoma and is associated with toxicity that is manageable on an outpatient basi

Renal cell carcinoma induces interleukin 10 and prostaglandin E2 production by monocytes

Immunotherapy with interleukin 2 (IL-2) is not an effective anti-cancer treatment in the majority of patients with renal cell carcinoma (RCC), suggesting that the activation of cytotoxic T cells or NK cells may be impaired in vivo in these patients. The production of immunosuppressive factors by RCC was investigated. Using immunohistochemistry, IL-10 was detectable in 10 of 21 tumour samples tested. IL-10 was undetectable in the supernatant of cell lines derived from these RCCs. However, these cell lines or their conditioned medium (RCC CM), but not normal renal epithelial cells adjacent to the RCC or breastcarcinoma cell lines, were found to induce IL-10, as well as prostaglandin E2 (PGE2) and tumour necrosis factor (TNF)α production by autologous or allogeneic peripheral blood mononuclear cells (PBMCs) and monocytes. IL-10 production induced by RCC CM was found to be dependent on TNF-α and PGE2 since an anti-TNF-α antibody (Ab) inhibited 40–70% of IL-10 production by monocytes, and the combination of anti-TNF-α Ab and indomethacin, an inhibitor of PGE2 production, inhibited 80–94% of RCC CM-induced IL-10 production by monocytes. The RCC CM of the five cell lines tested were found to induce a down-regulation of the expression of HLA-DR and CD86, as well as a strong inhibition of mannose receptor-dependent endocytosis by monocytes. The blockade of HLA-DR and CD86 expression was partially abrogated by indomethacin and anti-IL-10 Ab respectively, and completely abrogated by an anti-TNF-α Ab. The inhibition of mannose receptor-dependent endocytosis was partially abrogated by an anti-IL-10 Ab and completely abrogated by an anti-TNF-α Ab. These esults indicate that RCCs induce IL-10, PGE2 and TNF-α production by monocytes, which down-regulate the expression of cell-surface molecules involved in antigen presentation as well as their endocytic capacity. © 1999 Cancer Research Campaig

Survival of massive allografts in segmental oncological bone defect reconstructions

Reconstructions of large segmental bone defects after resection of bone tumours with massive structural allografts have a high number of reported complications including fracture, infection and non-union. Our goal is to report the survival and complications of massive allografts in our patients. A total of 32 patients were evaluated for fracture, infection, non-union rate and survival of their massive allograft reconstructions. The average follow-up for this group was five years and three months. The total fracture rate was 13% with a total infection rate of 16%. We found a low union rate of 25%. The total survival of the allografts was 80.8% (± 18.7%) after five years. We found a five-year allograft survival of 80.8% which is comparable with other studies

Spermatogonial Stem Cell Niche and Spermatogonial Stem Cell Transplantation in Zebrafish

Background Spermatogonial stem cells (SSCs) are the foundation of spermatogenesis, and reside within a specific microenvironment in the testes called “niche” which regulates stem cell properties, such as, self-renewal, pluripotency, quiescence and their ability to differentiate. Methodology/Principal Findings Here, we introduce zebrafish as a new model for the study of SSCs in vertebrates. Using 5′-bromo-2′-deoxyuridine (BrdU), we identified long term BrdU-retaining germ cells, type A undifferentiated spermatogonia as putative stem cells in zebrafish testes. Similar to rodents, these cells were preferentially located near the interstitium, suggesting that the SSC niche is related to interstitial elements and might be conserved across vertebrates. This localization was also confirmed by analyzing the topographical distribution of type A undifferentiated spermatogonia in normal, vasa::egfp and fli::egfp zebrafish testes. In the latter one, the topographical arrangement suggested that the vasculature is important for the SSC niche, perhaps as a supplier of nutrients, oxygen and/or signaling molecules. We also developed an SSC transplantation technique for both male and female recipients as an assay to evaluate the presence, biological activity, and plasticity of the SSC candidates in zebrafish. Conclusions/Significance We demonstrated donor-derived spermato- and oogenesis in male and female recipients, respectively, indicating the stemness of type A undifferentiated spermatogonia and their plasticity when placed into an environment different from their original niche. Similar to other vertebrates, the transplantation efficiency was low. This might be attributed to the testicular microenvironment created after busulfan depletion in the recipients, which may have caused an imbalance between factors regulating self-renewal or differentiation of the transplanted SSCs

The distinct role of CD4+ and CD8+ T-cells during the anti-tumour effects of targeted superantigens

To target T-cells to the tumour area we created a recombinant protein of the bacterial superantigen (SAg) Staphylococcal enterotoxin A (SEA) and the Fab-fragment of a tumour-reactive antibody. This antibody-targeted SAg immunotherapy therapy has been shown to be highly efficient, eliminating > 95% of the pulmonary metastasis in mice carrying established melanoma micrometastases. Earlier studies demonstrated that elimination of the C215-expressing B16-melanoma lung metastasis was dependent on interferon (IFN)-γ release and expression of perforin. In the present study, therapeutic effector functions were analysed both locally at the tumour site and systemically in the spleen. In order to elucidate the role of each T-cell subset during Fab–SEA therapy, CD4 knock-out (KO) and CD8 KO mice were used. Tumour size reduction was statistically significant in Fab–SEA-based tumour therapy in both types of T-cell-deficient mice compared to wild-type mice. CD4 KO mice displayed a drastic reduction in the number of tumour-infiltrating macrophages and CD8+ T-cells. Therapy-induced accumulation of perforin-containing cells at the tumour site was significantly impaired in CD8 KO mice, and marginally in CD4 KO mice. Moreover, CD4 KO mice failed to produce substantial amounts of the tumour suppressive cytokine IFN-γ. This is in sharp contrast to normal mice where a massive local release was recorded. CD8 KO mice displayed a spontaneous production of interleukin (IL)-4 and IL-10 locally in the tumour. Neither normal nor CD4 KO mice produced detectable levels of these Th-2-associated cytokines. The high level of IL-10 was demonstrated to inhibit Fab–SEA tumour therapy, since the therapeutic efficacy was significantly higher in IL-10 KO mice. These results illustrate the importance of a finely tuned cellular collaboration to regulate the various phases of an efficient anti-tumour immune response. © 1999 Cancer Research Campaig