Differences in acute phase response to bacterial, fungal and viral antigens in greater mouse-eared bats (Myotis myotis)

The acute phase response (APR) is an evolutionarily well-conserved part of the innate immune defense against pathogens. However, recent studies in bats yielded surprisingly diverse results compared to previous APR studies on both vertebrate and invertebrate species. This is especially interesting due to the known role of bats as reservoirs for viruses and other intracellular pathogens, while being susceptible to extracellular microorganisms such as some bacteria and fungi. To better understand these discrepancies and the reservoir-competence of bats, we mimicked bacterial, viral and fungal infections in greater mouse-eared bats (Myotis myotis) and quantified different aspects of the APR over a two-day period. Individuals reacted most strongly to a viral (PolyI:C) and a bacterial (LPS) antigen, reflected by an increase of haptoglobin levels (LPS) and an increase of the neutrophil-to-lymphocyte-ratio (PolyI:C and LPS). We did not detect fever, leukocytosis, body mass loss, or a change in the overall functioning of the innate immunity upon challenge with any antigen. We add evidence that bats respond selectively with APR to specific pathogens and that the activation of different parts of the immune system is species-specific

Constructing a Distant Future: Imaginaries in Geoengineering

We develop the concept of the distant future as a new way of seeing the future in collective efforts. While a near future is represented in practical terms and concerned with forming expectations and goals under conditions of uncertainty, a distant future is represented in stylized terms and concerned with imagining possibilities under conditions of ambiguity. Management research on future-oriented action has developed around problems of the near future. To explore distant futures, we analyze the case of geoengineering, a set of planetary-scale technologies that have been proposed as solutions to the threat of climate change. Geoengineering has increasingly been treated as if it were a reality, despite continued controversy and in the absence of any implementation. We find that societal-level imaginaries that were built on deeply-held moral bases and cosmologies underpinned the conception of geoengineering, and that a dialectic process of discursive attempts to reconcile oppositional imaginaries increased the concreteness and credibility of geoengineering so that it increasingly has been treated as an ‘as-if’ reality. We suggest that distant futures orient collective efforts in distinctive ways, not as concrete guides for action but by expressing critiques and alternatives, that can become treated as ‘as-if’ realities

Soil-Transmitted Helminth Reinfection after Drug Treatment: A Systematic Review and Meta-Analysis

Infections with soil-transmitted helminths (the roundworm Ascaris lumbricoides, the whipworm Trichuris trichiura, and hookworm) affect over 1 billion people, particularly rural communities in the developing world. The global strategy to control soil-transmitted helminth infections is ‘preventive chemotherapy’, which means large-scale administration of anthelmintic drugs to at-risk populations. However, because reinfection occurs after treatment, ‘preventive chemotherapy’ must be repeated regularly. Our systematic review and meta-analysis found that at 3, 6, and 12 months after treatment, A. lumbricoides prevalence reached 26% (95% confidence interval (CI): 16–43%), 68% (95% CI: 60–76%) and 94% (95% CI: 88–100%) of pretreatment levels, respectively. For T. trichiura, respective reinfection prevalence at these time points were 36% (95% CI: 28–47%), 67% (95% CI: 42–100%), and 82% (95% CI: 62–100%); and for hookworm, 30% (95% CI: 26–34%), 55% (95% CI: 34–87%), and 57% (95% CI: 49–67%). Prevalence and intensity of reinfection were positively correlated with pretreatment infection status. Our results suggest a frequent anthelmintic drug administration to maximize the benefit of preventive chemotherapy. Moreover, an integrated control strategy, consisting of preventive chemotherapy combined with health education and environmental sanitation is needed to interrupt transmission of soil-transmitted helminths

Bayes factors for mixed models: A discussion

van Doorn et al. (2021) outlined various questions that arise when conducting Bayesian model comparison for mixed effects models. Seven response articles offered their own perspective on the preferred setup for mixed model comparison, on the most appropriate specification of prior distributions, and on the desirability of default recommendations. This article presents a round-table discussion that aims to clarify outstanding issues, explore common ground, and outline practical considerations for any researcher wishing to conduct a Bayesian mixed effects model comparison

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Paradoxes of Management and Organization: Short cases for pedagogical use

The world is rich in paradox, tension and contradiction (Jarzabkowski, Lê, &amp; Van de Ven, 2013). For this reason, the capacity to handle paradox is being presented as an important management competence. With this series, the European Forum on Paradox and Plurality aims to contribute to the development of paradox management competences by producing teaching materials on management tension and paradox. In this short introductory note we define basic concepts for the beginner. The management of paradox, defined as the persistent interplay of mutually defining opposites (Smith &amp; Lewis, 2011), such as stability and change or exploration and exploitation, constitutes a managerial imperative. Managers as well as organizational members in general, may assume or ignore the paradox lens but tensions and contradictions are unavoidable in complex systems. The exploration of the role of tensions, contradictions and paradoxes in organizations has now produced a rich bibliography (Putnam et al., 2016; Schad et al., 2016). For readers new to the theory of organizational paradox we present a brief introductory bibliography (see Box 1). For this reason, organizations are in some cases trying to develop ways of dealing with challenges such as when they have to maintain resilience in face of crisis (Giustiniano et al., 2020), cultivate ambidexterity (Raisch &amp; Birkinshaw, 2008) or try to go agile while maintaining robust routines (Rigby et al., 2020). When successfully balanced, the articulation of opposite demands may constitute a source of advantage. But their articulation is difficult and success in tackling opposition cannot be guaranteed, as some tensions cannot be integrated and their ongoing articulation is difficult. As Cunha and Putnam (2019) have pointed out, paradox cannot be tamed

Using Social Indicators to Evaluate the Effectiveness of Outreach in Two Indiana Watersheds

Nonpoint source pollution is recognized as one of the greatest threats to water quality in the United States. Outreach is one tool that can be used to help increase public awareness and motivate action towards addressing water issues. In order to create effective outreach, we must understand public perceptions of water quality, perceived barriers to implementing environmental solutions, and what types of outreach best connect with target audiences. In 2010, social indicator surveys were distributed in two watersheds in Indiana to gather baseline data on urban and agricultural residents\u27 attitudes towards and usage of water quality conservation practices. Local watershed organizations then used various outreach methods to encourage residents to implement specific practices. In 2014, post‐project surveys were conducted in both watersheds to assess whether the outreach efforts had been effective. Even with outreach efforts, many residents still were unaware that specific water pollutants were problems in their watershed. There were, however, positive changes in overall water quality attitudes. Changes in awareness and adoption of conservation practices varied by watershed and resident type, yet generally moved in a positive direction or were unchanged. The primary barrier to practice adoption for all respondents was cost. Outreach events were generally not well attended and did little to change attendee behavior. Some outreach activities seem to be more useful than others in terms of self‐reported effectiveness while others are clearly visible to the community and may be a helpful way to raise awareness

Specificity and Mechanism of Immunoglobulin M (IgM)- and IgG-Dependent Protective Immunity to Larval Strongyloides stercoralis in Mice

Protective immunity in mice to the infective third-stage larvae (L3) of Strongyloides stercoralis was shown to be dependent on immunoglobulin M (IgM), complement activation, and granulocytes. The objectives of the present study were to determine whether IgG was also a protective antibody isotype and to define the specificity and the mechanism by which IgG functions. Purified IgG recovered from mice 3 weeks after a booster immunization with live L3 was shown to transfer high levels of protective immunity to naïve mice. IgG transferred into mice treated to block complement activation or to eliminate granulocytes failed to kill the challenge larvae. Transfer of immune IgG into IL-5 knockout (KO) mice, which are deficient in eosinophils, resulted in larval attrition, while transfer into FcRγ KO mice did not result in larval killing. These findings suggest that IgG from mice immunized with live L3 requires complement activation and neutrophils for killing of L3 through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. This is in contrast to the results of investigations using IgM from mice immunized with live L3 and IgG from mice immunized with larval antigens soluble in deoxycholate in which protective immunity was shown to be ADCC independent. Western blot analyses with immune IgM and IgG identified few antigens recognized by all protective antibody isotypes. Results from immunoelectron microscopy demonstrated that the protective antibodies bound to different regions in the L3. It was therefore concluded that while IgM and IgG antibodies are both protective against larval S. stercoralis, they recognize different antigens and utilize different killing mechanisms