The B subunit of Escherichia coli heat-labile toxin alters the development and antigen-presenting capacity of dendritic cells

Escherichia coli’s heat-labile enterotoxin (Etx) and its non-toxic B subunit (EtxB) have been characterized as adjuvants capable of enhancing T cell responses to co-administered antigen. Here, we investigate the direct effect of intravenously administered EtxB on the size of the dendritic and mye-loid cell populations in spleen. EtxB treatment appears to enhance the development and turnover of dendritic and myeloid cells from precursors within the spleen. EtxB treatment also gives a dendritic cell (DC) population with higher viability and lower activation status based on the reduced expression of MHC-II, CD80 and CD86. In this respect, the in vivo effect of EtxB differs from that of the highly inflammatory mediator lipopolysaccharide. In in vi-tro bone marrow cultures, EtxB treatment was also found to enhance the development of DC from precursors dependent on Flt3L. In terms of the in vivo effect of EtxB on CD4 and CD8 T cell responses in mice, the interaction of EtxB directly with DC was demonstrated following conditional deple-tion of CD11c+ DC. In summary, all results are consistent with EtxB displaying adjuvant ability by enhancing the turnover of DC in spleen, leading to newly mature myeloid and DC in spleen, thereby increasing DC capacity to perform as antigen-presenting cells on encounter with T cells

Investigation into the prevalence of a novel dendritic-like cell subset in vivo

A novel dendritic-like cell subset termed L-DC was recently identified in murine spleen based on marker expression of a homogeneous cell population derived from long-term culture of neonatal spleen. The function of L-DC is distinct from other splenic dendritic and myeloid cell subsets because of their high endocytic capacity and their ability to cross-present antigen to CD8+ T cells. This paper shows the subset to be unique to spleen and blood, with a similar, but possibly functionally distinct subset also present in bone marrow. The prevalence of the subset is low; ~6% of all dendritic and myeloid cells in the spleen and ~5% in blood. However, they are a distinct cell type on the basis of marker expression, and endocytic and T-cell stimulatory capacity. Attempts to identify an enriched population of these cells in mutant mouse strains with reported increases in myelopoiesis showed either a lack of L-DC or an altered phenotype reflective of the phenotype of the mouse strain

Whose act(ion)? Report on intercultural educators in critical conversation on ethical practice across disciplines

This piece introduces and recreates a critical dialogue which occurred in the summer of 2021 among educational practitioners at the University of Rhode Island (USA), during an interdisciplinary teach-in retreat on Intercultural Competence Development for Teachers and Learners. The authors were among the participants who collaborated on this project led by Anna Santucci; here, they offer a snapshot of the exchange that took place on the final day of the retreat. The themes that emerged throughout the teach-in, summarized in that closing conversation, significantly resonate with the RISE Manifesto (Cañas, 2015). These themes include salient values, skills, and behaviors of interculturally competent educators and scholars whose understanding of ethical practice is grounded in empathy, and whose work strives to embrace radical creativity in envisioning possibilities for co-creation among all participants in the teaching and/or research experience – enacting education through and for "action" via human act-ivation and, therefore, act-ivism

Spleen as a site for hematopoiesis of a distinct antigen presenting cell type

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen

Small Group Learning is Associated with Reduced Salivary Cortisol and Testosterone in Undergraduate Students

Small group learning activities have been shown to improve student academic performance and educational outcomes. Yet, we have an imperfect understanding of the mechanisms by which this occurs. Group learning may mediate student stress by placing learning in a context where students have both social support and greater control over their learning. We hypothesize that one of the methods by which small group activities improve learning is by mitigating student stress. To test this, we collected physiological measures of stress and self-reported perceived stress from 26 students in two undergraduate classes. Salivary cortisol and testosterone were measured within students across five contexts: a) pre-instructional baseline, b) following a traditional lecture, c) after participating in a structured small group learning activity, d) following completion of multiple choice, and e) essay sections of an exam. Results indicate students have lower salivary cortisol after small group learning activities, as compared to traditional lectures. Further, there is no evidence of a relationship between physiological measures of stress and self-reported perceived stress levels. We discuss how structured small group activities may be beneficial for reducing stress and improving student-learning outcomes

Conditional probabilities in Ponzano-Regge minisuperspace

We examine the Hartle-Hawking no-boundary initial state for the Ponzano-Regge formulation of gravity in three dimensions. We consider the behavior of conditional probabilities and expectation values for geometrical quantities in this initial state for a simple minisuperspace model consisting of a two-parameter set of anisotropic geometries on a 2-sphere boundary. We find dependence on the cutoff used in the construction of Ponzano-Regge amplitudes for expectation values of edge lengths. However, these expectation values are cutoff independent when computed in certain, but not all, conditional probability distributions. Conditions that yield cutoff independent expectation values are those that constrain the boundary geometry to a finite range of edge lengths. We argue that such conditions have a correspondence to fixing a range of local time, as classically associated with the area of a surface for spatially closed cosmologies. Thus these results may hint at how classical spacetime emerges from quantum amplitudes.Comment: 26 pages including 10 figures, some reorganization in the presentation of results, expanded discussion of results in the context of 2+1 gravity in the Witten variables, 3 new reference

Spleen as a Site for Hematopoiesis of a Distinct Antigen Presenting Cell Type

While spleen and other secondary tissue sites contribute to hematopoiesis, the nature of cells produced and the environment under which this happens are not fully defined. Evidence is reviewed here for hematopoiesis occurring in the spleen microenvironment leading to the production of tissue-specific antigen presenting cells. The novel dendritic-like cell identified in spleen is phenotypically and functionally distinct from other described antigen presenting cells. In order to identify these cells as distinct, it has been necessary to show that their lineage origin and progenitors differ from that of other known dendritic and myeloid cell types. The spleen therefore represents a distinct microenvironment for hematopoiesis of a novel myeloid cell arising from self-renewing hematopoietic stem cells (HSC) or progenitors endogenous to spleen

IP-10/CXCL10 induction in human pancreatic cancer stroma influences lymphocytes recruitment and correlates with poor survival

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant desmoplastic reaction driven by pancreatic stellate cells (PSCs) that contributes to tumor progression. Here we sought to characterize the interactions between pancreatic cancer cells (PCCs) and PSCs that affect the inflammatory and immune response in pancreatic tumors. Conditioned media from mono- and cocultures of PSCs and PCCs were assayed for expression of cytokines and growth factors. IP-10/CXCL10 was the most highly induced chemokine in coculture of PSCs and PCCs. Its expression was induced in the PSCs by PCCs. IP-10 was elevated in human PDAC specimens, and positively correlated with high stroma content. Furthermore, gene expression of IP-10 and its receptor CXCR3 were significantly associated with the intratumoral presence of regulatory T cells (Tregs). In an independent cohort of 48 patients with resectable pancreatic ductal adenocarcinoma, high IP-10 expression levels correlated with decreased median overall survival. Finally, IP-10 stimulated the ex vivo recruitment of CXCR3+ effector T cells as well as CXCR3+ Tregs derived from patients with PDAC. Our findings suggest that, in pancreatic cancer, CXCR3+ Tregs can be recruited by IP-10 expressed by PSCs in the tumor stroma, leading to immunosuppressive and tumor-promoting effects

Emerging professional skills: Insights and methods

In this workshop run by the Engineering skills SIG, attendees were given the opportunity to learn about emerging professional competencies, and strategies to overcome teaching barriers.The workshop format was “world cafe” with several tables for small groups to informally discuss these strategies within a time limit. Each table focussed on an emerging skill and/or scenario and participants each visited several tables. The session was informed by the engineering skills survey taken by SEFI 2021 conference attendees. It gave us views on new competencies, barriers to teaching them, and illustrations of good practice. Obstacles to teaching them include motivation, legitimacy, overloaded curriculums, student resistance, resource constraints, and pedagogical understandings.Ideally skills should be learned by students in contexts where they’re used. While many technical competencies are primarily developed in engineering practice, professional/soft abilities are often not. As a result, there ought to be some opportunity for the student to transfer, adapt and (re)learn them in an engineering degree. This report summarises the conference workshop outputs with sections for each table. Each section acknowledges the hosts/authors, a summary of the discussion, and any materials presented. Readers may find this paper useful when facilitating related discussions

Who, What, How? Tackling Skills Challenges: Future Relevance, Stakeholder Differences, And Teaching Hurdles

The Engineering Skills Special Interest Group (SIG) ran a workshop on the current challenges in teaching engineering skills. This workshop employed the “world café” participatory method where attendees visited three tables for a structured discussion with a member of the SIG. Each table posed a different question: On the What? table we discussed which skills are most relevant for future practitioners. The Who? table focussed on the differences in the way that various professional skills are conceptualised by main stakeholders. Finally, at the How? table we discussed the facilitators and barriers in designing and delivering skills education. The outcome of the workshop presented here is a mapping of skills in terms of present and future importance to attendees and their countries, and a classification of stakeholders in terms of macro, meso, micro level when considering their influence over skill conceptualisation and realisation