MCSF drives regulatory DC development in stromal co-cultures supporting hematopoiesis

Background: Splenic stroma overlaid with hematopoietic progenitors supports in vitro hematopoiesis with production of dendritic-like cells. Co-cultures of murine lineage-depleted bone marrow over the 5G3 stromal line produce two populations of cells, characterised as CD11b+CD11c+MHC-II− dendritic-like ‘L-DC’, and CD11b+CD11c+ MHC-II+ cells, resembling conventional dendritic cells (cDC). To date, the functional capacity of these two subsets has not been clearly distinguished. Results: Here we show both the L-DC and cDC-like subsets can be activated and induce proliferation of OT-I CD8+ T cells, being strong inducers of IL-2 and IFN-γ production. Both subsets lack ability to induce proliferation of OT-II CD4+ T cells. The cDC-like population is shown here to resemble regulatory DC in that they induce FoxP3 expression and IL10 production in OT-II CD4+ T cells, in line with their function as regulatory DC. L-DC did not activate or induce the proliferation of CD4+ T cells and did not induce FoxP3 expression in CD4+ T cells. L-DC can be distinguished from cDClike cells through their superior endocytic capacity and expression of 4-1BBL, F4/80 and Sirp-α. A comparison of gene expression by the two subsets was consistent with L-DC having an activated or immunostimulatory DC phenotype, while cDC-like cells reflect myeloid dendritic cells with inflammatory and suppressive properties, also consistent with functional characteristics as regulatory DC. When a Transwell membrane was used to prevent hematopoietic cell contact with stroma, only cDC-like cells and not L-DC were produced, and cell production was dependent on M-CSF production by stroma. Conclusion: Co-cultures of hematopoietic progenitors over splenic stroma produce two distinct subsets of dendritic-like cells. These are here distinguished phenotypically and through gene expression differences. While both resemble DC, there are functionally distinct. L-DC activate CD8+ but not CD4+ T cells, while the cDC-like population induce regulatory T cells, so reflecting regulatory DC. The latter can be enriched through Transwell co-cultures with cell production dependent on M-CSF. Keywords: Hematopoiesis, Dendritic cell, Regulatory dendritic cells, Regulatory T cellsThis work was supported by project grant #585443 to HO from the National Health and Medical Research Council of Australia. SP was supported by a graduate scholarship from the Royal Thai Government. PP was supported by an Australian National University Graduate Scholarship

Editorial:Fostering Creative Organizations: Antecedents, Processes, and Consequences of Individual and Team Creativity

Creativity, defined as the ability or process to generate novel and useful ideas, is the key engine of organizational innovation. It is a critical differentiator of mind from machine, a core driver of our uniqueness in an increasingly automated world. An important question, then, is how best to improve people's creativity, to enhance our collective innovativeness, enjoyment, and global living standards. Despite ample attention—including theory- and application-focused research—to this question, there remains much to learn about creativity..

Hematopoiesis leading to a diversity of dendritic antigen-presenting cell types

Hematopoietic stem cells (HSCs) undergo expansion and differentiation, giving rise to all terminally differentiated blood cells throughout life. HSCs are found in distinct anatomical sites during development, and in adults, hematopoiesis occurs predominantly on the luminal side of the bone cavity in bone marrow. Millions of newly formed blood cells are generated per second to accommodate the short half-life of hematopoietic cells. For this to happen, HSCs must sustain their self-renewal capacity as well as their capability to commit and differentiate toward multiple cell lineages. Development of the hematopoietic system is finely regulated as the animal ages, so that it does not become exhausted or misdirected. This review covers aspects of hematopoietic development from the embryonic period through adult life in relation to development of dendritic cells. It also considers a role for HSCs in extramedullary sites and their possible role in myelopoiesis, with formation of tissue-specific antigen-presenting cells.NHMRC (National Health and Medical Research Council of Australia

Does membership of local Chambers of Commerce networks enhance rural SME performance?:An empirical analysis

Purpose: Local Chambers of Commerce networks provide small- and medium-sized enterprises (SMEs) with an opportunity to access essential information and networking with other businesses, resulting in improved business performance. However, rural SMEs are less likely to participate in these networks and often possess lower performance. This paper aims to examine the relationship between being members of local Chambers of Commerce networks and rural SMEs’ performance by comparing business performance between rural SMEs who are members and non-members of local Chambers of Commerce networks. This paper also further explores difference in business growth plans between rural SMEs members and non-members. Design/methodology/approach: The empirical analysis draws on cross-sectional data of 3,769 rural SMEs in England and Wales from the UK's Government Longitudinal Small Business Survey 2015. Propensity score matching (PSM) is applied to control for selection bias and variations in business characteristics before comparing business performance, measured in terms of annual turnover, sale growth and profitability, between rural SMEs that are members and non-members of local Chambers of Commerce networks. Findings: Our results show that rural SME members of local Chambers of Commerce networks are more likely to grow their sales than non-members. However, they perform as good as non-members in terms of turnover and profitability. The results also emphasise that local Chambers of Commerce networks are crucial for rural SMEs to develop the skills of the workforce and leadership capability of managers, new product/service development and new working practices. Therefore, to enhance rural SMEs' performance, tailoring the services of local Chambers of Commerce to support rural businesses' needs and encouraging rural SMEs to make use of business networks are recommended. Practical implications: The paper unpacks the relationships between being local Chamber of Commerce membership and business performance, offering lessons for rural SMEs to boost their business performance and growth through participating in local business association networks. Originality/value: This paper is the first study that explores the comparative analysis of business performance and growth plans between rural SMEs that are members and non-members of the local Chamber of Commerce networks. We provide an empirical evidence-based analysis to existing literature regarding the advantages of being local Chamber of Commerce memberships to enhance business performance in rural areas.</p

Unpacking the impact of attachment to project teams on boundary-spanning behaviors

As business environments become even more competitive, project teams are required to make an effort to operate external linkages from within an organization or across organizational boundaries. Nevertheless, some members boundary-span less extensively, isolating themselves and their project teams from external environments. Our study examines why some members boundary-span more or less through the framework of group attachment theory. Data from 521 project-team members in construction and engineering industries revealed that the more individuals worry about their project team’s acceptance (group attachment anxiety), the more likely they are to perceive intergroup competition, and thus put more efforts into operating external linkages and resources to help their own teams outperform competitors. In contrast, a tendency to distrust their project teams (group attachment avoidance) generates members’ negative construal of their team’s external image, and thus fewer efforts are made at operating external linkages. Thus, project leaders and members with high group-attachment-anxiety may be best qualified for external tasks

Characterisation of dendritic cells arising from progenitors endogenous to murine spleen

Heterogeneity amongst dendritic cell (DC) subsets leads to a spectrum of immune response capacity against pathogens. Several DC subsets in spleen have been described which differ in terms of phenotype and function. We have previously reported a distinct population of CD11c(lo)CD11b(hi)MHC-II(-)CD8(-) dendritic-like "L-DC" in murine spleen, which can also be generated in splenic stromal longterm cultures. Here, the ontogeny of L-DC development in perinatal mice has been compared with other known splenic DC subsets. Flow cytometric analysis has revealed the presence of L-DC at embryonic age (E)18.5 spleen, while plasmacytoid (p)DC and conventional (c)DC appear at 2 and 4 days following birth. Co-cultures of E18.5 spleen above splenic stroma also showed production of only L-DC, while spleen cells from D0 through D5 neonates showed production of both L-DC and cDC-like cells. Addition of an M-CSFR inhibitor to co-cultures revealed that while the development of cDC-like cells depended on M-CSF, many L-DC developed independently of M-CSF. Furthermore, purified hematopoietic stem cells (HSC) and multipotential progenitors (MPP) isolated from neonatal D1 spleen are capable of developing into L-DC in co-cultures. These studies reveal a lineage of dendritic-like cells developing in the spleen microenvironment, and which appear to arise from endogenous progenitors laid down in spleen during embryogenesis.This work was supported by project grant #585443 to H.C.O. from the National Health and Medical Research Council of Australia. S.P. was supported by a graduate scholarship from the Royal Thai Government.

Qualitative differences in the mindsets associated with dual nature of normative commitment

This study aims to o uncover how employees' normative commitment (sense of obligation) to their organization is experienced in terms of dual normative commitment (moral imperative or indebted obligation) and to describe the potential for different mindsets arising through the dynamic combination of the various components in the commitment profile. Semi-structured interviews were conducted with 16 participants. The interviews were designed to identify the respondents' perceptions of obligation to their organisation, and their underlying motivational mindset associating with dual nature of normative commitment The interview findings for the affective-normative commitment dominant and the continuance commitment dominant participants were consistent with normative commitment experienced as either moral imperative or an indebted obligation, depending on the relative levels of affective and continuance commitment. All participants irrespective of their commitment profile noted that they had commitment to multiple foci, however, the alignment between commitment to these various foci differed by commitment profile. The qualitative differences among the commitment profiles indicated that the interaction of the commitment components is more complex than current commitment profile propositions suggest and that further theory development beyond the mindsets associated with continuance commitment and affective-normative commitment dominant profiles is required

Distinct progenitor origin distinguishes a lineage of dendritic-like cells in spleen

The dendritic cell (DC) compartment comprises subsets of cells with distinct phenotypes. Previously this lab reported methodology for hematopoiesis of dendritic-like cells in vitro dependent on a murine splenic stromal cell line (5G3). Co-cultures of lineage-depleted bone marrow (Lin(-) BM) over 5G3 continuously produced a distinct population of dendritic-like "L-DC" for up to 35 days. Here the progenitor of L-DC is investigated in relation to known BM-derived hematopoietic progenitors. It is shown here that L-DC-like cells also derive from the CD150(+)Flt3(-) long-term reconstituting-hematopoietic stem cells (HSC), and also from the Flt3(+) multipotential progenitor subset in BM. Lin(-) BM co-cultures also produce a transient population of cells resembling conventional (c) DC. Production of cDC-like cells is shown here to be transient and M-CSF dependent, and also appears following co-culture of described common dendritic progenitors or monocyte dendritic progenitors over 5G3. BM cells from C57BL/6-flt3L(tm1lmx) and C57BL/6-Csf2(tm1Ard) mice which lack cDC precursors and monocytes, are shown here to contain L-DC progenitors which can seed 5G3 co-cultures. L-DC are functionally distinct cells, in that they arise independently of M-CSF, and by direct differentiation from HSC.This work was supported by project grant #585443 to Helen Christine O’Neill from the National Health and Medical Research Council of Australia. Sawang Petvises was supported by a graduate scholarship from the Royal Thai Government

How small business advisory program delivery methods (collective learning, tailored, and practice-based approaches) affect learning and innovation

Past studies relate small business advisory program effectiveness to advisory characteristics such as advisory intensity and scope. We contribute to existing literature by seeking to identify the impact of different advisory program methods of delivery on learning and subsequent firm innovation behavior. Our research is based on a survey of 257 Australian firms completing small business advisory programs in the three years preceding the research. We explore the range of small business advisory program delivery methods in which our surveyed firms participated and, with reference to the literature on organizational learning and innovation, we analyze predictors of firms' learning ability and innovativeness based on the identified delivery methods. First, we found that business advisory programs that involved high levels of collective learning and tailored approaches enhanced firms' perceptions of their learning of critical skills or capabilities. We also found that small business advisory programs that were delivered by using practice-based approaches enhanced firms' subsequent organizational innovation. We verified this finding by testing whether firms that have participated in small business advisory services subsequently demonstrate improved behavior in terms of organizational innovativeness, when compared with matched firms that have not participated in an advisory program

Increasing learners' satisfaction/intention to adopt more e-learning

Purpose: E-learning is an organisationally risky investment given the cost and poor levels of adoption by users. In order to gain a better understanding of this problem, a study was conducted into the use of e-learning in a rail organisation. Design/methodology/approach: Using an online survey, employees of a rail-sector organisation were questioned about their use and likelihood of adoption of e-learning. This study explores the factors that affect the way in which learners experience and perceive such systems. Using statistical analysis, twelve hypotheses are tested and explored. Relationships between learning satisfaction, intention to adopt and the characteristics of e-learning systems were established. Findings: The study found that e-learning characteristics can buffer the relationship between learner characteristics and intention to adopt further e-learning in the future. Further, we found that high levels of support can compensate individuals who are low in technological efficacy to adopt e-learning. Research limitations/implications: The cross-sectional design of the study and its focus on measuring intention to adopt as opposed to actual adoption are both limitations. Future research using longitudinal design and research employing a time lag design measuring actual adoption as well as intention are recommended. Practical implications: From a practical perspective, organizations can focus on the actual content and authenticity of the learning experience delivered by the e-learning system to significantly impact how employees will perceive and use e-learning in the future. Low technological efficacy individuals tend not to adopt new technology. Instead of changing individuals’ personalities, organizations can implement supportive policies and practices which would lead to higher e-learning adoption rate among low efficacy individuals. Originality/value: The study integrates technology adoption and learning literatures in developing enablers for e-learning in organizations. Further, this study collects data from rail employees, and therefore the findings are practical to an industry