Expression and function of the atypical chemokine receptor CCRL1 in the thymus

Thymus colonisation and thymocyte positioning are mediated by interactions involving CCR7 and CCR9 and their respective ligands CCL19/CCL21 and CCL25. These chemokines also interact with the atypical receptor CCRL1, which is expressed in the thymus and has recently been reported to play an important role in normal abT-cell development. Our study has mapped CCRL1 expression within the adult and embryonic thymus, and shows that CCRL1 is expressed within the thymic cortex, at the subcapsular zone, and surrounding vessels at the corticomedullary junction. We have used flow cytometry to show CCRL1 expression predominantly by cortical thymic epithelial cells, but also by a small population of medullary thymic epithelial cells and by a subset of mesenchymal cells. We show, using CCRL1 deficient mice, that CCRL1 suppresses thymocyte progenitor entry into the thymus, and influences the intrathymic positioning of double negative thymocytes. Nevertheless, we have shown that CCRL1-/- mice have no major perturbations in T- cell populations at different stages of thymic differentiation and development. Overall, this study characterises the expression of CCRL1 in key thymic microenvironments, but argues against a major role for CCRL1 in normal thymus development and function

The Meaning and Motivation of Children Participating in Animal-Assisted Therapy: A Pilot Study

Background: Despite claims that animal-assisted therapy is beneficial, there is limited empirical evidence supporting this. Current literature supports the physical, emotional, and psychological benefits an animal can provide, but few studies have explored the outcomes of incorporating an animal into skilled treatment facilitated by a healthcare professional. This study seeks to explore the effects of animal-assisted therapy in outpatient pediatric occupational therapy practice. Purpose: The purpose of this research is to explore the meaningfulness and motivation animal-assisted therapy interventions provide for pediatric clients when compared with traditional occupational therapy treatment. Methods: Researchers utilized a within-participants repeated-measures design for this study. Children receiving animal-assisted therapy at a private practice occupational therapy clinic were videoed performing therapeutic activities with a licensed occupational therapist and trained dogs. The videos were gathered both with and without the animal present in the therapy session and coded to determine the meaningfulness and motivation of animal-assisted therapy versus traditional therapy without a dog. Results: Statistical analysis indicated that the childrens’ scores for initiating interactions with the therapist were significantly higher in the without dog condition than in the live dog condition. Furthermore, four out of the five children demonstrated increased on task/dog comments in the live dog condition than in the stuffed dog condition. The specific intervention activity performed influenced children’s engagement and enjoyment of animal-assisted therapy interventions. Conclusion: This pilot study provides preliminary evidence that animal-assisted therapy increases children’s enjoyment and engagement during therapeutic activities when a dog was present. Furthermore, the type of animal-assisted therapy activity performed may influence the children’s motivation to participate

Lymph Node Lymphatic Endothelial Cell Expansion and Contraction and the Programming of the Immune Response

Lymphatic endothelial cells (LECs) form the structure of the lymphatic vessels and the sinuses of the lymph nodes, positioning them to be key players in many different aspects of the immune response. Following an inflammatory stimulus, LECs produce chemokines that recruit immune cells to the lymph nodes. The recruitment of immune cells aids in the coordination of both LEC and lymph node expansion and contraction. More recent data has demonstrated that to coordinate LEC division and death, cell surface molecules, such as PD-L1 and interferon receptors, are required. During homeostasis, LECs use PD-L1 to maintain peripheral tolerance by presenting specific peripheral tissue antigens in order to eliminate tissue specific responses. LECs also have the capacity to acquire, present, and exchange foreign antigens following viral infection or immunization. Here we will review how lymph node LECs require immune cells to expand and contract in response to an immune stimulus, the factors involved and how direct LEC-immune cell interactions are important for programming immunity

Convergence in carnivorous pitcher plants reveals a mechanism for composite trait evolution.

Composite traits involve multiple components that, only when combined, gain a new synergistic function. Thus, how they evolve remains a puzzle. We combined field experiments, microscopy, chemical analyses, and laser Doppler vibrometry with comparative phylogenetic analyses to show that two carnivorous pitcher plant species independently evolved similar adaptations in three distinct traits to acquire a new, composite trapping mechanism. Comparative analyses suggest that this new trait arose convergently through "spontaneous coincidence" of the required trait combination, rather than directional selection in the component traits. Our results indicate a plausible mechanism for composite trait evolution and highlight the importance of stochastic phenotypic variation as a facilitator of evolutionary novelty

Timing, Duration, and Pathways of Harlequin Duck Migration to Pacific Molting and Wintering Areas

The core breeding range for Harlequin Ducks (Histrionicus histrionicus) in western North America extends from Alaska, and south through the Yukon, Northwest Territories, and British Columbia. Smaller breeding populations exist in southwestern Alberta, Washington, Oregon, Idaho, Wyoming, and Montana. Each state and province in these areas has identified the Harlequin Duck as a species of conservation priority, given its small and isolated populations, its specific nesting requirements, and changes in abundance or distribution. Conservation objectives for all areas have identified the importance of mapping migration routes that connect breeding sites to Pacific coast molting and wintering locations, as well as determining migration timing, duration, habitat use, and stopover sites. In spring 2016, we captured Harlequin Duck pairs on breeding streams and surgically implanted satellite transmitters in the males and attached geolocators to the leg bands of females. We marked 18 harlequin pairs (Alberta = 10 (minus one female), Montana = 5, Wyoming = 2, Washington = 1). Migration initiation dates varied by breeding areas and occurred from June 3 to July 10. Male migration lasted between 1-17 days and stopovers occurred approximately half-way to the coast and included rivers, mountain streams, and lakes. They arrived at their molting areas between June 5-July 24 and these areas ranged from southeast Alaska to northwestern Washington. The majority (71%) of harlequins departed molt locations to differing winter locations. Efforts will be made to retrieve the geolocators from females in spring 2017 to compare locations between males and females from different devices

Core competencies for pain management: results of an interprofessional consensus summit.

ObjectiveThe objective of this project was to develop core competencies in pain assessment and management for prelicensure health professional education. Such core pain competencies common to all prelicensure health professionals have not been previously reported.MethodsAn interprofessional executive committee led a consensus-building process to develop the core competencies. An in-depth literature review was conducted followed by engagement of an interprofessional Competency Advisory Committee to critique competencies through an iterative process. A 2-day summit was held so that consensus could be reached.ResultsThe consensus-derived competencies were categorized within four domains: multidimensional nature of pain, pain assessment and measurement, management of pain, and context of pain management. These domains address the fundamental concepts and complexity of pain; how pain is observed and assessed; collaborative approaches to treatment options; and application of competencies across the life span in the context of various settings, populations, and care team models. A set of values and guiding principles are embedded within each domain.ConclusionsThese competencies can serve as a foundation for developing, defining, and revising curricula and as a resource for the creation of learning activities across health professions designed to advance care that effectively responds to pain

Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.ISSN:2041-172

Diversity in medullary thymic epithelial cells controls the activity and availability of iNKT cells

The thymus supports multiple αβ T cell lineages that are functionally distinct, but mechanisms that control this multifaceted development are poorly understood. Here we examine medullary thymic epithelial cell (mTEC) heterogeneity and its influence on CD1d-restricted iNKT cells. We find three distinct mTEClow subsets distinguished by surface, intracellular and secreted molecules, and identify LTβR as a cell-autonomous controller of their development. Importantly, this mTEC heterogeneity enables the thymus to differentially control iNKT sublineages possessing distinct effector properties. mTEC expression of LTβR is essential for the development thymic tuft cells which regulate NKT2 via IL-25, while LTβR controls CD104+ CCL21+ mTEClow that are capable of IL-15-transpresentation for regulating NKT1 and NKT17. Finally, mTECs regulate both iNKT-mediated activation of thymic dendritic cells, and iNKT availability in extrathymic sites. In conclusion, mTEC specialization controls intrathymic iNKT cell development and function, and determines iNKT pool size in peripheral tissues