Stepwise development of thymic microenvironments in vivo is regulated by thymocyte subsets

T-cell development is under the tight control of thymic microenvironments. Conversely, the integrity of thymic microenvironments depends on the physical presence of developing thymocytes, a phenomenon designated as 'thymic crosstalk'. We now show, using three types of immunodeficient mice, i.e. CD3(epsilon) transgenic mice, RAG(null) mice and RAG(null)-bone-marrow-transplanted CD3(epsilon) transgenic mice, that the control point in lymphoid development where triple negative (CD3(-),CD4(-),CD8(-)) thymocytes progress from CD44(+)CD25(-) towards CD44(-)CD25(+), influences the development of epithelial cells, critically inducing the extra, third dimension in the organization of the epithelial cells in the cortex. This tertiary configuration of the thymic epithelium is a typical feature for the thymus, enabling lymphostromal interaction during T-cell development. Crosstalk signals at this control point also induce the formation of thymic nurse cells. Moreover, our data indicate that establishment of a thymic cortex is a prerequisite for the development of the thymic medulla. Thus, differentiating thymocytes regulate the morphogenesis of thymic microenvironments in a stepwise fashion

The effect of an invasive bryozoan on community diversity and structure varies across two locations

Abstract Foundation species and invasive species strongly influence community diversity and structure, but typically in different ways. However, when widespread invasive species provide novel habitat within a community, their net effect may depend on both the environment and community composition. Fouling communities in northern and southern California harbors were surveyed to determine whether there was variation between two locations in the percent cover of an invasive bryozoan, Watersipora subtorquata (d'Orbigny, 1852), and its relationship to community diversity and composition in these two environments. Diversity significantly differed between locations and had a location-dependent association with W. subtorquata abundance. Communities were significantly dissimilar between locations, and W. subtorquata abundance had the highest percent contribution to community dissimilarity when compared to other species in the community. These results suggest that invasive species may have both facilitative and inhibitive relationships with species in a community, but that the net balance of these interactions depends on both the environmental and community context

Predicting Symptoms of Depression and Anxiety Using Smartphone and Wearable Data

Background: Depression and anxiety are leading causes of disability worldwide but often remain undetected and untreated. Smartphone and wearable devices may offer a unique source of data to detect moment by moment changes in risk factors associated with mental disorders that overcome many of the limitations of traditional screening methods. Objective: The current study aimed to explore the extent to which data from smartphone and wearable devices could predict symptoms of depression and anxiety. Methods: A total of N = 60 adults (ages 24-68) who owned an Apple iPhone and Oura Ring were recruited online over a 2-week period. At the beginning of the study, participants installed the Delphi data acquisition app on their smartphone. The app continuously monitored participants' location (using GPS) and smartphone usage behavior (total usage time and frequency of use). The Oura Ring provided measures related to activity (step count and metabolic equivalent for task), sleep (total sleep time, sleep onset latency, wake after sleep onset and time in bed) and heart rate variability (HRV). In addition, participants were prompted to report their daily mood (valence and arousal). Participants completed self-reported assessments of depression, anxiety and stress (DASS-21) at baseline, midpoint and the end of the study. Results: Multilevel models demonstrated a significant negative association between the variability of locations visited and symptoms of depression (beta = -0.21, p = 0.037) and significant positive associations between total sleep time and depression (beta = 0.24, p = 0.023), time in bed and depression (beta = 0.26, p = 0.020), wake after sleep onset and anxiety (beta = 0.23, p = 0.035) and HRV and anxiety (beta = 0.26, p = 0.035). A combined model of smartphone and wearable features and self-reported mood provided the strongest prediction of depression. Conclusion: The current findings demonstrate that wearable devices may provide valuable sources of data in predicting symptoms of depression and anxiety, most notably data related to common measures of sleep.Peer reviewe

The Checkpoint Regulator SLAMF3 Preferentially Prevents Expansion of Auto-Reactive B Cells Generated by Graft-vs.-Host Disease

Absence of the mouse cell surface receptor SLAMF3 in SLAMF3-/- mice suggested that this receptor negatively regulates B cell homeostasis by modulating activation thresholds of B cell subsets. Here, we examine whether anti-SLAMF3 affects both B and T cell subsets during immune responses to haptenated ovalbumin [NP-OVA] and in the setting of chronic graft vs. host disease (cGVHD) induced by transferring B6.C-H2 bm12/KhEg (bm12) CD4+ T cells into B6 WT mice. We find that administering αSLAMF3 to NP-OVA immunized B6 mice primarily impairs antibody responses and Germinal center B cell [GC B] numbers, whilst CXCR5+, PD-1+, and ICOS+ T follicular helper (TFH) cells are not significantly affected. By contrast, administering αSLAMF3 markedly enhanced autoantibody production upon induction of cGVHD by the transfer of bm12 CD4+ T cells into B6 recipients. Surprisingly, αSLAMF3 accelerated both the differentiation of GC B and donor-derived TFH cells initiated by cGVHD. The latter appeared to be induced by decreased numbers of donor-derived Treg and T follicular regulatory (TFR) cells. Collectively, these data show that control of anti-SLAMF3-induced signaling is requisite to prevent autoantibody responses during cGVHD, but reduces responses to foreign antigens

Re-municipalization of public services: trend or hype?

Re-municipalization is part of a broader set of reverse privatization reforms. We argue the term re-municipalization lacks conceptual clarity and often confuses municipal level reversals from national ones, new service delivery from reversals, and mixed market positions (such as corporatization) from full public control. This conceptual confusion makes measurement of re-municipalization difficult. While more case studies are being discovered, studies based on quantitative time series do not show re-municipalization as an increasing trend. Much case study based research argues re-municipalization is politically transformative, but quantitative research generally finds re-municipalization to be part of a pragmatic market management process, a position confirmed by the papers in this special issue

US chiropractors' attitudes, skills and use of evidence-based practice: A cross-sectional national survey

Background: Evidence based practice (EBP) is being increasingly utilized by health care professionals as a means of improving the quality of health care. The introduction of EBP principles into the chiropractic profession is a relatively recent phenomenon. There is currently a lack of information about the EBP literacy level of US chiropractors and the barriers/facilitators to the use of EBP in the chiropractic profession. Methods: A nationwide EBP survey of US chiropractors was administered online (Nov 2012-Mar 2013) utilizing a validated self-report instrument (EBASE) in which three sub-scores are reported: attitudes, skills and use. Means, medians, and frequency distributions for each of the sub-scores were generated. Descriptive statistics were used to analyze the demographic characteristics of the sample. Means and proportions were calculated for all of the responses to each of the questions in the survey. Results: A total of 1,314 US chiropractors completed the EBASE survey; the sample appeared to be representative of the US chiropractic profession. Respondents were predominantly white (94.3%), male (75%), 47 (+/- 11.6) years of age, and in practice for more than 10 years (60%). EBASE sub-score means (possible ranges) were: attitudes, 31.4 (8-40); skills, 44.3 (13-65); and use, 10.3 (0-24). Survey participants generally held favorable attitudes toward EBP, but reported less use of EBP. A minority of participants indicated that EBP coursework (17%) and critical thinking (29%) were a major part of their chiropractic education. The most commonly reported barrier to the use of EBP was "lack of time". Almost 90% of the sample indicated that they were interested in improving their EBP skills. Conclusion: American chiropractors appear similar to chiropractors in other countries, and other health professionals regarding their favorable attitudes towards EBP, while expressing barriers related to EBP skills such as research relevance and lack of time. This suggests that the design of future EBP educational interventions should capitalize on the growing body of EBP implementation research developing in other health disciplines. This will likely include broadening the approach beyond a sole focus on EBP education, and taking a multilevel approach that also targets professional, organizational and health policy domains

SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer

The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6−/− recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell–related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy