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

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

The Behavioral Assessment Screening Tool for Mobile Health (BASTmHealth): Development and Compliance in Two Weeks of Daily Reporting in Chronic Traumatic Brain Injury

Objectives: To develop and evaluate the feasibility of a short form of the Behavioral Assessment Screening Tool (BASTmHealth) for high frequency in situ self-reported assessment of neurobehavioral symptoms using mobile health technology for community-dwelling adults with traumatic brain injury (TBI). Design: Prospective, repeated measures study of mHealth assessment of self-reported neurobehavioral symptoms in adults with and without a lifetime history of TBI over a two-week period. Setting: Community Participants: Community-dwelling adults with (n=52) and without (n=12) a lifetime TBI history consented to the study. Interventions: Not applicable Main Outcome Measures: BASTmHealth subscales (2-items each): Negative Affect, Fatigue, Executive Function, Substance Abuse, Impulsivity; Feasibility measured via compliance (assessments assigned/assessments completed) and participant-reported usability. Results: We developed the 10-item BASTmHealth as a screener for high frequency in situ self-reported assessment of neurobehavioral symptoms leveraging mHealth. Compliance for two-weeks of BASTmHealth supports its feasibility. Fifty-six of 64 participants (87.5%) who completed baseline assessments completed the two-weeks of daily assessments; all 8 participants who did not complete EMA had a history of TBI. Overall compliance was 81.4% (496 completed of 609 assigned assessments) among all 52 participants with TBI and 96.7% (494 completed of 511 assigned assessments) among the 44 who completed any daily measures, compared to 91.8% (135 completed of 147 assigned assessments) among those with no TBI history. Participants thought the daily surveys were easy to understand and complete and the number of prompts were reasonable. Conclusions: Conducting daily high frequency in situ self-reported assessment of neurobehavioral symptoms using the BASTmHealth is feasible among individuals with and without a lifetime history of TBI. Developing and evaluating self-reported assessments for community-based assessment is a critical step towards expanding remote clinical monitoring systems to improve post-TBI outcomes

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1−/− mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1−/− mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection

Search for short baseline nu(e) disappearance with the T2K near detector

8 pages, 6 figures, submitted to PRD rapid communication8 pages, 6 figures, submitted to PRD rapid communicationWe thank the J-PARC staff for superb accelerator performance and the CERN NA61 collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC and CFI, Canada; Commissariat `a l’Energie Atomique and Centre National de la Recherche Scientifique–Institut National de Physique Nucle´aire et de Physique des Particules, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; Russian Science Foundation, RFBR and Ministry of Education and Science, Russia; MINECO and European Regional Development Fund, Spain; Swiss National Science Foundation and State Secretariat for Education, Research and Innovation, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK. In addition participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; DOE Early Career program, USA

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

Predictors of Dropout in a Digital Intervention for the Prevention and Treatment of Depression in Patients With Chronic Back Pain : Secondary Analysis of Two Randomized Controlled Trials

Peer reviewe