Duality in the Th17-Treg developmental decision

Each of the effector CD4 T-cell lineages - Th1, Th2, and the more recently identified Th17 - arises from pluripotent naïve precursors whose developmental fate is largely controlled by cytokines that act in concert with antigenic signals. Remarkably, development of the Th17 lineage has been linked to that of regulatory T cells, which obviate or downregulate Th17 responses to preserve immune homeostasis, through a shared requirement for the cytokine transforming growth factor-beta. Several new studies offer insights into the mechanism whereby the precursors of these subsets are directed into distinct lineages

Wiley Journal Package: UNL Download Activity by Subject

Because the field of librarianship has been reconsidering its relationship to commercial academic publishers and their \u27Big Deal\u27 journal packages, the authors decided to review the University of Nebraska-Lincoln\u27s usage of Wiley\u27s package. In this report, the authors looked into whether UNL\u27s downloads by subject were such that subscribing to a number of hypothetical smaller, subject-specific packages, rather than to the entire Wiley package, might be a viable strategy

Efficient adenovirus-mediated gene transfer into primary T cells and thymocytes in a new coxsackie/adenovirus receptor transgenic model

BACKGROUND: Gene transfer studies in primary T cells have suffered from the limitations of conventional viral transduction or transfection techniques. Replication-defective adenoviral vectors are an attractive alternative for gene delivery. However, naive lymphocytes are not readily susceptible to infection with adenoviruses due to insufficient expression of the coxsackie/adenovirus receptor. RESULTS: To render T cells susceptible to adenoviral gene transfer, we have developed three new murine transgenic lines in which expression of the human coxsackie/adenovirus receptor (hCAR) with a truncated cytoplasmic domain (hCARΔcyt) is limited to thymocytes and lymphocytes under direction of a human CD2 mini-gene. hCARΔcyt.CD2 transgenic mice were crossed with DO11.10 T cell receptor transgenic mice (DO11.hCARΔcyt) to allow developmental studies in a defined, clonal T cell population. Expression of hCARΔcyt enabled adenoviral transduction of resting primary CD4(+) T cells, differentiated effector T cells and thymocytes from DO11.hCARΔcyt with high efficiency. Expression of hCARΔcyt transgene did not perturb T cell development in these mice and adenoviral transduction of DO11.hCARΔcyt T cells did not alter their activation status, functional responses or differentiative potential. Adoptive transfer of the transduced T cells into normal recipients did not modify their physiologic localization. CONCLUSION: The DO11.hCARΔcyt transgenic model thus allows efficient gene transfer in primary T cell populations and will be valuable for novel studies of T cell activation and differentiation

Trace element distribution and arsenic speciation in toenails as affected by external contamination and evaluation of a cleaning protocol

Open Access via the ACS agreement This research was performed on the XFM beamline at the Australian Synchrotron, part of ANSTO. Special thanks to Prof Dr Rajiv Chowdhury (University of Florida, Miami, USA) for the financial and academic support as scientific manager of the BRAVE study while at the University of Cambridge (Cambridge, UK). We gratefully acknowledge the contributions of all BRAVE study participants, the scientific staff of the collaborating centre icddr,b and the recruitment centre NICVD in Bangladesh. Epidemiological fieldwork in BRAVE has been supported by grants to the coordination centre for BRAVE at the British Heart Foundation (BHF) Cardiovascular Epidemiology Unit (CEU) at the University of Cambridge. The CEU is underpinned by programme grants from the: BHF (RG/13/13/30194; RG/18/13/33946), UK Medical Research Council (MR/L003120/1) and NIHR Cambridge Biomedical Research Centre (BRC-1215-20014; NIHR203312) [*]. *The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.Peer reviewe

Children\u27s Perceptions of Parent-Child Relationships: A Narrative, Inductive Approach

Background: Narrative methods can allow researchers to gather rich data from children regarding their perceptions of their relationship with parents that may not otherwise be captured using tasks, questionnaires, or structured interviews; however, existing coding systems have been established with samples that are largely White and middle class. The current study sought to establish child-inspired codes that would better reflect the sample. Methods: Children aged 5-12 years (M=8.82, 48.9% female) and their caregivers were recruited from high-poverty urban US areas. All participants identified as Black or African American. Children were audiotaped while speaking, uninterrupted, for three minutes about their relationship with their primary caregiver (TMSS; Marshall et al., 1990). A team of five researchers - diverse in race, ethnicity, and background - established a codebook using in-vivo methods, dually coded N=51 transcripts via thematic analysis, and analyzed codes for emergent themes (Braun & Clarke, 2006). Results: Coders identified N=671 codes from the transcripts, of which 332 (49.5%) were unique codeable units. Five themes emerged from the data: interactions, feelings about caregiver, emotional closeness, reciprocity, and insight. Conclusions: The use of open-ended speech sampling coupled with qualitative coding allowed cataloging of Black children’s own perceptions of the parent-child relationship. Children emphasized time spent together, mutual understanding, & reciprocity. Many children also showed insight into parents’ perspectives and motivations, including financial awareness. Previous work indicates this dyadic reciprocity may be one way families protect themselves against the negative consequences of financial difficulties (Wilhoit et al., 2021). References: Braun, V., & Clarke, V. (2006). Using thematic analysis in psychology. Qualitative Research in Psychology, 3, 77–101. https://doi.org/10.1191/1478088706qp063oa Marshall, V.G., Longwell, L., Goldstein, M.J., & Swanson, J.M. (1990). Family factors associated with aggressive symptomatology in boys with Attention Deficit Hyperactivity Disorder: A research note. J. Child Psychol. Psychiat., 31(4), 629-636. https://doi.org/10.1111/j.1469-7610.1990.tb00802.x Wilhoit, S.A., Trentacosta, C.J., Beeghly, M., Boeve, J.L., Lewis, T.L. and Thomason, M.E. (2021). Household chaos and early childhood behavior problems: The moderating role of mother–child reciprocity in lower-income families. Fam Relat, 70, 1040-1054. https://doi.org/10.1111/fare.12560https://scholarscompass.vcu.edu/gradposters/1174/thumbnail.jp

Notch Simultaneously Orchestrates Multiple Helper T Cell Programs Independently of Cytokine Signals

SummaryTwo models are proposed to explain Notch function during helper T (Th) cell differentiation. One argues that Notch instructs one Th cell fate over the other, whereas the other posits that Notch function is dictated by cytokines. Here we provide a detailed mechanistic study investigating the role of Notch in orchestrating Th cell differentiation. Notch neither instructed Th cell differentiation nor did cytokines direct Notch activity, but instead, Notch simultaneously regulated the Th1, Th2, and Th17 cell genetic programs independently of cytokine signals. In addition to regulating these programs in both polarized and nonpolarized Th cells, we identified Ifng as a direct Notch target. Notch bound the Ifng CNS-22 enhancer, where it synergized with Tbet at the promoter. Thus, Notch acts as an unbiased amplifier of Th cell differentiation. Our data provide a paradigm for Notch in hematopoiesis, with Notch simultaneously orchestrating multiple lineage programs, rather than restricting alternate outcomes