9 research outputs found

    A developmental approach to diversifying neuroscience through effective mentorship practices: perspectives on cross-identity mentorship and a critical call to action.

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    Many early-career neuroscientists with diverse identities may not have mentors who are more advanced in the neuroscience pipeline and have a congruent identity due to historic biases, laws, and policies impacting access to education. Cross-identity mentoring relationships pose challenges and power imbalances that impact the retention of diverse early career neuroscientists, but also hold the potential for a mutually enriching and collaborative relationship that fosters the mentee\u27s success. Additionally, the barriers faced by diverse mentees and their mentorship needs may evolve with career progression and require developmental considerations. This article provides perspectives on factors that impact cross-identity mentorship from individuals participating in Diversifying the Community of Neuroscience (CNS)-a longitudinal, National Institute of Neurological Disorders and Stroke (NINDS) R25 neuroscience mentorship program developed to increase diversity in the neurosciences. Participants in Diversifying CNS were comprised of 14 graduate students, postdoctoral fellows, and early career faculty who completed an online qualitative survey on cross-identity mentorship practices that impact their experience in neuroscience fields. Qualitative survey data were analyzed using inductive thematic analysis and resulted in four themes across career levels: (1) approach to mentorship and interpersonal dynamics, (2) allyship and management of power imbalance, (3) academic sponsorship, and (4) institutional barriers impacting navigation of academia. These themes, along with identified mentorship needs by developmental stage, provide insights mentors can use to better support the success of their mentees with diverse intersectional identities. As highlighted in our discussion, a mentor\u27s awareness of systemic barriers along with active allyship are foundational for their role

    Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis

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    © The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.This work was supported by the Leona M. and Harry B. Helmsley Charitable trust (SHARE), the Digestive Diseases Research Core Center C-IID P30 DK42086 at the University of Chicago, the PSC Partners Seeking a Cure Canada and the Sczholtz Family Foundation. K.R.M. is supported by grant no. NS124187. S.C.S. is supported by an American Gastroenterological Association Research Scholar Award, Veterans Affairs Career Development Award (no. ICX002027A01) and the San Diego Digestive Diseases Research Center (no. P30 DK120515). C.Q. is supported by the BBSRC Core Strategic Programme Grant (BB/CSP1720/1, BBS/E/T/000PR9818 and BBS/E/T/000PR9817). I.H.J. is supported by a Rosalind Franklin Fellowship from the University of Groningen and a Netherlands Organization for Scientific Research VIDI grant no. 016.171.047. D.G.S. is supported by grant no. F30DK121470.info:eu-repo/semantics/publishedVersio

    Dietary polyphenols drive dose-dependent behavioral and molecular alterations to repeated morphine

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    Abstract Opioid Use Disorder (OUD) is associated with tremendous morbidity and mortality. Despite this burden, current pharmacotherapies for OUD are ineffective or intolerable for many patients. As such, interventions aimed at promoting resilience against OUD are of immense clinical interest. Treatment with a Bioactive Dietary Polyphenol Preparation (BDPP) promotes resilience and adaptive neuroplasticity in multiple models of neuropsychiatric disease. Here, we assessed effects of BDPP treatment on behavioral and molecular responses to repeated morphine treatment in male mice. BDPP pre-treatment alters responses for both locomotor sensitization and conditioned place preference. Most notably, polyphenol treatment consistently reduced formation of preference at low dose (5 mg/kg) morphine but enhanced it at high dose (15 mg/kg). In parallel, we performed transcriptomic profiling of the nucleus accumbens, which again showed a dose × polyphenol interaction. We also profiled microbiome composition and function, as polyphenols are metabolized by the microbiome and can act as prebiotics. The profile revealed polyphenol treatment markedly altered microbiome composition and function. Finally, we investigated involvement of the SIRT1 deacetylase, and the role of polyphenol metabolites in behavioral responses. These results demonstrate polyphenols have robust dose-dependent effects on behavioral and physiological responses to morphine and lay the foundation for future translational work
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