Hair Follicle Melanogenesis Reflected in Hair Pigmentation as a Developmental Factor in Alopecia Areata

The mechanism of alopecia areata (AA) is not well-elucidated, and hair follicle melanogenesis pathways are implicated as possible sources for autoantigens. After a retrospective medical record review at a single tertiary medical center, the hair color of 112 AA patients were identified and compared to a control group of 104 androgenetic alopecia patients. There were no statistically significant differences in the natural hair color prevalence between the 2 groups (<i>p</i> = 0.164), and hair color was not a predictor of the alopecia type. Our results suggest hair pigmentation, determined by the eumelanin-to-pheomelanin ratio, is not a positive risk factor for AA development. We hope that our study will encourage multiple large-scale, collaborative, retrospective medical reviews to determine if our results are reproducible in diverse patient populations.

TCF-1 in CD8 T cells separates GVHD from GVL

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for hematological malignancy due to graft-versus-leukemia (GVL) effects, mediated by alloreactive donor T cells. However, these same donor cells cause graft-versus-host disease (GVHD), a life-threatening complication. During GVHD, donor T cells proliferate, migrate, and produce cytokines, leading to damage of healthy host tissues. Separating the linked processes of GVHD and GVL is critical to improving outcomes. Here we show that TCF-1, a major T cell developmental factor, plays a role in regulation of these processes. Using a mouse model of allo-HSCT leading to GVHD, we found that conditional loss of TCF-1 in mature CD8 T cells separates GVHD from GVL, providing an optimal clinical phenotype. This occurred due to changes in cytokine production, proliferation, cell survival, chemokine receptor expression, and gene expression. Thus, modulation of TCF-1 signaling reduces GVHD severity and persistence, but maintains GVL effects, and could be useful for allo-HSCT or other T cell-mediated disorders. Furthermore, here and in our companion manuscript we show that regulation of mature, alloactivated T cells by TCF-1 differs between CD4 and CD8 T cells, suggesting that TCF-1 is critical for regulation of mature alloactivated T cells, with unique programs in each subset.

A Conceptual Analysis of Autistic Masking: Understanding the Narrative of Stigma and the Illusion of Choice

Research into autistic masking has recently started to gain traction, showing that masking is related to late/missed diagnosis, and a selection of negative outcomes including burnout and suicidality in autistic people. Though masking is described as a social strategy, the application of social theory to understanding masking is sparse. In this analysis we review literature so far in light of the historical deficit focussed narrative of autism and make suggestions for how we can use social psychological theory to better understand what masking is. We discuss the role of stigma on identity expression, and how social theory can be applied to understanding which aspects of contextual identity shifts are harmful to autistic people. We also discuss issues around a gendered narrative of masking, including the exclusion of non-binary autistic people, and those whose autistic characteristics do not fit within a binary narrative. Finally, we make suggestions for future research, including the use of a multidimensional conceptualisation of masking that takes into account the role of internal and external aspects of masking, in interaction with the role of time as a developmental factor.

Ryzyko i ochrona w środowisku rówieśniczym. Czyli o znaczeniu relacji koleżeńskich w życiu nastolatków

This article is devoted to the issue of peer relations, which are an important developmental factor and affect the welfare of adolescent boys and girls. According to many authors, relationships with peers during adolescence carry not only risk as a consequence of peer pressure to undertake unfavourable behaviors, but may also potentially contribute to well-being and life success. The analysis of available research results helped to distinguish two main risk factors resulting from peer relations, which include: mutual influence and modelling of disadaptive behaviours and rejection by peers. The protective factors, in turn, included: mutual influence and modelling of adaptive behaviours, a sense of happiness resulting from peer relations and compensating for other difficulties through peer relations.

Daam2 Driven Degradation of VHL Promotes Gliomagenesis

Von Hippel-Landau (VHL) protein is a potent tumor suppressor regulating numerous pathways that drive cancer, but mutations in VHL are restricted to limited subsets of malignancies. Here we identified a novel mechanism for VHL suppression in tumors that do not have inactivating mutations. Using developmental processes to uncover new pathways contributing to tumorigenesis, we found that Daam2 promotes glioma formation. Protein expression screening identified an inverse correlation between Daam2 and VHL expression across a host of cancers, including glioma. Thesein silicoinsights guided corroborating functional studies, which revealed that Daam2 promotes tumorigenesis by suppressing VHL expression. Furthermore, biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. Together, these studies are the first to define an upstream mechanism regulating VHL suppression in cancer and describe the role of Daam2 in tumorigenesis.Statement of SignificanceWe found that the glial developmental factor Daam2 promotes glioma tumorigenesis by suppressing VHL expression. Our studies show, for the first time, a regulatory mechanism that operates upstream of VHL in cancer and provides an explanation for how VHL expression is extinguished in tumors that do not have inactivating mutations.