How Dopamine Enables Learning from Aversion.

Dopamine is heavily studied for its role in reward learning, but it is becoming increasingly appreciated that dopamine can also enable learning from aversion. Dopamine neurons modulate their firing and neurotransmitter release patterns in response to aversive outcomes. However, there is considerable heterogeneity in the timing and directionality of the modulation.

Gynecologic health care for LGBTQIA+ people.

Gender relations are a set of socially determined norms and rules that assign values, characteristics, and expectations to individuals based on their biological sex. These aspects also influence the clinician-patient relationship, since it has been for a long time based on cisheteronormativity. However, this attitude alienated the LGBTQIA+ community from health services.

T-FINDER: A highly sensitive, pan-HLA platform for functional T cell receptor and ligand discovery.

Effective, unbiased, high-throughput methods to functionally identify both class II and class I HLA-presented T cell epitopes and their cognate T cell receptors (TCRs) are essential for and prerequisite to diagnostic and therapeutic applications, yet remain underdeveloped. Here, we present T-FINDER [T cell Functional Identification and (Neo)-antigen Discovery of Epitopes and Receptors], a system to rapidly deconvolute CD4 and CD8 TCRs and targets physiologically processed and presented by an individual's unmanipulated, complete human leukocyte antigen (HLA) haplotype. Combining a highly sensitive TCR signaling reporter with an antigen processing system to overcome previously undescribed limitations to target expression, T-FINDER both robustly identifies unknown peptide:HLA ligands from antigen libraries and rapidly screens and functionally validates the specificity of large TCR libraries against known or predicted targets.

H3K27M neoepitope vaccination in diffuse midline glioma induces B and T cell responses across diverse HLA loci of a recovered patient.

H3K27M, a driver mutation with T and B cell neoepitope characteristics, defines an aggressive subtype of diffuse glioma with poor survival. We functionally dissect the immune response of one patient treated with an H3K27M peptide vaccine who subsequently entered complete remission. The vaccine robustly expanded class II human leukocyte antigen (HLA)-restricted peripheral H3K27M-specific T cells.