The Impact of HLA-DQαβ Heterodimer Mismatch on Living Donor Kidney Allograft Outcomes.

Background: HLA-DQ mismatch has been identified as a predictor of de novo donor-specific HLA antibody formation and antibody-mediated rejection. There are insufficient data to guide the incorporation of DQ mismatch into organ allocation decisions.

Methods: We used a retrospective longitudinal cohort of adult living donor kidney transplant recipients from 11 centers across the United States for whom high-resolution class II typing was available.

CDK9 Inhibition by Dinaciclib Is a Therapeutic Vulnerability in Epithelioid Hemangioendothelioma.

Purpose: There are no effective treatment options for patients with aggressive epithelioid hemangioendothelioma (EHE) driven by the TAZ-CAMTA1 (TC) fusion gene. Here, we aimed to understand the regulation of TC using pharmacologic tools and identify vulnerabilities that can potentially be exploited for the treatment of EHE.

Experimental Design: TC is a transcriptional coregulator; we hypothesized that compounds that reduce TC nuclear levels, either through translocation of TC to the cytoplasm, or through degradation, would render TC less oncogenic.

Loss of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma.

Purpose: Epithelioid hemangioendothelioma (EHE) is a vascular sarcoma caused by the WWTR1(TAZ)-CAMTA1 (TC) gene fusion. This fusion gene has been observed in almost all reported EHE cases and functions as a constitutively activated TAZ. Sequencing of human tumors has, however, identified additional secondary mutations in approximately 50% of EHE, most commonly the loss of tumor suppressor CDKN2A.

The TAZ-CAMTA1 Fusion Protein Promotes Tumorigenesis via Connective Tissue Growth Factor and Ras-MAPK Signaling in Epithelioid Hemangioendothelioma.

Purpose: A consistent genetic alteration in vascular cancer epithelioid hemangioendothelioma (EHE) is the t(1;3)(p36;q25) chromosomal translocation, which generates a WWTR1(TAZ)-CAMTA1 (TC) fusion gene. TC is a transcriptional coactivator that drives EHE. Here, we aimed to identify the TC transcriptional targets and signaling mechanisms that underlie EHE tumorigenesis.

Evolutionary change in the construction of the nursery environment when parents are prevented from caring for their young directly.

Parental care can be partitioned into traits that involve direct engagement with offspring and traits that are expressed as an extended phenotype and influence the developmental environment, such as constructing a nursery. Here, we use experimental evolution to test whether parents can evolve modifications in nursery construction when they are experimentally prevented from supplying care directly to offspring. We exposed replicate experimental populations of burying beetles () to different regimes of posthatching care by allowing larvae to develop in the presence (Full Care) or absence of parents (No Care).