HLA class I antibody-activated endothelium promotes CD206+ M2-macrophage polarization and MMP9 secretion through TLR4 signaling and P-selectin in a model of antibody-mediated rejection and allograft vasculopathy.

HLA donor-specific antibodies (DSA) elicit alloimmune responses against the graft vasculature, leading to endothelial cell (EC) activation and monocyte infiltration during antibody-mediated rejection (AMR). AMR promotes chronic inflammation and remodeling, leading to thickening of the arterial intima termed transplant vasculopathy (TV) or cardiac allograft vasculopathy (CAV) in heart transplants. Intragraft-recipient macrophages serve as a diagnostic marker in AMR however, their polarization and function remain unclear.

De novo genome assemblies of two cryptodiran turtles with ZZ/ZW and XX/XY sex chromosomes provide insights into patterns of genome reshuffling and uncover novel 3D genome folding in amniotes.

Understanding the evolution of chromatin conformation among species is fundamental to elucidate the architecture and plasticity of genomes. Nonrandom interactions of linearly distant loci regulate gene function in species-specific patterns, affecting genome function, evolution, and, ultimately, speciation. Yet, data from nonmodel organisms are scarce.

The transcriptional repressor B cell lymphoma 6 regulates CXCR3 chemokine and human leukocyte antigen II expression in endothelial cells.

Interferon gamma (IFN-γ) induces an endothelial proimmunogenic phenotype through the JAK/STAT1 pathway, which can shape the activation of alloreactive leukocytes in transplant rejection. In immune cells, the DNA-binding protein B cell lymphoma 6 (BCL6) controls the transcription of inflammatory genes. This study tested if BCL6 modulates IFN-γ-induced gene expression in endothelial cells.

The effect of intergroup competition outcome on ingroup cooperation: insights from the male warrior hypothesis.

Introduction: The Male Warrior Hypothesis (MWH) proposes that sex-specific selective pressures have promoted male cooperation with the ingroup members to outcompete rival groups. However, intergroup conflicts do not occur in isolation and the outcomes of previous competitions may influence group cooperativeness. Since this phenomenon is not well understood, we aimed to shed light on the effect of previous competition outcome on later cooperative behavior under intergroup conflicts.

The role of exogenous testosterone and social environment on the expression of sociosexuality and status-seeking behaviors in young Chilean men.

Testosterone plays an important role as a social hormone. Current evidence suggests that testosterone is positively related to sociosexuality increasing the psychological attitudes toward investing in short-term versus long-term mating and promotes status-seeking behaviors both by dominance and prestige. In addition, the social environment may play an important role in the expression of mating effort through changes in sociosexuality and status-seeking behaviors.

Establishment and characterization of turtle liver organoids provides a potential model to decode their unique adaptations.

Painted turtles are remarkable for their freeze tolerance and supercooling ability along with their associated resilience to hypoxia/anoxia and oxidative stress, rendering them an ideal biomedical model for hypoxia-induced injuries (including strokes), tissue cooling during surgeries, and organ cryopreservation. Yet, such research is hindered by their seasonal reproduction and slow maturation. Here we developed and characterized adult stem cell-derived turtle liver organoids (3D self-assembled in vitro structures) from painted, snapping, and spiny softshell turtles spanning ~175My of evolution, with a subset cryopreserved.

Human leukocyte antigen class I antibody-activated endothelium promotes CD206+ M2 macrophage polarization and MMP9 secretion through TLR4 signaling and P-selectin in a model of antibody-mediated rejection and allograft vasculopathy.

HLA donor-specific antibodies (DSA) elicit alloimmune responses against the graft vasculature, leading to endothelial cell (EC) activation and monocyte infiltration during antibody-mediated rejection (AMR). AMR promotes chronic inflammation and remodeling, leading to thickening of the arterial intima termed transplant vasculopathy or cardiac allograft vasculopathy (CAV) in heart transplants. Intragraft-recipient macrophages serve as a diagnostic marker in AMR; however, their polarization and function remain unclear.

HLA-DPB1 genotype variants predict DP molecule cell surface expression and DP donor specific antibody binding capacity.

The contribution of alloresponses to mismatched HLA-DP in solid organ transplantation and hematopoietic stem cell transplantation (HCT) has been well documented. Exploring the regulatory mechanisms of DPB1 alleles has become an important question to be answered. In this study, our initial investigation focused on examining the correlation between the rs9277534G/A SNP and DPB1 mRNA expression.

Spatial multiomics of arterial regions from cardiac allograft vasculopathy rejected grafts reveal novel insights into the pathogenesis of chronic antibody-mediated rejection.

Cardiac allograft vasculopathy (CAV) causes late graft failure and mortality after heart transplantation. Donor-specific antibodies (DSAs) lead to chronic endothelial cell injury, inflammation, and arterial intimal thickening. In this study, GeoMx digital spatial profiling was used to analyze arterial areas of interest (AOIs) from CAV+DSA+ rejected cardiac allografts (N = 3; 22 AOIs total).

Evidence of the active participation of women in the intergroup conflict based on the use of aggression and cooperation.

Intergroup conflict has been a persistent aspect of human societies since the emergence of our species. Various researchers have proposed that competition between groups has acted as a key selective force throughout human evolutionary history. Such intergroup competition for limited resources exacerbated the expression of intergroup aggression and intragroup cooperation.

The Transplant Bellwether: Endothelial Cells in Antibody-Mediated Rejection.

Ab-mediated rejection of organ transplants remains a stubborn, frequent problem affecting patient quality of life, graft function, and grant survival, and for which few efficacious therapies currently exist. Although the field has gained considerable knowledge over the last two decades on how anti-HLA Abs cause acute tissue injury and promote inflammation, there has been a gap in linking these effects with the chronic inflammation, vascular remodeling, and persistent alloimmunity that leads to deterioration of graft function over the long term. This review will discuss new data emerging over the last 5 y that provide clues into how ongoing Ab-endothelial cell interactions may shape vascular fate and propagate alloimmunity in organ transplants.

The Significance of Major Histocompatibility Complex Class I Chain-related Molecule A in Solid Organ and Hematopoietic Stem Cell Transplantation: A Comprehensive Overview.

Improving long-term allograft survival and minimizing recipient morbidity is of key importance in all of transplantation. Improved matching of classical HLA molecules and avoiding HLA donor-specific antibody has been a major focus; however, emerging data suggest the relevance of nonclassical HLA molecules, major histocompatibility complex class I chain-related gene A (MICA) and B, in transplant outcomes. The purpose of this review is to discuss the structure, function, polymorphisms, and genetics of the MICA molecule and relates this to clinical outcomes in solid organ and hematopoietic stem cell transplantation.

JAKinibs prevent persistent, IFNγ-autonomous endothelial cell inflammation and immunogenicity.

The adhesion and subsequent activation of T cells is a critical step in local inflammatory responses, particularly of alloreactive leukocytes in rejection of transplanted donor tissue. Interferon (IFN)γ is an adaptive cytokine that promotes endothelial cell (EC) expression of pro-adhesive factors and costimulatory molecules. We recently reported that IFNγ-induced endothelial cell antigen-presenting capacity was protracted after cytokine withdrawal.

New insights into maladaptive vascular responses to donor specific HLA antibodies in organ transplantation.

Transplant vasculopathy (TV) causes thickening of donor blood vessels in transplanted organs, and is a significant cause of graft loss and mortality in allograft recipients. It is known that patients with repeated acute rejection and/or donor specific antibodies are predisposed to TV. Nevertheless, the exact molecular mechanisms by which alloimmune injury culminates in this disease have not been fully delineated.

Virtual and Reality: An Analysis of the UCLA Virtual Crossmatch Exchanges.

The "virtual" crossmatch (VXM) has become a critical tool to predict the compatibility between an organ donor and a potential recipient. Yet, nonstandardized laboratory practice can lead to variability in VXM interpretation. Therefore, UCLA's VXM Exchange survey was designed to understand factors that influence the variability of VXM prediction in the presence of HLA donor-specific antibody (DSA).

Transcriptomic thermal plasticity underlying gonadal development in a turtle with ZZ/ZW sex chromosomes despite canalized genotypic sex determination.

Understanding genome-wide responses to environmental conditions during embryogenesis is essential for discerning the evolution of developmental plasticity and canalization, two processes generating phenotypic variation targeted by natural selection. Here, we present the first comparative trajectory analysis of matched transcriptomic developmental time series from two reptiles incubated under identical conditions, a turtle with a ZZ/ZW system of genotypic sex determination (GSD), , and a turtle with temperature-dependent sex determination (TSD), . Results from our genome-wide, hypervariate gene expression analysis of sexed embryos across five developmental stages revealed that substantial transcriptional plasticity in the developing gonads can persist for >145 Myr, long after the canalization of sex determination via the evolution of sex chromosomes, while some gene-specific thermal sensitivity drifts or evolves anew.

Sensitization in transplantation: Assessment of Risk 2022 Working Group Meeting Report.

The Sensitization in Transplantation: Assessment of Risk workgroup is a collaborative effort of the American Society of Transplantation and the American Society of Histocompatibility and Immunogenetics that aims at providing recommendations for clinical testing, highlights gaps in current knowledge, and proposes areas for further research to enhance histocompatibility testing in support of solid organ transplantation. This report provides updates on topics discussed by the previous Sensitization in Transplantation: Assessment of Risk working groups and introduces 2 areas of exploration: non-human leukocyte antigen antibodies and utilization of human leukocyte antigen antibody testing measurement to evaluate the efficacy of antibody-removal therapies.

DNA damage and somatic mutations in mammalian cells after irradiation with a nail polish dryer.

Ultraviolet A light is commonly emitted by UV-nail polish dryers with recent reports suggesting that long-term use may increase the risk for developing skin cancer. However, no experimental evaluation has been conducted to reveal the effect of radiation emitted by UV-nail polish dryers on mammalian cells. Here, we show that irradiation by a UV-nail polish dryer causes high levels of reactive oxygen species, consistent with 8-oxo-7,8-dihydroguanine damage and mitochondrial dysfunction.

A Cautionary Tale of Sexing by Methylation: Hybrid Bisulfite-Conversion Sequencing of Immunoprecipitated Methylated DNA in Turtles with Temperature-Dependent Sex Determination Reveals Contrasting Patterns of Somatic and Gonadal Methylation, but No Unobtrusive Sex Diagnostic.

: The gonads of , a turtle with temperature-dependent sex determination (TSD), exhibit differential DNA methylation between males and females, but whether the same is true in somatic tissues remains unknown. Such differential DNA methylation in the soma would provide a non-lethal sex diagnostic for TSD turtle hatchings who lack visually detectable sexual dimorphism when young. Here, we tested multiple approaches to study DNA methylation in tail clips of hatchlings, to identify differentially methylated candidate regions/sites that could serve as molecular sex markers To detect global differential methylation in the tails we used methylation-sensitive ELISA, and to test for differential local methylation we developed a novel hybrid method by sequencing immunoprecipitated and bisulfite converted DNA (MeDIP-BS-seq) followed by PCR validation of candidate regions/sites after digestion with a methylation-sensitive restriction enzyme.