Recommendations from transgender healthcare consumers in rural areas

Purpose: Scholars indicate that rates of mental and physical health issues (e.g., substance use, anxiety, depression) may be much higher among transgender individuals relative to the general population. This disparity may be even greater for transgender individuals in rural areas. Clinical researchers suggest using affirmative therapeutic approaches and interventions to address the health concerns of transgender individuals, specifically to connect individuals with the transgender community. However, little is known about the content of information that is shared in transgender communities in rural areas.Method: For this qualitative study, researchers asked transgender individuals in rural areas (n = 10) what recommendations they would offer to other transgender individuals in rural areas regarding healthcare access.Results: Results were organized into four domains: Access care, Quality control, Difficulties, and Mentorship. Within these domains, we identified 11 sub-domains: Get physical healthcare, Get mental healthcare, Provider search, Provider vetting, Treatment verification, It will be difficult, Know who you are, Believe in yourself, Move, Connect to community, and Other.Conclusions: We discuss implications of our findings for healthcare provision in rural areas, and we provide recommendations for future research.Peer reviewedCounseling and Counseling Psycholog

Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.

Actinins are strain-sensing actin cross-linkers that are ubiquitously expressed and harbor mutations in human diseases. We utilize CRISPR, pluripotent stem cells, and BioID to study actinin interactomes in human cardiomyocytes. We identify 324 actinin proximity partners, including those that are dependent on sarcomere assembly. We confirm 19 known interactors and identify a network of RNA-binding proteins, including those with RNA localization functions. In vivo and biochemical interaction studies support that IGF2BP2 localizes electron transport chain transcripts to actinin neighborhoods through interactions between its K homology (KH) domain and actinin\u27s rod domain. We combine alanine scanning mutagenesis and metabolic assays to disrupt and functionally interrogate actinin-IGF2BP2 interactions, which reveal an essential role in metabolic responses to pathological sarcomere activation using a hypertrophic cardiomyopathy model. This study expands our functional knowledge of actinin, uncovers sarcomere interaction partners, and reveals sarcomere crosstalk with IGF2BP2 for metabolic adaptation relevant to human disease

A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.

Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients

Capsule carbohydrate structure determines virulence in Acinetobacter baumannii

Acinetobacter baumannii is a highly antibiotic-resistant bacterial pathogen for which novel therapeutic approaches are needed. Unfortunately, the drivers of virulence in A. baumannii remain uncertain. By comparing genomes among a panel of A. baumannii strains we identified a specific gene variation in the capsule locus that correlated with altered virulence. While less virulent strains possessed the intact gene gtr6, a hypervirulent clinical isolate contained a spontaneous transposon insertion in the same gene, resulting in the loss of a branchpoint in capsular carbohydrate structure. By constructing isogenic gtr6 mutants, we confirmed that gtr6-disrupted strains were protected from phagocytosis in vitro and displayed higher bacterial burden and lethality in vivo. Gtr6+ strains were phagocytized more readily and caused lower bacterial burden and no clinical illness in vivo. We found that the CR3 receptor mediated phagocytosis of gtr6+, but not gtr6-, strains in a complement-dependent manner. Furthermore, hypovirulent gtr6+ strains demonstrated increased virulence in vivo when CR3 function was abrogated. In summary, loss-of-function in a single capsule assembly gene dramatically altered virulence by inhibiting complement deposition and recognition by phagocytes across multiple A. baumannii strains. Thus, capsular structure can determine virulence among A. baumannii strains by altering bacterial interactions with host complement-mediated opsonophagocytosis

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages

African linguistics on the prairie: Selected papers from the 45th Annual Conference on African Linguistics

African Linguistics on the Prairie features select revised peer-reviewed papers from the 45th Annual Conference on African Linguistics, held at the University of Kansas. The articles in this volume reflect the enormous diversity of African languages, as they focus on languages from all of the major African language phyla.  The articles here also reflect the many different research perspectives that frame the work of linguists in the Association for Contemporary African Linguistics. The diversity of views presented in this volume are thus indicative of the vitality of current African linguistics research. The work presented in this volume represents both descriptive and theoretical methodologies and covers fields ranging from phonetics, phonology, morphology, typology, syntax, and semantics to sociolinguistics, discourse analysis, language acquisition, computational linguistics and beyond.  This broad scope and the quality of the articles contained within holds out the promise of continued advancement in linguistic research on African languages