RESUMEN
N-alpha-terminal acetylation is a modification process that occurs cotranslationally on most eukaryotic proteins. The major enzyme responsible for this process, N-alpha-terminal acetyltransferase, is composed of the catalytic subunit ARD1A and the auxiliary subunit NAT1. We cloned, characterized, and studied the expression pattern of Ard1b (also known as Ard2), a novel homolog of the mouse Ard1a. Comparison of the genomic structures suggests that the autosomal Ard1b is a retroposed copy of the X-linked Ard1a. Expression analyses demonstrated a testis predominance of Ard1b. A reciprocal expression pattern between Ard1a and Ard1b is also observed during spermatogenesis, suggesting that Ard1b is expressed to compensate for the loss of Ard1a starting from meiosis. Both ARD1A and ARD1B can interact with NAT1 to constitute a functional N-alpha-terminal acetyltransferase in vitro. The expression of ARD1B protein can be detected in mouse testes but is delayed until the first appearance of round spermatids. In a cell culture model, the inclusion of the long 3' untranslated region of Ard1b leads to reduction of luciferase reporter activity, which implicates its role in translational repression of Ard1b during spermatogenesis. Our results suggest that ARD1B may have an important role in the later course of the spermatogenic process.
Asunto(s)
Acetiltransferasas/genética , Arilamina N-Acetiltransferasa/metabolismo , Isoenzimas/metabolismo , Espermatogénesis/genética , Testículo/citología , Regiones no Traducidas 3' , Acetiltransferasas/química , Acetiltransferasas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Animales , Arilamina N-Acetiltransferasa/genética , Secuencia de Bases , Células CHO , Línea Celular , Clonación Molecular , Cricetinae , Cricetulus , Perfilación de la Expresión Génica , Regulación del Desarrollo de la Expresión Génica , Genes Reporteros , Inmunoprecipitación , Isoenzimas/química , Isoenzimas/genética , Masculino , Meiosis , Ratones , Datos de Secuencia Molecular , Acetiltransferasa A N-Terminal , Acetiltransferasa E N-Terminal , Especificidad de Órganos , Péptidos/inmunología , Unión Proteica , Proteínas Recombinantes de Fusión/metabolismo , Retroelementos , Alineación de Secuencia , Espermatozoides/crecimiento & desarrollo , Espermatozoides/metabolismo , Testículo/crecimiento & desarrollo , Testículo/metabolismoRESUMEN
OBJECTIVE: To create an index that would serve as a simple tool to measure the quality of hospital care by race and ethnicity. STUDY DESIGN: Following extensive review of existing disparities indices, we created a disparities quality index (DQI) designed to easily measure differences in the quality of care hospitals deliver to different populations. The DQI uses performance data already collected by virtually all hospitals. It highlights areas where there are large numbers of patients in a specific population receiving potentially lower-quality care. SETTING: Data were collected from 2 acute care hospitals that participated in a multihospital collaborative. DATA COLLECTION/EXTRACTION METHODS: We applied the DQI to 2 hospitals' quality data, specifically to their performance on the Hospital Quality Alliance measure for patients with heart failure who were receiving angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. RESULTS: The DQI was simple to apply and was able to measure differences in the care of different ethnic groups. It also detected changes in disparities over time. CONCLUSIONS: The DQI can help hospitals and other providers focus on the domain of equity in their quality-improvement efforts. Further testing is required to determine its applicability for community-wide equity projects.
Asunto(s)
Indización y Redacción de Resúmenes , Disparidades en Atención de Salud , Calidad de la Atención de Salud/normas , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Etnicidad , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Grupos Minoritarios , Receptores de Angiotensina/uso terapéutico , Estadística como Asunto , Estados Unidos , Disfunción Ventricular Izquierda/tratamiento farmacológicoRESUMEN
A novel heterozygous mutation A340T leading to the substitution of Phe for the conserved amino acid Ile114 was identified by nucleotide sequencing of the human LH/chorionic gonadotropin receptor (hLHR) of a patient with Leydig cell hypoplasia. This mutation is located in the third leucine-rich repeat in the ectodomain of the hLHR. In vitro expression studies demonstrated that this mutation results in reduced ligand binding and signal transduction of the receptor. Studies of hLHR constructs in which various amino acids were substituted for the conserved Ile114 showed that receptor activity is sensitive to changes in size, shape, and charge of the side chain. A homology model of the wild-type hLHR ectodomain was made, illustrating the packing of conserved hydrophobic side chains in the protein core. Substitution of Ile114 by Phe might disrupt intermolecular contacts between hormone and receptor. This mutation might also affect an LHR-dimer interaction. Thus, the I114F mutation reduces ligand binding and signal transduction by the hLHR, and it is partially responsible for Leydig cell hypoplasia in the patient.
Asunto(s)
Tumor de Células de Leydig/genética , Modelos Moleculares , Mutación Missense/genética , Proteínas/genética , Receptores de HL/genética , Secuencia de Bases , Línea Celular , AMP Cíclico/metabolismo , Citometría de Flujo , Humanos , Proteínas Repetidas Ricas en Leucina , Masculino , Microscopía Fluorescente , Datos de Secuencia Molecular , Análisis de Secuencia de ADNRESUMEN
A pre-posttest, randomized pilot study evaluated the effect of two selective prevention interventions on knowledge, attitudes, intentions, and behaviors to prevent and/or reduce substance use and risky sexual behaviors among 50 predominantly Mexican-American, low-income young women. Women were randomly assigned to either a risk and resilience workshop or a health information correspondence course. Comparison tests using t tests and chi-square analyses were conducted to determine the baseline equivalence and pre- and posttest effects of the interventions. Both interventions had consistently similar effects. Neither significantly decreased use of alcohol or cigarettes. Both interventions significantly improved attitude, sexual self-efficacy, and resilience scores. Contraceptive use increased among women in partnered relationships, and both condom use and contraceptive use increased among sexually active, single young women. Both interventions also had significant positive effects on reported ability to discuss precautions to prevent human immunodeficiency virus/acquired immunodeficiency syndrome with sexual partners. Study limitations and implications for clinical practice and future research are provided.