Unraveling genetic regulatory networks of mammalian retroelements

Advances in the science of toxicogenomics have opened the door to major advances in our understanding of the molecular basis of environmental pathogenesis and the role of environmental factors in human disease. This report summarizes major findings in the laboratory defining the molecular basis of L1 retroelement activation in mammalian cells and the architecture of gene regulatory networks involved in phenotypic control

Pharmacogenomics insights into precision pediatric oncology

PURPOSE OF REVIEW: Pharmacogenomic insights provide an opportunity to optimize medication dosing regimens and patient outcomes. However, the potential for interindividual genomic variability to guide medication dosing and toxicity monitoring is not yet standard of care. In this review, we present advances for the thiopurines, anthracyclines and vincristine and provide perspectives on the actionability of pharmacogenomic guidance in the future. RECENT FINDINGS: The current guideline on thiopurines recommends that those with normal predicted thiopurine methyltransferase and NUDT15 expression receive standard-of-care dosing, while \u27poor metabolizer\u27 haplotypes receive a decreased 6-mercaptopurine starting dose to avoid bone marrow toxicity. Emerging evidence established significant polygenic contributions that predispose to anthracycline-induced cardiotoxicity and suggest this knowledge be used to identify those at higher risk of complications. In the case of vincristine, children who express CYP3A5 have a significantly reduced risk of peripheral neuropathy compared with those expressing an inactive form or the CYP3A4 isoform. SUMMARY: The need for adequately powered pediatric clinical trials, coupled with the study of epigenetic mechanisms and their influence on phenotypic variation and the integration of precision survivorship into precision approaches are featured as important areas for focused investments in the future

The development of abdominal aortic aneurysms in mice is enhanced by benzo(a)pyrene

Cigarette smoking has been strongly associated with abdominal aortic aneurysm (AAA), but the components of tobacco smoke involved in AAA have not been identified. Benzo(a)pyrene (BaP) is an important constituent in cigarette smoke capable of induction of alterations strikingly similar to the pathological changes seen during AAA development. We therefore hypothesized that BaP exposure contributes to the development of AAA. In this study, C57/B6J mice were treated with vehicle, angiotensin II (AngII) (0.72 mg/kg/day), BaP (10 mg/kg/week), or the combination of AngII and BaP, for 5 weeks, and then examined for incidence of AAA and pathological changes of the aortic wall. Results showed that incidence of AAA formation in C57/B6J mice treated with BaP and AngII was significantly higher than that in AngII-treated mice (7 of 12 compared to 2 of 12). Further, five mice in the group treated with AngII/BaP and one in the group treated with AngII exhibited AAA rupture and hematoma. BaP caused macrophage infiltration, disarray of elastic lamella, and loss of vascular smooth muscle cells (VSMCs). We conclude that BaP aggravates AAA formation and rupture in C57/B6J mice by promoting macrophage infiltration, degeneration of elastic lamella, and loss of VSMCs in the aortic wall

Hunger for Culture

The 2016 world premiere of Larissa FastHorse’s play Urban Rez, which Cornerstone Theater Company produced, presented a community-based theater experience in Los Angeles County (Tongva and Tataviam homelands). In this essay, our three co-authors utilize the concept of being a guest on Tongva land as a methodology to demonstrate Two-Spirit, Queer, and Trans representation within Indigenous theater. Through the work of the playwright, cast, and crew, the Urban Rez narrative asserted self-representation in opposition to settler imaginaries through community-based participatory storytelling. Urban Rez represented a pivot in the current American Theater landscape and a continuation of Indigenous theater legacies. Our essay offers a cross-collaboration between three performers from Urban Rez that represent a wide breadth of academic experiences, performance backgrounds, and community organizing to discuss queer, Two-Spirt, and trans experiences. The co-authors discuss the legacy of counter-narratives in Native theater, demonstrate sovereignty in the play, and utilize queer theory to understand an Indigenous queer experience on stage better. We provide a reflexive co-authorship to assert relationality in the face of heteropatriarchy and contend with our hunger for culture. The co-authors recognize the Urban Rez experience as one of the first major Indigenous theater productions in Los Angeles that included queer, Two-Spirit, and transgender characters that rejected justifying representation from a deficit narrative

Nivel de Cumplimiento del Protocolo de la Amenaza de Parto Pre-término en pacientes embarazadas con edad gestacional mayor de 22 semanas y menor de 37 semanas de gestaciones ingresadas en el servicio de Alto Riesgo Obstétrico en el Hospital Bertha Calderón Roque en el primer semestre del año 2016

Objetivo: Evaluar el cumplimiento de la aplicación del protocolo de la amenaza de parto pretérmino en las pacientes atendidas en la sala del alto riesgo obstétrico del Hospital Bertha Calderón en el primer semestre del año 2016 Material y método: Estudio descriptivo de corte transversal. Se estudiaron 60 pacientes con embarazos mayores de 22 semanas menores de 37 semanas que fueron ingresadas al área de alto riesgo obstétrico del Hospital Bertha Calderón Roque en el primer semestre del año 2016, con diagnóstico de amenaza de parto pretérmino. Se utilizó la lista de chequeo de la normativa 044. Resultados: Las mujeres en estudio, 24 de ellas eran menores de 19 años (48%). 35 mujeres no poseían antecedentes patológicos personales (70%). 26 mujeres que se había realizado más de 4 controles (52%). Con el estado del cuello uterino (borramiento menor del 50% con una dilatación menor de 3 cm y comprobando la integridad de las membranas) se constató en 36 de los expedientes (72%). relación a la indicación del uso de corticoides, 38 de los expedientes (76%) cumple con la aplicación. Conclusiones: La amenaza de parto pretérmino sobresale en la población en edades menores de 19 años. Los criterios clínicos diagnósticos cumplidos fueron la edad gestacionales y la evaluación del bienestar fetal. No se cumplieron en un 100% los criterios en la implementación del tratamiento no farmacológico. No se cumplieron en un 100% los criterios en la implementación del tratamiento farmacológico. Recomendaciones: A los directores de hospital, junto a los jefes de servicio que se ponga en práctica el mandato de la revisión de expedientes clínicos de mujeres con diagnóstico de amenaza de parto pretérmino, para identificar los puntos álgidos en los que no se está cumpliendo el protocolo de la amenaza de parto prematuro para hacerlos llegar al equipo médico y así poder mejorar la calidad de atención

Broad-host range expression vectors containing manipulated meta-cleavage pathway regulatory elements of the TOL plasmid

AbstractThe construction of pERD20 and pERD21, two broad-host range expression vectors, is described. The vectors contain the Pm promoter of the meta-cleavage pathway operon of the TOL plasmid pWWO; this promoter is present within a polylinker which provides a number of downstream cloning sites close to the transcription initiation site. Transcription from the Pm promoter in these vectors is controlled not by the natural positive regulator of Pm, the Xy1S protein, but by an Xy1S mutant analogue, Xy1S2tr6, which ??hibits an altered effector specificity and can mediate a 3–8-fold higher level of transcription than can Xy1S in a wide range of temperatures. Controlled expression of cloned genes can be achieved in a broad spectrum of Gram negative bacteria grown at a wide range of temperatures