Biomedical subjects

Elizabeth G Hill

Publications and source records attributed to Elizabeth G Hill.

7 recordsLinked to original sources

PubMed2026

Lysyl oxidase inhibition disrupts mitochondrial homeostasis to create vulnerability to ferroptosis in TNBC.

High metabolic heterogeneity and plasticity of triple-negative breast cancer (TNBC) contribute to therapy resistance, necessitating identification of therapeutic vulnerabilities. Here, we identify non-canonical functions of the extracellular matrix (ECM) remodeler, lysyl oxidase (LOX), in regulating glucose metabolism and mitochondrial homeostasis and show that inhibiting LOX generates targetable vulnerability to ferroptosis. Mechanistically, LOX interacts with PARKIN and its upstream kinase PINK1, which we identified as a substrate of LOX. LOX-mediated PINK1 oxidation suppresses PARKIN phosphorylation, stabilizing hypoxia-inducible factor 1-alpha (HIF-1α) and increasing glycolysis. Concomitantly, LOX inhibits PARKIN-mediated mitophagy and maintains mitochondria-ER contacts through VDAC1 stabilization, while the LOX-HSP90 complex promotes mitochondrial Ca2+ transport and ATP production. Inhibiting LOX suppresses glycolysis, disrupts mitochondrial dynamics, reduces OXPHOS and GPX4/FSP1, and induces compensatory DHODH activity. Our "one-two punch" approach combining LOX inhibition with clinical DHODH inhibitor suppresses tumor growth in vivo in chemo-free setting. Notably, LOX protein correlates with HIF-1α/GLUT1/GPX4 in TNBC patient tumors, supporting its clinical relevance.

Ferroptosis↗

PubMed2006

PrepMS: TOF MS data graphical preprocessing tool.

UNLABELLED: We introduce a simple-to-use graphical tool that enables researchers to easily prepare time-of-flight mass spectrometry data for analysis. For ease of use, the graphical executable provides default parameter settings, experimentally determined to work well in most situations. These values, if desired, can be changed by the user. PrepMS is a stand-alone application made freely available (open source), and is under the General Public License (GPL). Its graphical user interface, default parameter settings, and display plots allow PrepMS to be used effectively for data preprocessing, peak detection and visual data quality assessment. AVAILABILITY: Stand-alone executable files and Matlab toolbox are available for download at: http://sourceforge.net/projects/prepms

Algorithms↗

PubMed2006

The geography of power: statistical performance of tests of clusters and clustering in heterogeneous populations.

Heterogeneous population densities complicate comparisons of statistical power between hypothesis tests evaluating spatial clusters or clustering of disease. Specifically, the location of a cluster within a heterogeneously distributed population at risk impacts power properties, complicating comparisons of tests, and allowing one to map spatial variations in statistical power for different tests. Such maps provide insight into the overall power of a particular test, and also indicate areas within the study area where tests are more or less likely to detect the same local increase in relative risk. While such maps are largely driven by local sample size, we also find differences due to features of the statistics themselves. We illustrate these concepts using two tests: Tango's index of clustering and the spatial scan statistic. Furthermore, assessments of the accuracy of the 'most likely cluster' involve not only statistical power, but also spatial accuracy in identifying the location of a true underlying cluster. We illustrate these concepts via induction of artificial clusters within the observed incidence of severe cardiac birth defects in Santa Clara County, CA in 1981.

California↗

PubMed2006

Chick embryos exposed to trichloroethylene in an ex ovo culture model show selective defects in early endocardial cushion tissue formation.

BACKGROUND: Formation of the primitive heart is a critical step for establishing a competent circulatory system necessary for continued morphogenesis, and as such has significant potential as a target for environmental insult. The goal of this study was to identify the initial cellular events that precede more superficially observable abnormalities resulting from exposing early chick embryos to trichloroethylene (TCE). METHODS: A whole embryo culture method was used to assess the susceptibility of endocardial epithelial-mesenchymal transformation in the early chick heart to TCE. This method has the benefits of maintaining the anatomical relationships of developing tissues and organs, instantaneously exposing precisely staged embryos to quantifiable levels of TCE in a protein-free medium, and the ability to directly monitor developmental morphology. RESULTS: A minority of embryos (Hamburger and Hamilton [HH] stage 13-14) exposed to TCE (10-80 ppm) were not viable after 24 hr in culture and exhibited a variety of gross malformations in a dose-dependent fashion. However, the majority of treated embryos remained viable and developed into HH stage 17 embryos that were superficially indistinguishable from vehicle-treated controls. Further analysis of the hearts of these superficially normal embryos by whole-mount confocal microscopy revealed selective reduction in the number of atrioventricular canal mesenchymal cells. Additionally, those mesenchymal cells that did develop migrated abnormally as long thin cords of adherent cells. CONCLUSIONS: The regional selectivity of these effects in the chick heart suggests a critical window of susceptibility to TCE in the epithelial-mesenchymal transformation of atrioventricular canal endocardium.

Animals↗

PubMed2006

Study design for calibration of clinical examiners measuring periodontal parameters.

BACKGROUND: We present an approach to examiner calibration study design where the number of calibration subjects is based on a specified margin of error (half-width of the 95% confidence interval [CI]) of the percentage of agreement (exact and within 1 mm) for both intra- and interexaminer reliability assessments. METHODS: An experienced standard examiner (S) trained three dental hygienists (A, B, and C) in correct procedures for obtaining a variety of periodontal measures. Duplicate measurements of probing depth (PD [mm]) and the free gingival margin to the cemento-enamel junction (CEJ-GM [mm]) were obtained in a pilot study to design a formal examiner calibration study, where sample sizes were adjusted for the effects of within-subject clustering of binary indices of agreement. RESULTS: Within-subject clustering of agreement indices resulted in an approximate four-fold increase in the variance of the estimates of percentage of agreement with the standard. PD and CEJ-GM percentage of exact agreement measurements (95% CI) for each examiner-standard pair, respectively, were as follows: AS=55% (48%, 61%) and 70% (62%, 78%); BS=52% (45%, 59%) and 73% (63%, 82%); and CS=55% (50%, 61%) and 72% (65%, 79%). The corresponding 95% CIs unadjusted for the effects of clustering underestimated the margin of error associated with the estimates of exact agreement by as much as 57% for PD and 68% for CEJ-GM. CONCLUSION: Failure to account for dependence among site-level agreement indices results in a false sense of precision in the resulting reliability estimates and can lead to faulty inference.

Adolescent↗

PubMed2005

Violence and PTSD in Mexico: gender and regional differences.

OBJECTIVE: We examined the lifetime prevalence of violence in Mexico and how different characteristics of the violent event effect the probability of meeting criteria for lifetime post-traumatic stress disorder (PTSD). METHOD: We interviewed a probability sample of 2,509 adults from 4 cities in Mexico (Oaxaca, Guadalajara, Hermosillo, Mérida) using the Composite International Diagnostic Interview (CIDI). RESULTS: Lifetime prevalence of violence was 34%. Men reported more single-experience, recurrent, physical, adolescent, adulthood, and stranger violence; women more sexual, childhood, family, and intimate partner violence. Prevalence was generally higher in Guadalajara, though the impact was greater in Oaxaca compared to other cities. Of those exposed, 11.5% met DSM-IV criteria for PTSD. Probabilities were highest after sexual and intimate partner violence, higher for women than men, and higher in Oaxaca than other cities. CONCLUSIONS: It is important to consider the characteristics and the context of violence in order to develop effective prevention and intervention programs to reduce the exposure to and impact of violence.

Adolescent↗

PubMed2005

Maternal-fetal medicine specialist density is inversely associated with maternal mortality ratios.

OBJECTIVE: Our study's objective was to determine the relationship between state-specific maternal mortality ratios and the density of maternal-fetal medicine specialists. STUDY DESIGN: State maternal mortality ratios from 1994 to 2001 were calculated from the Centers for Disease Control and Prevention WONDER database. Practitioner distribution data were obtained from professional associations. Demographic information regarding states was gathered from the 2000 US census data. Bivariable and multivariable analyses were conducted with the use of Spearman correlations and Poisson regression, respectively. RESULTS: The median state maternal-mortality ratio was 7.5/100,000 live births. Our study showed that an increase of 5 maternal-fetal specialists per 10,000 live births results in a 27% reduction in the risk of maternal death (relative risk [RR] = 0.73, 95% CI = 0.58-0.93, P = 0.012). This risk reduction was based on a multivariable Poisson regression model that included the following variables and their significant interactions: state-specific percentages of mothers in poverty, mothers without a high school diploma, minority mothers, and teenage mothers. CONCLUSION: The density of maternal-fetal medicine specialists is significantly and inversely associated with maternal mortality ratios, even after controlling for state-level measures of maternal poverty, education, race, age, and their significant interactions.

Adult↗