MicroRNA Sequencing of Long-Term Estrogen Deprived Breast Cancer Cells Reveals a Potential Role for miR-181a in Estrogen-Independent Growth

Breast cancer is a genetically complex disease that affects over 230,000 people in the U.S. every year. Estrogen signaling has been shown to play a large role in the development and progression of breast tumors that express the estrogen receptor (ER). Thus, aromatase inhibitors (AIs), which prevent the synthesis of estrogen, have been increasingly valuable for the management of ER+ breast cancer. A frequent obstacle, however, is acquired resistance to AIs, characterized by heightened growth factor signaling and estrogen-independent growth. Another aspect of acquired AI resistance that is now being examined is the role of microRNA (miRNA). miRNAs are 18-22 base pair RNA molecules whose primary role is to inhibit expression of mRNA targets by inhibition of translation or by degradation of the mRNA. Here, we have conducted next-generation sequencing of the miRNAs from three breast cancer cell lines – one ER+ line that is estrogen-dependent (MCF-7), and two ER+ long-term estrogen deprived (LTED) models of estrogen-independent growth (MCF-7:5C and MCF-7:2A). We found that in the LTED MCF-7:5C and MCF-7:2A cells there were 338 and 241 miRNAs differentially expressed, respectively, compared to the MCF-7 cells. We also saw unique miRNA clusters expressed in each LTED cell line – on chromosome 14q32 in the MCF-7:5C cells and on chromosome 13q31 in the MCF-7:2A cells. Our initial in vitro work focused on the functional significance of miR-181a (overexpressed in both LTED cells). This work has shown that miR-181a is regulated by estrogen/ER signaling, that loss of miR-181a in the LTED MCF-7:5C cells has a significant effect on proliferation, and that overexpression of miR-181a increases the ability of MCF-7 cells to grow in an estrogen-deprived environment. Since our LTED MCF-7:5C cells are more sensitive to DNA damage and overexpress miR-181a, which targets BRCA1, it was surprising that these cells were not more sensitive to the PARP inhibitor olaparib, which may be explained by high basal expression of BRCA1. Overall, it is clear that the miRNA profile of estrogen-dependent breast cancer cells is unique from the estrogen-independent LTED cells, and miR-181a may have a functional role in the estrogen-independent phenotype of our LTED MCF-7:5C cells

Principal as caregiver of all: responding to needs of others and self

When the school buildings closed in the spring, educators and families faced unknown challenges of supporting students remotely and continuing to provide the necessary resources for student learning and well-being. Principals responded with advocacy and compassion. This is one of a series of briefs that focused on a ‘critical incident’ surrounding school closure and offers pragmatic suggestions to educational leaders as they continue to grapple with the disruptions of the pandemic

Environmental Rights for the 21st Century: A Comprehensive Analysis of the Public Trust Doctrine and Rights of Nature Movement

This Article contrasts two theoretically distinct approaches to pursuing related objectives of environmental protection: the public trust doctrine and the rights of nature movement. It reviews the development of public trust and rights of nature principles in both domestic and international legal contexts, and explores points of theoretical commonality and contrast between the two, giving special attention to the opposing systems of environmental ethics from which the anthropocentric public trust and ecocentric rights of nature principles arise. The marked jurisdictional variation associated with both approaches suggests their evolving and inchoate nature as a guarantor of environmental rights. Moreover, both are especially oriented toward the protection of waterways, suggesting the limitations of conventional environmental law to provide adequate protection, and the resulting resort to alternative means. After reviewing the historical origins of the public trust doctrine in Roman and English common law, the article recounts its reception and development in U.S. law, leading to extraordinary jurisdictional diversity along the axes of the resources to which the trust applies, what values the trust protects, what mechanisms of law vindicate trust principles, and diverging legal theories in different states about the nature of the doctrine itself. It offers a snapshot of the diversity of the doctrine in sample states of California, Idaho, Pennsylvania, Michigan, Colorado, Hawaii, and Florida, and then reviews the state of public trust principles in nations beyond the United States. It then provides an overview of the rights of nature movement, both internationally and domestically. It provides the first scholarly survey of major rights of nature laws enacted throughout the world, and then reviews a series of local rights of nature bills introduced and enacted in American municipalities and Native American tribes, as well as judicial and legislative efforts to block them. It especially focuses on unfolding disputes in Florida, where multiple local governments are experimenting with rights of nature ordinances, and Orange County voters adopted a Bill of Rights charter amendment to protect the local river system from extraction in the same year that the state legislature statutorily preempted local rights of nature ordinances from effect. Finally, it compares and contrasts the two approaches, considering how these diverging anthropocentric and biocentric frames of reference provide different answers to basic questions of environmental management. It asks whether the doctrines can provide mutual support or are destined to undermine one another. It also considers the ways each model is used as a tool of political advocacy in legislative and administrative contexts beyond litigation. Both partner failures in litigation with more promising impacts in the political arena, where the motivating ideas can become a galvanizing force for policy change. Indeed, the enormous jurisdictional variation among both approaches—each a mosaic, rather than a monolith—signals the extent to which they are still evolving, and may long remain inchoate vessels of advocacy into which the champions of vulnerable environmental values pour both their frustrations and their hopes

Mechanical Strength and Hydration Level of Heteromeles arbutifola and Eriogonium Cinerium

The purpose of this study was to explore the hydration levels and mechanical strength of two species native to the same area: the dry Mediterranean region of the Santa Monica Mountains. The plants in this area must make adaptations to dry and arid climates, and We will compare how they stack up against each other in terms of drought resistance. Using Hollywood (heteromeles arbutifola) and Buckwheat (Eriogonium cinerium) we studied the different hydration levels and mechanical strengths and compared them. Both H. Arbutifola and the E. Cinerium are expected to mechanically stronger when hydrated.. We also expect the H. Arbutifola to be less affected by the lack of hydration than the E. Cinerium. Our methods for this experiment include taking samples of each plant, and hydrating half of each species and allowing the other to dry out for four hours. After this is done, we used the instron mechanical strength machine and the pressure chamber to collect data on the mechanical strength and hydration levels of the leaves. We then compared the data statistically and our results showed that the hydrated Buckwheat and dehydrated Buckwheat were not significantly different in their mechanical strength. And that dehydrated Hollywood and hydrated Hollywood do not have significant mechanical strength difference. Finally the hydrated Hollywood and dehydrated Buckwheat do not have significantly different water pressures

HEALTH INSURANCE PORTABILITY AND ACCOUNTABILITY ACT OF 1996: Health & Public Welfare

The Standards for Privacy of Individually Identifiable Health Information (“Privacy Rule”) establish a standard for the use and protection of individuals’ health information and apply to certain covered entities or their business associates. Covered entities may only disclose an individual’s protected health information in limited situations. Covered entities or individuals that fail to comply with the Privacy Rule standards may be subject to civil or criminal penalties

Maximizing Societal Contributions of Latino Adults by Investing in Latino Children's Health Care

Focuses on the lack of preventive care and health insurance coverage for Latino children, and how this affects their health and school performance and impacts their ability to contribute as adults to California's economy and society

School Counseling Supervision in Challenging Times: The CAFE Supervisor Model

Given the increased need for school counselors to proactively address the pervasive achievement, opportunity, and attainment gaps, school counselor preparation should move from traditional supervision models to one with an equitable K-12 student outcomes focus. The Change Agent for Equity (CAFE) model presented can help school counselors-in-training foster a change agent identity, aimed at helping all K-12 students succeed and reach their postsecondary dreams. The CAFE model and the supervisor’s identity and supervision practices within the model are described. Additionally, internship assignments and rubrics are outlined and supervisory recommendations and implications are discussed

GausSN: Bayesian Time-Delay Estimation for Strongly Lensed Supernovae

We present GausSN, a Bayesian semi-parametric Gaussian Process (GP) model for time-delay estimation with resolved systems of gravitationally lensed supernovae (glSNe). GausSN models the underlying light curve non-parametrically using a GP. Without assuming a template light curve for each SN type, GausSN fits for the time delays of all images using data in any number of wavelength filters simultaneously. We also introduce a novel time-varying magnification model to capture the effects of microlensing alongside time-delay estimation. In this analysis, we model the time-varying relative magnification as a sigmoid function, as well as a constant for comparison to existing time-delay estimation approaches. We demonstrate that GausSN provides robust time-delay estimates for simulations of glSNe from the Nancy Grace Roman Space Telescope and the Vera C. Rubin Observatory's Legacy Survey of Space and Time (Rubin-LSST). We find that up to 43.6% of time-delay estimates from Roman and 52.9% from Rubin-LSST have fractional errors of less than 5%. We then apply GausSN to SN Refsdal and find the time delay for the fifth image is consistent with the original analysis, regardless of microlensing treatment. Therefore, GausSN maintains the level of precision and accuracy achieved by existing time-delay extraction methods with fewer assumptions about the underlying shape of the light curve than template-based approaches, while incorporating microlensing into the statistical error budget rather than requiring post-processing to account for its systematic uncertainty. GausSN is scalable for time-delay cosmography analyses given current projections of glSNe discovery rates from Rubin-LSST and Roman.Comment: 18 pages, 12 figures, submitted to MNRA

Substantiating harm reduction and supporting tobacco regulatory science

A framework for the assessment of novel next-generation tobacco and nicotine products with the potential to reduce health risks compared with cigarettes should integrate scientific studies incorpor..

The Rise and Fall of the Latino Dentist Supply in California: Implications for Dental Education

The purpose of this study was to determine the number of Latino dentists in California, identify the schools and countries where they were educated, and compare Latino dentist demographics with that of the state’s new demographics. From the 2000 California Department of Consumer Affairs list of 25,273 dentists, we identified Latino U.S. dental graduates (USDGs) by “heavily Hispanic” surnames and Latino international dental graduates (IDGs) by country and school of graduation. From the 2000 U.S. census Public Use Microdata Sample (PUMS), we described Latino dentist characteristics such as Spanish language capacity and practice location. The number of Latino dentists acquiring licenses to practice in California has fallen dramatically, by nearly 80 percent, between 1983 and 2000. This decline is not merely an affirmative action issue; it results in an issue of access. Latino dentists are far more likely to speak Spanish and be located in a heavily Latino area than non-Latino dentists. Currently, although the supply of Latino dentists is dwindling, the Latino population is growing rapidly. In California and out-of-state schools, first-year matriculation of Latino USDG must increase. Further, non-Latino dentists should be prepared and given incentives to learn Spanish and locate practices in areas of need. The reintroduction of IDG Latino dentists needs to be seriously considered