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Cancer cells utilize lipid droplets to survive chemotherapeutic stress
No full textOver 30,000 men in the United States die from metastatic prostate cancer each year. Metastatic cancer remains incurable as cancer cells become resistant to all known therapies. Despite decades of research, the source of therapeutic resistance is still largely unknown.
It is recognized that lipid reprogramming has a direct link to therapy desensitization and assists with cancer survival and success. Cancer associated alterations in lipid metabolism include increased lipid droplets (LDs) and enhanced lipid mobilization. Lipid droplets have canonically been known as storage reservoirs but have also recently come to light as an organelle that circumvents toxic stress. Higher levels of lipid droplets are associated with higher tumor aggressiveness and chemotherapy resistance in cancer. Prostate cancer cells have previously shown the ability to increase their levels of lipid droplets under stress. Lipid droplets are central anti-lipotoxic organelles that control cellular lipotoxicity by sequestering toxic or damaged lipids into inert triglycerides, cholesterol esters, and acyl ceramides. Sequestration of free fatty acids and damaged lipids into lipid droplets allows for lower lipotoxicity and lower lipid peroxidation in cells and higher chances of survival and future proliferation.
To determine the importance of lipid droplets in cancer we used database searches, metabolomic profiling, lipidomic profiling, live cell imaging, TEM, western blotting, flow cytometry, IHC, and qPCR. We discovered that PLIN1 (an exclusive lipid droplet surface protein), and DGAT1 (an enzyme that catalyzes the conversion of DAG and fatty acyl CoA to TAG which is the main component of lipid droplets) are higher in prostate cancer patients with lower disease-free survival and higher Gleason score. This clinical data indicates that more aggressive prostate cancer is most likely associated with higher levels of lipid droplets.
Our in vitro research demonstrates that cancer cells that survive chemotherapy have a significantly elevated level of lipid droplets in tandem with significantly elevated levels of oxidative stress. The elevation of lipid droplets in tandem with oxidative stress is indicative of lipid droplets sequestering damaged lipids from higher oxidative stress levels. We also established that lipid droplets form in cancer cells as soon as chemotherapy is applied suggesting a crucial method for avoiding lipotoxicity, lipid peroxidation, and cell death. To target lipid droplets in cancer we utilized pharmacological or genetic knockdown methods. Both methods were successful in significantly lowering lipid droplets in cancer cells. This inhibition allowed cancer cells to be sensitized to chemotherapy and resulted in lower viability of these cells.
Overall, our research proposes lipid droplets as important organelles that sequester toxic or damage lipids to promote survival. This work emphasizes the need for a dual treatment option of chemotherapy and lipid droplet inhibitors to advance the field towards more effective treatments for patients
Impact Evaluation of Flashlight360 in Mountain View Public Schools: Year 1
Get PDFThis study examined the effectiveness of Flashlight360 by conducting a retrospective, mixed-methods quasi-experimental (ED) in Grades 1-12 during the 2022-23 school year in a large western state school district. Outcome measure included comparing gains in speaking and writing achievement on the WIDA assessment administered to students in 37 schools implementing Flashlight360 to those of 45 similar schools that did not use the program. Results of the main impact analyses showed that Flashlight360 had a significant positive impact on WIDA ACCESS Overall scale scores, with treatment students outscoring matched comparison students by nearly 5 points. The effect size of this impact was 0.13 SDs, indicating a small-to-medium practical impact. Submission scores were significantly positively related to spring 2023 WIDA ACCESS Overall scores, with observed Pearson correlations ranging from .40 to .49 in magnitude
Impact Evaluation of Imagine MyPath in Moline-Coal Valley School District
Get PDFThe current study was a mixed-methods evaluation designed to provide efficacy evidence for Imagine Learning’s Imagine MyPath program, as well as data regarding program implementation and teacher perceptions. Achievement impacts were determined by comparing treatment students in kindergarten in the Moline-Coal Valley School District to comparison students identified by NWEA’s Similar Schools Report who did not use the program.
Results of the main impact analyses showed mixed patterns of results regarding the efficacy of Imagine MyPath. A significant positive impact of Imagine MyPath on student mathematics achievement gains was evidenced, with treatment students outgaining virtual comparison students by slightly more than 2 points on the NWEA MAP Growth Mathematics assessment. Perceptions of the Imagine MyPath program from Moline-Coal Valley School District teachers were generally positive. Overall, the majority of teachers agreed they would like to use the program again in the future and would recommend it to others. Teachers were highly positive regarding the organization of the program and its impact on student learning. Most teachers agreed that Imagine MyPath helped students improve their reading and mathematics skills and that the program addressed gaps in their knowledge about these subjects. They also largely agreed that the program placed students at the appropriate level initially, challenged them appropriately throughout the program, presented them with content appropriate to their skill level, motivated them to persist through difficult content, and met the needs of diverse learners.Weld Nort
Utilizing High School Environmental Science Capstone Projects to Support District-Level Sustainability Goals in Porterville Unified School District
Get PDFThe integration of environmental sustainability into high school curricula has become imperative, emphasizing the significance of concepts such as climate change, biodiversity, and natural resource management for informed global citizenship. In particular, capstone projects have emerged as vital components of high school environmental education, offering opportunities to advance sustainability in local communities and reduce greenhouse gas emissions. Porterville Unified School District (PUSD) has been partnering with the non-profit organization Climate Action Pathways for Schools (CAPS) to address environmental and sustainability issues, resulting in the formation of the PUSD Energy & Sustainability Program with overarching goals of reducing district greenhouse gas emissions by 80% by 2030 and achieving at least $500,000 in annual energy savings by 2030. CAPS has employed student interns to accomplish this task. The Environmental Science Academy (ESA), a cohorted program of study at Monache High School,within Porterville Unified School District, focuses on environmental education and activism, culminating in capstone projects where each student applies their knowledge to a real-world problem.
This paper will make recommendations in order to utilize ESA capstone projects to help Porterville Unified School District meet district-level sustainability goals. The hypothesis is that in order to meet PUSD’s district-level sustainability goals as outlined by CAPS, student involvement needs to expand beyond limited student internships and include student capstone projects. The results of CAPS interns’ work were considered as a baseline for expanding sustainability initiatives into capstone project curricula. This work was reflected in the data collected from electricity and natural gas bills which were used to analyze savings and emissions since the baseline year. Effective integration of capstone projects is based on interdisciplinary collaboration, community involvement, and real-world alignment with current sustainability challenges. A structured approach to project development and evaluation is essential, ensuring the seamless synchronization between theoretical academic concepts and applied environmental conservation efforts.
High school capstone projects have the potential to empower students, foster community engagement, and contribute to school districts' sustainability goals. These projects provide hands-on experiences, promote collaboration, and develop essential skills, preparing students for future career opportunities in sustainability-related fields. By actively engaging in research, data collection, and analysis, students gain a practical understanding of concepts such as energy conservation, waste reduction, and biodiversity preservation
ENERGY TRANSITION IN DEVELOPING COUNTRIES: A CASE STUDY OF CHINA AND A COMPARATIVE ANALYSIS WITH INDIA
Get PDFAs developing nations like China and India surge onto the global stage, their rapid expansion comes at a cost: a growing dependence on fossil fuels that fuels the looming greenhouse gas crisis. These two rising powers face the monumental challenge of energy transition, disentangling their economies from the carbon legacy of the past. Despite that China and India both put in enormous efforts in energy transition, they have different approaches.
This paper focuses on the comparison of China and India in energy transition through analyses of data and policy frameworks. This paper also dissects the interplay of three key elements, which are regulatory structures shaping policy, technological advancements defining energy options, and financial mechanisms driving investments. This research discusses how the three elements interact and influence India and China in their path towards a cleaner and greener future by examining both quantitative data and qualitative factors.
China benefited a lot from its centralized government because it can implement any infrastructure that can facilitate renewable energy deployment and advancement efficiently in a top-down manner. India, on the other hand, does not have the benefits of being a centralized nation. It still has fragmented regulatory frameworks that encourage innovation and entrepreneurial vigor in renewable technologies. Understanding China and India's unique energy transition journeys is crucial for policymakers, technology developers, and social activists to examining China and India’s successes and challenges to seek to break free from fossil fuel dependence. This thesis intends to provide actionable insights in policy design, technology deployment, and social mobilization, offering practical tools to build a sustainable future for all
INSURING CHANGE: EXPLORING THE ROLE OF INSURANCE IN DRIVING CLIMATE POSITIVE BEHAVIORS
Get PDFClimate change presents a complex nexus of challenges spanning environmental, social, and economic spheres, compelling global attention and action. Despite mounting commitments and awareness, a gap exists between current actions and there is a call for accelerated regulatory interventions to align with sustainable pathways. A crucial element in developing mitigation strategies involves understanding emissions contributions, facilitated by standards like the GHG Protocol. Increased corporate transparency on greenhouse gas (GHG) emissions intensifies pressures for emissions reduction across sectors, enabling targeted focus on high-emission areas for accelerated decarbonization efforts.
Recognizing the potential of insurance as a tool for influencing climate-positive behaviors, stakeholders are exploring avenues to leverage property and casualty insurance. While insurance traditionally served as a risk management tool, its role in addressing climate change impacts, through mitigation and adaptation, is gaining prominence. Insurance companies' ability to influence customer behaviors through products and pricing, though not traditionally aligned with climate change mitigation, presents a new opportunity.
This paper seeks to explore insurance's role in steering climate-positive behaviors. It delves into the feasibility and impact of insurance as a behavior-influencing tool in climate change mitigation and adaptation. Examining whether insurance can effectively influence behavior will shed light on its potential role in climate change action, shaping future engagements between the insurance industry and climate change. The investigation encompasses regulatory aspects, existing insurance products, their influence on behavior, and their potential implications for climate change mitigation efforts, particularly focusing on shifts towards sustainable practices, like the transition to electric or hybrid vehicles
HEAT RESILIENCY IN LOW-INCOME COMMUNITIES: A NEEDS ASSESSMENT OF SPACE CONDITIONING POLICIES AND PROGRAMS IN SOUTHERN CALIFORNIA
Get PDFHeat kills more people per year than the combined total of floods, storms, and lightning. California is expected to face increasingly warmer temperatures, as well as more frequent and longer heat waves that can endanger the health of the public, and in some cases, cause death. Low-income and disadvantaged communities are likely to suffer a disproportionate amount of those deaths during extreme heat events because this vulnerable population is challenged with adapting to extreme heat. One of the most readily available heat adaptation technologies is air conditioning (A/C). However, this technology that is so ubiquitous to most people, especially those with more affluence, is not readily available to some low-income populations in Southern California primarily due to its high purchase and installation costs. Using several public information sources, this Needs Assessment identified 231 vulnerable census tracts making up 290,489 households, in a four-county Southern California region for which a percentage likely doesn’t have A/C. Further, available federal, state, and local programs that offer A/C to income-qualified households were inventoried to determine if there was enough funding and enabling policies to directly install A/C in the targeted households. The Needs Assessment concludes that there is a funding gap of 2.2 billion in current programs that could address this need and ensure the identified vulnerable population has the adaptive capacity for extreme heat
MID-CANOPY HEIGHT AND LEAF THICKNESS ARE CORRELATED TO CATERPILLAR (LEPIDOPTERA) HABITAT CHOICE IN AN EASTERN USA, TEMPERATE, OAK-HICKORY FOREST
Get PDFMechanical and chemical plant structures are important factors in determining herbivorous insect assemblages. During the summer of 2017, 2015 caterpillars (Lepidoptera), classified as either shelter builders or exposed feeders, were collected by hand from 40 felled trees in an oak-hickory temperate forest located in Toms Brook (Shenandoah County, Virginia, eastern USA). Preserved caterpillars were identified by morphological and molecular characteristics. I explored whether there are statistical relationships between caterpillar abundance and plant mechanical traits, such as leaf thickness, leaf toughness, and relative tree height. As a group, caterpillars were concentrated in the relative middle height of each trees’ canopy. Leaf thickness - but not leaf toughness - was correlated to overall caterpillar abundance. Specifically, shelter builders were more abundant on thicker leaves, and, in contrast, exposed feeding caterpillars were more abundant on thinner leaves. Whether caterpillars are shelter builders or exposed feeders, it appears that their presence within a tree varies substantially, and that this variation is related, in part, to relative canopy location and to leaf thickness. Also, these results support the hypothesis that leaves in the relative upper canopy, as defined by a relative tree height formula, experience reduced herbivory possibly due to abiotic factors, such as decreased water availability and increased exposure to UV radiation both of which reduce their nutritional content and palatability
Oral History of Rose Buttress
No full textThis oral history about transgender experience in Baltimore was recorded as part of Vintage T, a public humanities project led by Monica Stevens, Jamie Grace Alexander, and Rahne Alexander and sponsored by Sistas of the “T” and the Winston Tabb Special Collections Research Center. Vintage T was launched in 2023 to document and archive the perspectives, strategies, and personal histories of trans individuals in Baltimore, thereby preserving valuable traditions within trans communities
Neurotoxicity due to Environmental complex Metal Mixtures EXposure (NEMMEX)
Get PDFThis project explores the neurodevelopmental toxicity effect of individual metals lead (Pb), arsenic (As), cadmium (Cd), and chromium (Cr), and their metal mixture (abbreviated as PACC), which are highly ranked on the ASTDR’s priority list. Despite many studies linking heavy metals to neurotoxicity, there are substantial gaps in understanding of the precise molecular mechanisms and the pathways leading to these harmful outcomes. This study is to address the fundamental knowledge gaps concerning the underlying molecular mechanisms, adverse outcome pathways (AOPs), and the intricate connections between sex, delayed effects, and exposure to the PACC mixture. Behavioral assessments using EPM and NOR tests showed heightened anxiety and reduced cognition in mixed metals-exposed mice. Gene expression analysis revealed gender-dependent downregulation of the Gsta2 gene in female mice exposed to Cd, highlighting sex-specific responses in metal-induced gene regulation. The observed lower GSH/GSSG ratio indicated an altered redox balance, suggesting increased oxidative stress. This study provides an insight into gender specific metal neurotoxicity, behavioral outcomes, and molecular responses to metal mixtures emphasizing the need for research into the metal toxicity effect on neurodevelopment