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Surface Keratin 1, A Tumor-Selective Peptide Target in Human Triple-Negative Breast Cancer
Get PDFTargeting drugs to cancer cells via overexpressed cell-surface receptors has emerged as an effective therapeutic strategy for several cancers. However, identifying cell-surface receptors that allow selective uptake of targeting ligands by cancer cells—while sparing normal cells—remains a challenge, especially for triple-negative breast cancer (TNBC), which lacks a well-defined receptor for targeted delivery. In this study, immunohistochemical (IHC) analysis revealed that human TNBC patient tissues have significantly higher levels of keratin 1 (K1) compared to normal breast tissues. Among TNBC tissues, grade 3 tumors showed significantly higher (threefold) K1 expression compared to grade 2 tumors. We analyzed human TNBC and normal mammary epithelial cells to detect K1 from cell lysates using three methods: mass spectrometry, peptide mass fingerprinting, and Western blot. TNBC cell lysates confirmed the presence and high expression levels of 67 kDa K1. Importantly, intact cells showed that K1 is uniformly present on the surface of TNBC cells, while no or minimal cell-surface K1 was found in normal mammary epithelial cells using immunofluorescence confocal microscopy. Further, we show that cell-surface K1 was utilized by TNBC-selective peptide 18–4 for its uptake via cell-surface receptor (K1)-mediated endocytosis in TNBC cells, and the presence of peptide 18–4 did not affect the assembly of endogenous cytoplasmic K1. Taken together, our results demonstrate that K1 is overexpressed in human TNBC, and cell-surface K1 represents a promising new target for directed delivery in TNBC using targeting ligands such as peptide 18–4
Production of Dissolved Organic Matter from Lily Pads (Nymphaea odorata) in a Mesotrophic Freshwater Lake
No full textMacrophytes are potentially an important dissolved organic matter (DOM) source in lakes. To assess the effect of lily pads (Nymphaea odorata) on DOM, optical properties and dissolved organic carbon concentrations (DOC) were measured over a year in Lake Louise, Pacific Northwest, USA. Lily pads were widespread around the shoreline during summer, dying back in the fall. Some optical indices (slope ratio, index of recent autochthonous contribution, fluorescence index) indicated the lake was dominated by DOM from terrestrial sources for most of the year. Indicators of autochthonous production in a few winter samples were attributed to phytoplankton. DOC concentrations and precipitation were not correlated, but DOC was positively correlated with absorption coefficient at 350 nm (α350). DOC and α350 were highest in summer and decreased in the winter wet season, which would be consistent with an in situ lake source being diluted by rainfall as a possible explanation for this. Excitation-emission matrix fluorescence spectra of lake waters and lily pad leachates indicated humic and protein material components. The plant leachates had slope ratio, fluorescence index, and index of recent autochthonous contribution values consistent with terrestrially derived DOM and lake waters. Higher DOC and α350 in the summer were associated with some lower optical indices (specific ultra-violet absorbance, spectral slope, humification index, fluorescence/absorbance ratio ratios), consistent with material derived from lily pads. Estimates indicated lily pads contributed as much to the lake DOM pool in the summer dry season as watershed terrestrial inputs in the winter wet season, suggesting that DOM production by lily pads may account for a significant portion of the carbon pool in smaller lakes
Moral Judgment Toward Individuals in Consensually Non-Monogamous Relationships as a Function of Moral Foundations and Disgust Sensitivity
No full textIn two experiments we demonstrate how participants perceive individuals in consensually non-monogamous relationships (e.g., polyamory) more negatively compared to those in monogamous relationships, as a function of moral foundation variables and trait-level disgust sensitivity. In Study 1, we experimentally presented participants with vignettes depicting characters in one of two relationship types (monogamous or non-monogamous), after which participants completed character judgments (ethics) and relationship impressions. Participants viewed the characters in a monogamous relationship as more ethical and having higher relationship quality, and these associations were fully mediated by perceptions of the characters as pure, loyal, caring, fair, and honest. Participants high in sensitivity to disgust also perceived the consensually non-monogamous as less ethical and having lower relationship quality compared to participants low in disgust sensitivity. In Study 2, we utilized a victim-blaming paradigm with vignettes in which a character was killed, after which participants were asked to rate who was morally culpable. Participants viewed the non-monogamous character who was killed in the story as more morally culpable, and lower in loyalty and purity, compared to the control condition in which the killed character was monogamous. We discuss these findings in terms of implications for social perception and moral judgment towards consensually non-monogamous relationships
From the Ground Up: Community-Based Participatory Research Reclaiming the Science of Lead
No full textFor decades, the dominant approach to lead poisoning has been to focus on homes affected by lead paint and to treat children who are already suffering from lead poisoning. This individualizing approach developed in the context of the defunding and deregulation of government agencies in the 1980s. In recent years, however, community–academic partnerships have reframed lead as an environmental issue produced by the development of the lead industry in the twentieth century and connected to overlapping histories of exploitation, discrimination, and inaction. These community-based projects have contributed to shifting research agendas (by emphasizing historical analysis and the study of the soil and dust), achieved policy changes (with a focus on community-level solutions), and built networks and solidarity with groups advocating for climate justice, tenant organizing, and food security
Tale or Reality about Two Asian Regions
Get PDFBy 2024, South Asia will be the next region for economic growth. Reaching this expectation may be dependent on significant changes. In 1970, the per capita gross domestic product for the countries of South Asia and Southeast Asia was similar. Except for Singapore, the countries of Southeast Asia suffered from low levels of education, low participation of women in the workforce, poor infrastructure, low inward flows of FDI, and high barriers to trade. The Vietnam War encompassed Vietnam, Cambodia, and Laos. Indonesia was controlled by Suharto, and Burma (Myanmar) was among the poorest countries outside of sub-Saharan Africa. Fast forward five decades, and the countries of Southeast Asia have undergone dramatic change and have outperformed South Asia. The recent success of South Asia is the product of starting from a low level of performance during the pandemic rather than significant structural changes. For South Asia, replicating the performance of Southeast Asia will depend on removing cultural, regulatory, social, and economic barriers. This study identifies gender disparities, policy barriers, and a lack of regional cooperation as critical hindrances to South Asia’s growth.https://digitalcommons.chapman.edu/business_books/1014/thumbnail.jp
Mitigation Behaviors of Homeowners and Renters in the Wildland Urban Interface
Get PDFResidential development within the wildland-urban interface (WUI) has greatly expanded in the United States since the 1990s, amplifying wildfire risk by placing people and structures in greater proximity to flammable vegetation. Household wildfire mitigation actions can vary substantially by cost, knowledge required, and perceived effectiveness, but few studies have examined them separately and how their adoption varies by housing tenure in the context of wildfires. To address this gap, we surveyed residents living in WUI areas within Southern California near recent burn scars in the Santa Ana and San Bernardino Mountain ranges. Drawing on the Protection Motivation Theory and the Theory of Planned Behavior, we evaluated the factors driving the adoption of five Wildfire Mitigation Intention or Implementation (WMII) action types: fire insurance, structural retrofits, exterior minor maintenance, exterior vegetative measures, and community actions. Findings indicate that self-efficacy (perceived ability to undertake protective measures) and response efficacy (perceived effectiveness of a protective measure) are positively associated with all action types, with self-efficacy having a stronger association. Factors associated with implementation or intention to take mitigation action differed across action types. Renters reported lower levels of mitigation overall and faced greater financial and knowledge barriers. Findings stress that wildfire mitigation programs should account for how knowledge, resources, and abilities to take different WMII actions vary by housing tenure. Findings suggest that wildfire emergency officials should focus on capacity building and public education initiatives for WUI residents, with a particular focus on addressing the unique challenges renters face in high-risk areas
Remote Sensing-Based Assessment of Evapotranspiration Patterns in a UNESCO World Heritage Site Under Increasing Water Competition
Get PDFIn water-scarce regions, natural ecosystems and agriculture increasingly compete for limited water resources, intensifying stress during periods of drought. To assess these competing demands, we applied a modified PT-JPL model that incorporates the thermal inertial approach as a substitute for relative humidity (RH) in estimating soil evaporation—a method that significantly outperforms the original PT-JPL formulation in Mediterranean semi-arid irrigated areas. This remote sensing framework enabled us to quantify spatial and temporal variations in water use across both natural and agricultural systems within the UNESCO World Heritage site of Doñana. Our analysis revealed an increasing evapotranspiration (ET) trend in intensified agricultural areas and rice fields surrounding the National Park (R = 0.3), contrasted by a strong negative ET trend in wetlands (R \u3c −0.5). These opposing patterns suggest a growing diversion of water toward irrigation at the expense of natural ecosystems. The impact was especially marked during droughts, such as the 2011–2016 period, when precipitation declined by 16%. In wetlands, ET was significantly correlated with precipitation (R \u3e 0.4), highlighting their vulnerability to reduced water inputs. These findings offer crucial insights to support sustainable water management strategies that balance agricultural productivity with the preservation of ecologically valuable systems under mounting climatic and anthropogenic pressures typical of semi-arid Mediterranean environments
A Novel Approach to Increase Accuracy in Remotely Sensed Evapotranspiration Through Basin Water Balance and Flux Tower Constraints
Get PDFRemote sensing-derived evapotranspiration (RSET) products capture the spatiotemporal variations of evapotranspiration (ET) from field to basin scales with unprecedented details. However, their accuracy varies across RSET estimation methods and diverse hydroclimate regions. While ET modeling efforts to account for biophysical processes and controlling parameters have made good progress in recent years, a parallel approach of integrating in-situ ET with RSET could reduce biases in RSET products. Basin water balance ET (WBET) and flux tower ET are widely applied to evaluate RSET accuracy, yet such ET measurements are rarely used for RSET bias corrections, especially for large area applications. To address this issue, we propose a novel approach: the water balance equivalence (WABE) method, which generates spatially continuous WBET for correcting biases in RSET products. The WABE method computes synthetic WBET by integrating observed WBET and flux tower-derived FLUXCOM ET, which fills the spatial gaps of observed WBET and generates a spatially continuous WBET dataset. Synthetic WBET (2002–2015 annual average) of eight-digit hydrologic unit code (HUC8) basins across the conterminous United States (CONUS), constituting 44 % (887 out of 2035 basins) of CONUS basins, was determined within 2.0 % (RMSE = 12 %) of observed WBET at CONUS and between 1–12 % (RMSE = 3–33 %) across 18 regions in CONUS. With WABE-based bias corrections, the overall annual bias of RSET decreased from 10 % (RMSE = 34 %) to 6 % (RMSE = 26 %) across 37 flux tower sites. The WABE method offers a new approach for RSET accuracy improvement and shows great promise for large area implementations with a potential to yield substantial benefits for building accurate basin water budgets and water management decisions
Exploring Human-Centered Principles to Improve Lecture Slides
Get PDFAs a university emphasizing student participation and attention, lectures are central to the educational experience at Chapman. However, slide-based lectures can widely vary in quality and approach. Considering various debunkings of learning styles over the years, it seems more difficult than ever to understand how to most effectively teach students. Effective use of computerized tools has thus become increasingly important as the pace of change continues to increase. Yet, research is available on the effectiveness of teaching methods that can provide guidelines for instructors. With increasingly connected and capable devices at our fingertips, it is imperative to both use the technology to our advantage and cut through distractions by creating engaging material. Using a human, research-based approach, this work aims to optimize the time and attention of students and instructors, precious resources that demand careful consideration. Employing research focused on human factors such as habituation, accessibility, and cognitive load theory, current faculty slides were analyzed. Quantitative and qualitative approaches were taken to discover trends in slide design and to identify areas of improvement. For instance, when surveyed, a majority of faculty respondents indicated a desire to create more engaging slides in less time. Additionally, slides were analyzed for readability, visual layout, and accessibility. Strategies to make the development of slides more effective and efficient are proposed, along with directions for future research and development
Peptide-Based Inorganic Nanoparticles as Efficient Intracellular Delivery Systems
No full textBackground/Objectives: Peptide-based inorganic nanoparticles (PINPs) have emerged as promising candidates for intracellular delivery due to their unique structural and functional attributes. These hybrid nanostructures combine the high surface area and tunable optical/magnetic properties of metal cores (e.g., Au, Ag, Fe3O4) with the biocompatibility, targeting specificity, and responsive behavior of peptides. In particular, peptides with amphipathic or cell-penetrating features could facilitate efficient transport of molecular cargos across cellular membranes while enabling stimulus-responsive drug release in target tissues. Methods: We review key synthesis methods (especially green, peptide-mediated one-pot approaches), functionalization strategies (e.g., thiol-gold bonds, click chemistries), and characterization techniques (TEM, DLS, FTIR, etc.) that underpin PINP design. In addition, we highlight diverse peptide classes (linear, cyclic, amphipathic, self-assembling) and their roles (targeting ligands, capping/stabilizing agents, reducing agents) in constructing multifunctional nanocarriers. Results: The prospects of PINPs are considerable: they enable targeted drug delivery with imaging/theranostic capability, improve drug stability and cellular uptake, and harness peptide programmability for precision nanomedicine. However, challenges such as in vivo stability, immunogenicity, and standardization of evaluation must be addressed. Conclusions: Overall, PINPs represent multifunctional platforms that could significantly advance drug delivery and diagnostic applications in the future