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Multiparametric cytotoxicity assessment: The effect of gold nanoparticle functionalization on SKOV3 ovarian carcinoma cell death
No full textGold nanoparticles (AuNP) are promising anti-cancer agents because of their modifiable properties and high biocompatibility. This study used multiple parallel analyses to investigate the cytotoxic properties of 5 nm AuNP conjugated to four different ligands with distinct surface chemistry: polyethylene glycol (PEG), trimethylammonium bromide (TMAB), 4-dimethylaminopyridine (DMAP), and carboxyl (COOH). We used a range of biochemical and high-content microscopy methods to evaluate metabolic function, oxidative stress, cell health, cell viability, and cell morphology in SKOV3 ovarian cancer cells. Each AuNP displayed a distinct cytotoxicity profile. All AuNP species assessed exhibited signs of dose-dependent cytotoxicity when morphology, clonogenic survival, lysosomal uptake, or cell number were measured as the marker of toxicity. All particles except for AuNP-COOH increased SKOV3 apoptosis. In contrast, AuNP-TMAB was the only particle that did not alter metabolic function or to induce significant signs of oxidative stress. These results demonstrate that AuNP surface chemistry impacts the magnitude and mechanism of SKOV3 cell death. Together, these findings reinforce the important role for multiparametric cytotoxicity characterization when considering the utility of novel particles and surface chemistries.This is an Accepted Manuscript of an article published by Taylor & Francis in Nanotoxicology on July 5, 2022, available at: http://www.tandfonline.com/10.1080/17435390.2022.2095312
Hybrid AI models for variable star classification
Full text linkThe classification of variable stars is an important problem for many people in the astronomy community. Variable stars provide a unique means to probe the internal structure of distant stars. The process of classifying these stars presents itself perfectly to machine learning. This paper proposes a hybrid model, combining the feature extraction capabilities of a convolutional neural network with the classification power of a non-parametric kernel density estimation paired with a naive-Bayes classifier. On classification tasks with 15 types of variable stars, the model achieves roughly 77% accuracy, placing it in line with the average performance seen throughout the literature. The hybrid model is special, though, in that it achieves this accuracy with comparatively less training time, a smaller sample size, and more specific classes
Characterizing nutrient-activation of orphan and lipid metabolism-related G protein-coupled receptors
Full text linkNutrients and food additives serve as energy sources or non-nutritive flavour enhancers for organisms. Advances in nutrient-sensing mechanisms and the discovery of the reciprocal relationship between metabolism and intracellular pathways have identified some nutritive and non-nutritive food components, namely amino acids (AAs) and non-nutritive sweeteners (NNSs), as ligands for G protein-coupled receptors (GPCRs). For example, AAs act as ligands for mGluRs, multiple class C GPCRs and the class A orphans GPR142 and GPR139. Meanwhile, NNSs of markedly different structures have been shown to activate the sweet taste receptors T1R2/T1R3. The consumption of AAs aids in managing food intake and glucose homeostasis, although the mechanisms underlying these metabolic benefits remain unclear. However, a recent study identified an intestinal trafficking mechanism of individual AAs leading to the activation of an AA-sensing GPCR, suggesting that GPCRs play a larger role in nutrient signalling than once thought. Food products containing NNSs have become increasingly popular over the past few decades to provide powerful sweetness, in part through the activation of the sweet taste receptors T1R2/T1R3, without the added calories. Despite being considered metabolically inert, the consumption of NNSs has been linked to an increased risk of obesity, type 2 diabetes, and metabolic syndrome with suggested off-target signalling through GPCRs independent of T1R2/T1R3. Ligand identification is critical in understanding GPCR function; as a result, we used a high throughput approach quantifying GPCR activation to identify novel nutrient-GPCR interactions. This approach was applied to two experimental questions 1) to what extent do AAs activate orphan and lipid metabolism-related GPCRs, and 2) do NNSs elicit off-target signalling events through interactions with GPCRs? Both projects primarily measured b-arrestin recruitment and used a panel of in vitro luciferase signalling reporters. Herein, we discovered that the AA L-phenylalanine (Phe) is a promiscuous endogenous ligand, significantly activating 148 class A GPCRs. Additionally, we found that the NNS sucralose increases the activity of the constitutively active orphan GPCR GPR52. These observations are the first to identify the widespread binding capacity of Phe through GPCRs and a GPCR other than the taste receptors as a target for sucralose. This study provides evidence of the interplay between metabolite sensing and the GPCR signalling network and may potentially inform pharmacological approaches to predict novel agonists or off-target effects
Defining revolution: An examination of Marx and his works
Full text linkThroughout his writings, Karl Marx speaks of revolution, and how this will allow for a transition towards a communist society. However, due to the language he uses, it has been easy for some people to misunderstand what he means by the term ‘revolution.’ Indeed, this has led some people to misrepresent his philosophy, citing Marx as a supporter of coup d’états and political revolutions when in reality he supports a more transformational process of social revolution. Although Marx uses the term revolution, there are many places in his work where he clarifies that he is referring to social revolution, not political revolution. The following sections will illustrate what Marx says on this subject by examining several of his works and by using textual evidence to determine his true opinion and philosophy on this issue. Several of Marx’s texts will be examined, ranging from On the Jewish Question to The Civil War in France
Synthesis and characterization of novel iminopyridinium platinum(II) coordination complexes as potential chemotherapeutic drugs
Full text linkThis study focuses on the synthesis and characterization of five novel iminopyridinium ligands using an appropriate alkyl amine and 6-methyl-2-pyridinecarboxaldehyde. Synthesis of four platinum (II) complexes were achieved by chelating the appropriate ligand to [PtCl2(η2-coe)]2 (coe = cis-cyclooctene). The ligands were characterized using 1H, 13C{1H} nuclear magnetic resonance (NMR) and Fourier-Transformed Infrared spectroscopy (FT-IR). The complexes were characterized using 1H, 13C{1H} NMR and FT-IR spectroscopy and melting point analysis. An X-ray diffraction study was performed on dichloro-[(6-methylpyridin-2-yl)methylene)hexan-1-amine] platinum (II). Elemental analysis was also conducted on C1 and C2, however the data was inconclusive. Prospective work includes acquiring a more conclusive elemental analysis on all complexes and conducting bioactivity and cytotoxicity test on the synthesized complexes
Academic success, persistence and satisfaction with online learning during a global pandemic
Full text linkOnline learning has become much more common over the last few years, but it became particularly prevalent when the COVID-19 pandemic prevented in person course instruction at universities and colleges. Despite the research on online learning, there is still a great deal of uncertainty that surrounds the components that contribute to effective and productive online learning. The purpose of the present investigation was to examine the relationship between past predictors of online learning in the context of a global pandemic. A total of 119 undergraduate students completed measures on self-efficacy, preparedness for online learning, lifestyle suitability, persistence, satisfaction, and the impact of COVID-19 on online learning. As expected, correlations and regressions showed that self-efficacy was positively associated with the three outcomes of academic success, persistence, and satisfaction. Despite being correlated, preparedness for online learning was not a significant predictor of academic success, however, it was a significant predictor of satisfaction. Similarly, lifestyle suitability did not predict persistence, but did show correlations that suggested trends for future research. Lastly, correlations showed that the impact of COVID-19 was negatively associated with many of the predictors, providing possible trends that require further investigation. Overall, this study highlights the importance of further examining the relationship between online learning predictors and the impact of the pandemic, but also suggests directions for institutions, professors, and students to take to improve future online learning outcomes
The undermining effect of sucrose reinforcement on automatically reinforced operant wheel running in rats
Full text linkThe undermining effect can be defined as a decrease in levels of intrinsic motivation for a behaviour as a consequence of the delivery and subsequent removal of a contingent extrinsically-motivating reward. A well-documented phenomenon in humans, the present study investigated the potential presence of an undermining effect of extrinsic sucrose reinforcement on intrinsically motivated (automatically-reinforced) operant wheel running in eight female Long-Evans rats. In each session, rats ran for 20 min prior to and following operant wheel running on a fixed interval (FI) 60-s schedule. Across three conditions, water, sucrose, and water were delivered as outcomes for operant wheel running on the FI 60-s schedule. No undermining effect was observed for wheel running on the FI 60-s schedule following the removal of sucrose; nor was there a decrease in running during the 20-min post-operant running period. However, wheel running during the 20 min period prior to operant running significantly decreased. Contrary to previous findings, this result suggests that an undermining effect can occur in rats. Explanations for the presence of this effect as well as suggestions for future research investigating this effect in non-human species are discussed
Easy as ABC? Investigating storybook exposure, invented spelling and vocabulary as predictors of learning to read
Full text linkIt is known that vocabulary connects to reading and can be learned from storybook exposure, yet the question remains: will children learn to read words they are exposed to through storybooks better than words not in those books? Further, would additional teaching for vocabulary depth and/or invented spelling be beneficial? These are the primary goals of the present study. Fifty-nine kindergarten students were recruited from a local elementary school to participate in a pretest, intervention, and posttest experimental design. They were exposed to 10 nonwords in a storybook, then completed word learning and learn-to-read tasks. Invented spelling was a between-participant variable, semantic enrichment within-participant. Participants correctly identified the nonwords presented in the storybook, showing vocabulary learning via storybook exposure. Extra semantic enrichment improved word learning on tasks measuring semantic depth (i.e., comparison and definition tasks). The participants were then administered a learn-to-read task, and the results showed increased learning across trials; a benefit of word exposure (control words significantly lower); an interaction between spelling and semantic enrichment- indicating a significant advantage provided by extra semantic teaching in the group that did not also spell the words. In sum, this study demonstrates that vocabulary links to learning to read on a word-specific basis, and both spelling practice and semantic enrichment further contribute to learning to read- although their beneficial effects do not appear to be additive at this early age
An assessment of orphan G-protein-coupled receptor-activation with L-phenylalanine
Full text linkAs the largest family of cell membrane receptors in the human genome, G protein-coupled receptors (GPCRs) exist in a wide variety of body tissues with a wide range of cellular signaling functions. A large subset of these GPCRs are orphans with no determined or validated endogenous ligand, which limits studies of their function and their potential pharmacological applications. Among many possible activating ligands, amino acids are able to activate some GPCRs. We hypothesized that L-Phenylalanine (L-Phe) specifically would activate numerous GPCRs, including some orphan GPCRs. To study this, a high throughput activation screen of 277 GPCRs that included 64 orphan GPCRs was conducted with a 3 mM L-Phe treatment and compared to a vehicle treatment. This L-Phe treatment significantly activated 44 of 64 orphan GPCRs, where the GPCRs GPR88, GPR45, GPR31, CXCR7, and GPR32 exhibited the highest magnitude in activation from baseline activity levels at above seven-fold. A database search showed that the tissue distributions of these orphan GPCRs were also variable, with highest GPCR expression reported in the brain and the gastrointestinal system. These findings support the idea that L-Phe is a GPCR ligand and that it potentially deorphanizes some of these orphan GPCRs. By looking at GPCR activation with L-Phe, we can gain a greater understanding of the biological implications of L-Phe beyond protein assembly