Distinctive Capacity Research Articles

Genomic Characterization of Bacillus sp. THPS1: A Hot Spring-Derived Species with Functional Features and Biotechnological Potential

Bacillus sp. THPS1 is a novel strain isolated from a high-temperature hot spring in Thailand, exhibiting distinctive genomic features that enable adaptation to an extreme environment. This study aimed to characterize the genomic and functional attributes of Bacillus sp. THPS1 to understand its adaptation strategies and evaluate its potential for biotechnological applications. The draft genome is 5.38 Mbp with a GC content of 35.67%, encoding 5606 genes, including those linked to stress response and sporulation, which are essential for survival in high-temperature conditions. Phylogenetic analysis and average nucleotide identity (ANI) values confirmed its classification as a distinct species within the Bacillus genus. Pangenome analysis involving 19 others closely related thermophilic Bacillus species identified 1888 singleton genes associated with heat resistance, sporulation, and specialized metabolism, suggesting adaptation to nutrient-deficient, high-temperature environments. Genomic analysis revealed 12 biosynthetic gene clusters (BGCs), including those for polyketides and non-ribosomal peptides, highlighting its potential for synthesizing secondary metabolites that may facilitate its adaptation. Additionally, the presence of three Siphoviridae phage regions and 96 mobile genetic elements (MGEs) suggests significant genomic plasticity, whereas the existence of five CRISPR arrays implies an advanced defense mechanism against phage infections, contributing to genomic stability. The distinctive genomic features and functional capacities of Bacillus sp. THPS1 make it a promising candidate for biotechnological applications, particularly in the production of heat-stable enzymes and the development of resilient bioformulations.

The protumorigenic enzyme GPAT2 inhibits arachidonic acid-triggered apoptosis in breast cancer

BackgroundCancer is a significant health challenge and the leading cause of mortality globally. Tumor cells use multiple mechanisms to acquire their distinctive capacity for uncontrolled proliferation, one of which is the evasion of apoptosis. It has been shown that in breast, colon, and liver cancer, evasion of apoptosis is associated with the overexpression of enzymes that metabolize arachidonic acid (AA) because free AA is a strong inducer of apoptosis. Glycerol−3-phosphate acyltransferase 2 (GPAT2) is a key enzyme in AA metabolism and is highly expressed in breast and colon cancer, where it promotes the development of essential tumor features.MethodsIn this work, a model of GPAT2 silencing in the human breast cancer-derived cell line MDA-MB-231 was used, and the cells were exposed to exogenous AA. The role of GPAT2 in AA-induced cell death was studied using MTT and TUNEL assays and measurements of caspase activity. The underlying molecular mechanism of cell death was assessed by qRT‒PCR.ResultsThe results showed that AA reduced cell viability only in GPAT2-silenced cells, and that this cell death was a consequence of an apoptotic process involving BNIP3 overexpression. Additionally, it was demonstrated that GPAT2 silencing triggered a compensatory mechanism by overexpressing other genes involved in AA utilization for eicosanoid biosynthesis.ConclusionsWe concluded that GPAT2 expression is necessary to prevent AA-induced apoptotic cell death in MDA-MB-231 cells and that the overexpression of other AA-metabolizing genes is not sufficient to compensate for the lack of GPAT2 and prevent apoptosis.

When the world gets worse: Form and feeling in Australian climate fiction

In a political context of climate inaction, Australian fiction writers have increasingly focused on the emergency; drawing attention to how the political and environmental processes underway might play out and exploring attendant emotions. The novel form – with its foregrounding of private feelings and individual agency, and its historical alignment with the development of the extractive capitalism it may wish to critique – occupies an ambivalent position as a tool to bring about change. If the task is to refigure the social imaginary towards interconnection with all forms of life, is the novel an inadequate means of social engagement? I hope to make the case – by referencing debates in climate change literature and through discussion of Scary Monsters by Michelle de Kretser (2021) and This Devastating Fever by Sophie Cunningham (2022) – that writers are using the distinctive capacities of the novel to think through contemporary challenges. These novels, distinct in tone and narrative content, both treat climate change as inextricable from other forces – such as colonialism and misogyny – and emphasise interconnectedness with other beings. Through a commitment to play, via formal experimentation and humour, they help readers to engage with the intellectual and emotional challenges of a changing world.

LLM4THP: a computing tool to identify tumor homing peptides by molecular and sequence representation of large language model based on two-layer ensemble model strategy

Tumor homing peptides (THPs) have a distinctive capacity to specifically attach to tumor cells, providing a promising approach for targeted cancer treatment and detection. Although THPs have the potential for significant impact, their detection by conventional methods is both time-consuming and expensive. To tackle this issue, we provide LLM4THP, an innovative computational approach that utilizes large language models (LLMs) to quickly and effectively detect THPs. LLM4THP utilizes two protein LLMs, ESM2 and Prot_T5_XL_UniRef50, to encode peptide sequences. This allows for the capture of complex patterns and relationships within the peptide data. In addition, we utilize inherent sequence characteristics such as Amino Acid Composition (AAC), Pseudo Amino Acid Composition (PAAC), Amphiphilic Pseudo Amino Acid Composition (APAAC), and Composition, Transition, and Distribution (CTD) to improve the representation of peptides. The RDKitDescriptors feature representation approach transforms peptide sequences into molecular objects and computes chemical characteristics, resulting in enhanced THP identification. The LLM4THP ensemble strategy incorporates various features into a two-layer learning architecture. The first layer consists of LightGBM, XGBoost, Random Forest, and Extremely Randomized Trees, which generate a set of meta results. The second layer utilizes Logistic Regression to further refine the identification of sequences as either THP or non-THP. LLM4THP exhibits exceptional performance compared to the most advanced methods, showcasing enhancements in accuracy, Matthew’s correlation coefficient, F1 score, area under the curve, and average precision. The source code and dataset can be accessed at the following URL: https://github.com/abcair/LLM4THP.

Tailoring highland barley bran arabinoxylans: Insights into composition, structure, and functional properties

Highland barley bran (HBB) stands as an underutilized source of arabinoxylans (AXs), presenting promising prospects for various applications. This study focuses on the isolation of four different AXs (S20, S40, S60, S80) from HBB using alkali extraction and gradient alcohol precipitation. These AXs exhibited diverse purity (56.47%–80.92%), monosaccharide compositions (A/X:0.47–0.96), and molecular weights (Mw) (173.5–498.2 kDa) of different AXs, along with different microstructural variations, amorphous qualities, and thermal stability. Rheological analyses demonstrated their shear-thinning behavior and distinctive gel-forming capacities, with S20 exhibiting superior viscosity and gel-forming ability. Notably, all four AXs demonstrate notable DPPH and ABTS radical scavenging capacities, with S80 demonstrating the highest antioxidant potency. Correlation analyses highlighted connections between molecular weight, branching degree, and rheological and antioxidant properties of AXs. Among different AXs, S20, with its low branching degree (0.47) and high molecular weight (390.4 kDa), exhibited significant viscosity, suggesting its suitability as a natural thickener in food processing. Conversely, S80, characterized by its low molecular weight (173.5 kDa), high branching degree (0.96), and potent antioxidant activity, holds promise as a natural antioxidant in functional foods. This study provides crucial insights for tailoring AX applications, unlocking the potential for the valorization of HBB in diverse scenarios.

Apocynin alleviates thioacetamide-induced acute liver injury: Role of NOX1/NOX4/NF-κB/NLRP3 pathways

The liver has a distinctive capacity to regenerate, yet severe acute injury can be life-threatening if not treated appropriately. Inflammation and oxidative stress are central processes implicated in the pathophysiology of acute livery injury. NOX isoforms are important enzymes for ROS generation, NF-κB and NLRP3 activation, its inhibition could be vital in alleviating acute liver injury (ALI). Here in our study, we used apocynin, a natural occurring potent NOX inhibitor, to exploreits potential protective effect against thioacetamide (TAA)-induced ALI through modulating crucial oxidative and inflammatory pathways. Rats were injected once with TAA (500 mg/kg/i.p) and treated with apocynin (10 mg/kg/i.p) twice before TAA challenge. Sera and hepatic tissues were collected for biochemical, mRNA expression, western blot analysis and histopathological assessments. Pretreatment with apocynin improved liver dysfunction evidenced by decreased levels of aminotransferases, ALP, GGT and bilirubin. Apocynin reduced mRNA expression of NOX1 and NOX4 which in turn alleviated oxidative stress, as shown by reduction in MDA and NOx levels, and elevation in GSH levels andcatalase and SOD activities. Moreover, apocynin significantly reduced MPO gene expression. We also demonstrate that apocynin ameliorated inflammation through activating IκBα and suppressing IKKα, IKKβ, NF-κBp65 and p-NF-κBp65, IL-6 andTNF-α. Additionally, apocynin potentiated the gene expression of anti-inflammatory IL-10 and reduced levels of hepatic NLRP3, Caspase-1 and IL-1β. These results suggest that apocynin protects against ALI in association with the inhibition of NOX1 and NOX4 and regulating oxidative and inflammatory pathways.

Unveiling the Dynamic Interplay between Cancer Stem Cells and the Tumor Microenvironment in Melanoma: Implications for Novel Therapeutic Strategies.

Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are a small subpopulation of cells in different tumors, including melanoma, endowed with distinctive capacities of self-renewal and differentiation into bulk tumor cells. Melanoma CSCs are characterized by the expression of specific biomarkers and intracellular pathways; moreover, they play a pivotal role in tumor onset, progression and drug resistance. In recent years, great efforts have been made to dissect the molecular mechanisms underlying the protumor activities of melanoma CSCs to provide the basis for novel CSC-targeted therapies. Herein, we highlight the intricate crosstalk between melanoma CSCs and bystander cells in the tumor microenvironment (TME), including immune cells, endothelial cells and cancer-associated fibroblasts (CAFs), and its role in melanoma progression. Specifically, we discuss the peculiar capacities of melanoma CSCs to escape the host immune surveillance, to recruit immunosuppressive cells and to educate immune cells toward an immunosuppressive and protumor phenotype. We also address currently investigated CSC-targeted strategies that could pave the way for new promising therapeutic approaches for melanoma care.

Liver regeneration after injury: Mechanisms, cellular interactions and therapeutic innovations.

The liver possesses a distinctive capacity for regeneration within the human body. Under normal circumstances, liver cells replicate themselves to maintain liver function. Compensatory replication of healthy hepatocytes is sufficient for the regeneration after acute liver injuries. In the late stage of chronic liver damage, a large number of hepatocytes die and hepatocyte replication is blocked. Liver regeneration has more complex mechanisms, such as the transdifferentiation between cell types or hepatic progenitor cells mediated. Dysregulation of liver regeneration causes severe chronic liver disease. Gaining a more comprehensive understanding of liver regeneration mechanisms would facilitate the advancement of efficient therapeutic approaches. This review provides an overview of the signalling pathways linked to different aspects of liver regeneration in various liver diseases. Moreover, new knowledge on cellular interactions during the regenerative process is also presented. Finally, this paper explores the potential applications of new technologies, such as nanotechnology, stem cell transplantation and organoids, in liver regeneration after injury, offering fresh perspectives on treating liver disease.

Past materials, past minds: The philosophy of cognitive paleoanthropology

AbstractThe philosophy of cognitive paleoanthropology involves three related tasks: (1) asking what inferences might be drawn from the paleontological and archaeological records to past cognition, behavior and culture; (2) constructing synthetic accounts of the evolution of distinctive hominin capacities; (3) exploring how results from cognitive paleoanthropology might inform philosophy. We introduce some distinctive cognitive paleoanthropological inferences and discuss their epistemic standing, before considering how attention to the material records and the practice of paleoanthropology can inform and transform philosophical approaches.

Elongation capacity of polyunsaturated fatty acids in the annelid Platynereis dumerilii.

Elongation of very long-chain fatty acid (Elovl) proteins plays pivotal functions in the biosynthesis of the physiologically essential long-chain polyunsaturated fatty acids (LC-PUFA). Polychaetes have important roles in marine ecosystems, contributing not only to nutrient recycling but also exhibiting a distinctive capacity for biosynthesizing LC-PUFA. To expand our understanding of the LC-PUFA biosynthesis in polychaetes, this study conducted a thorough molecular and functional characterization of Elovl occurring in the model organism Platynereis dumerilii. We identify six Elovl in the genome of P. dumerilii. The sequence and phylogenetic analyses established that four Elovl, identified as Elovl2/5, Elovl4 (two genes) and Elovl1/7, have putative functions in LC-PUFA biosynthesis. Functional characterization confirmed the roles of these elongases in LC-PUFA biosynthesis, demonstrating that P. dumerilii possesses a varied and functionally diverse complement of Elovl that, along with the enzymatic specificities of previously characterized desaturases, enables P. dumerilii to perform all the reactions required for the biosynthesis of the LC-PUFA. Importantly, we uncovered that one of the two Elovl4-encoding genes is remarkably long in comparison with any other animals' Elovl, which contains a C terminal KH domain unique among Elovl. The distinctive expression pattern of this protein in photoreceptors strongly suggests a central role in vision.

Ultralight Flexible Collagen Fiber Based Aerogels Derived from Leather Solid Waste for High Electromagnetic Interference Shielding.

Designing and developing high-performance shielding materials against electromagnetic interference is of utmost importance due to the rapid advancement of wireless telecommunication technologies. Such materials hold both fundamental and technological significance. A three-stage process is presented for creating ultralight, flexible aerogels from biomass to shield against electromagnetic interference. Collagen fibers sourced from leather solid waste are used for: (i) freeze-drying preparation of collagen fibers/poly(vinyl alcohol) (PVA) aerogels, (ii) adsorption of silver nanowires (AgNWs) onto collagen fiber/PVA aerogels, and (iii) Hydrophobic modification of collagen fiber/PVA/AgNWs aerogels with 1H, 1H, 2H, 2H-perfluorodecyltriethoxysilane (POTS). Scanning electron microscopy studies reveal that an interweaving of AgNWs and collagen fiber/PVA porous network has formed a conductive network, exhibiting an electrical conductivity of 103 S·m-1. The electromagnetic interference shielding effectiveness reached more than 62 dB, while the density was merely 5.8 mg/cm3. The collagen fiber/PVA/AgNWs/POTS aerogel displayed an even better electromagnetic shielding efficiency of 73 dB and water contact angle of 147°. The study results emphasize the distinctive capacity of leather solid waste to generate cost-effective, ecofriendly, and highly efficient electromagnetic interference shielding materials.

Advancing Diagnostics: Evaluating the Potential of Nanoparticle-Based Immunoassays as PCR Alternatives for Disease Confirmation

Abstract: In diagnostic technologies, searching for quick, accurate, and cost-efficient ways to confirm diseases has prompted the investigation of alternative methodologies to classic PCR-based tests. This article delves into the growing field of nanoparticle-based immunoassays, offering a comprehensive evaluation of their potential as viable alternatives to PCR for disease diagnostics. We discuss the basic principles of nanoparticle-based immunoassays, highlighting their distinctive capacity to combine the specialized binding characteristics of antibodies with the improved detection capacities of nanoparticles. The article compares the performance attributes of nanoparticle-based immunoassays compared to PCR, focusing on sensitivity, specificity, and detection speed. We further delve into a novel diagnostic technology, immuno-PCR, which integrates the strengths of immunoassays and PCR techniques. Healthcare systems and stakeholders must comprehend and implement novel diagnostic procedures emphasizing accuracy and sensitivity as the diagnostic landscape advances globally. This review contributes to the advancement of diagnostics by synthesizing current research and suggesting future directions for development. It highlights the transformative potential of current and emerging methods in shaping the future of disease diagnostics.

Review on functionalized pectin films for active food packaging

AbstractOwing to environmental distresses and growing demands for food safety, biopolymers have found noble applications in food packaging films as they are biodegradable, biocompatible and non‐toxic. Pectin, polysaccharide based biomass was considered a promising substrate in fabricating polymeric films because of its advantages concerning film‐forming ability, low cost, bioactivity, compatibility with other polymers with a distinctive oxygen barrier capacity, which helps in improving shelf life of commodities. Introducing active agents into the packaging films focus to prolong the shelf life and preserve the sensorial quality and safety of packaged foods devoid of contamination. Antimicrobial agents or secondary metabolites derived from plants and fungi are perceived as promising natural bio‐active agents integrated into films to prevent microbial deterioration. Pectin has been greatly utilized in active packaging films incorporated with natural additives such as essential oils, nanoparticles, free fatty acids and phenolic compounds that inhibit/retard the growth of major foodborne pathogens. The above‐mentioned functionalization of pectin films with bio‐active compounds enhanced microbial resistance and contemporarily influenced the mechanical strength and barrier properties of the film. This review is intended to focus on the background of pectin, its source and the utilization of pectin in active packaging films, and the types and method of incorporation of natural compounds. Specific emphasis has been given to the types of bioactive compounds incorporated into pectin films and their impact on the functional properties of the films. This review will benefit researchers in exploring innovative methods of incorporating bioactive compounds into pectin‐based films.

Rx Metaphysics

Recent research on the structure of life-narratives and narrative identity suggests that meaning-making and narrative coherence are predictive of adjustment and resilience. I argue that the metaphysical presumptions operative in a client’s worldview are fundamental elements of meaning-making, and that these presumptions contribute to the life-narrative’s distinctive capacity to guide us through life-challenges. This application of metaphysical methodology to client worldviews represents a systematic extension of logic-based therapy. In this paper, I articulate a conceptual framework for worldview analysis and reconstruction using the resources of logic, metaphysics, and epistemology. I draw particularly on C. G. Jung’s concept of Auseinandersetzung, often inadequately translated as “working through,” John Dewey’s notion of “reconstruction in philosophy,” and José Ortega y Gasset’s exploration of worldview as a “basic orientation” in the world. I provide brief illustrations of this framework in practice, and I conclude with some observations about indications and contraindications for worldview reconstruction as a modality of philosophical practice.

A metal-organic framework-integrated composite for piezocatalysis-assisted tumour therapy: design, related mechanisms, and recent advances.

With the growing need for more effective tumour treatment, piezocatalytic therapy has emerged as a promising approach due to its distinctive capacities to generate ROS through stress induction and regulate the hypoxic state of the TME. MOF-based piezocatalysts not only possess the benefits of piezocatalysis but also exhibit several advantages associated with MOFs, such as tunable pore size, large specific surface area, and good biocompatibility. Therefore, they are expected to become a powerful promoter of piezocatalytic therapy. This review elaborates on the fundamental principles of piezocatalysis and summarises recent advances in the piezocatalytic therapy and combination therapies of tumours, generalising the strategies for constructing piezocatalytic systems based on MOFs. Finally, the challenges confronted and future opportunities for the design and application of piezocatalytic MOF anticancer systems have been discussed.

Unraveling Multiple Pathways of Electron Donation from Phenolic Moieties in Natural Organic Matter.

Natural organic matter (NOM) exhibits a distinctive electron-donating capacity (EDC) that serves a pivotal role in the redox reactions of contaminants and minerals through the transformation of electron-donating phenolic moieties. However, the ambiguity of the molecular transformation pathways (MTPs) that engender the EDC during NOM oxidation remains a significant issue. Here, MTPs that contribute to EDC were investigated by identifying the oxidized products of phenolic model compounds and NOM samples in direct or mediated electrochemical oxidation (DEO or MEO, respectively) using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). It was found that the oxidation of newly formed phenolic-OH (ArOH) and the oxidative coupling reaction of the phenoxy radical are the main MTPs that directly contribute to EDC, in addition to the transformation of hydroquinones to quinones. Notably, the oxidative coupling reaction of ArOH contributed at least 22-42% to the EDC. Ferulic acid-like structures can also directly contribute to EDC by incorporating H2O into their acrylic substituents. Furthermore, the opening of C rings can indirectly attenuate the EDC through structural alterations in the electron-donating process of NOM. Decarboxylation can either weaken or enhance the EDC depending on the structure of the phenolic moieties in NOM. These findings suggest that the EDC of NOM is a comprehensive result of multiple NOM MTPs, involving not only ArOH oxidation but also the addition of H2O to olefinic bonds and bond-breaking reactions. Our work provides molecular evidence that aids in the comprehension of the multiple EDC-associated transformation pathways of NOM.

Research Progress of Piriformospora indica in Improving Plant Growth and Stress Resistance to Plant.

Piriformospora indica (Serendipita indica), a mycorrhizal fungus, has garnered significant attention in recent decades owing to its distinctive capacity to stimulate plant growth and augment plant resilience against environmental stressors. As an axenically cultivable fungus, P. indica exhibits a remarkable ability to colonize varieties of plants and promote symbiotic processes by directly influencing nutrient acquisition and hormone metabolism. The interaction of plant and P. indica raises hormone production including ethylene (ET), jasmonic acid (JA), gibberellin (GA), salicylic acid (SA), and abscisic acid (ABA), which also promotes root proliferation, facilitating improved nutrient acquisition, and subsequently leading to enhanced plant growth and productivity. Additionally, the plant defense system was employed by P. indica colonization and the defense genes associated with oxidation resistance were activated subsequently. This fungus-mediated defense response elicits an elevation in the enzyme activity of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and, finally, bolsters plant tolerance. Furthermore, P. indica colonization can initiate local and systemic immune responses against fungal and viral plant diseases through signal transduction mechanisms and RNA interference by regulating defense gene expression and sRNA secretion. Consequently, P. indica can serve diverse roles such as plant promoter, biofertilizer, bioprotectant, bioregulator, and bioactivator. A comprehensive review of recent literature will facilitate the elucidation of the mechanistic foundations underlying P. indica-crop interactions. Such discussions will significantly contribute to an in-depth comprehension of the interaction mechanisms, potential applications, and the consequential effects of P. indica on crop protection, enhancement, and sustainable agricultural practices.

The great reset: Could Henry George be the antidote to the world economic forum?

AbstractThe Great Reset, as envisioned by the World Economic Forum, involves another step in the evolution toward a system of close cooperation between the national security state and key corporations that can manage information and limit dissent. In return for allowing state control of many facets of personal life, the state offers to take care of the needs of citizens who are in compliance with their assigned place in the social order. Already citizens have given up considerable autonomy and allow constant surveillance, mostly through smartphones. The only true alternative to a paternalist trajectory is to imagine a different kind of great reset, one in which society is organized around genuine principles of self‐governance and self‐reliance. This idea can be traced to the American social theorist Henry George and further back to roots in ancient China of the philosophy of wu wei. The main idea is that higher‐order systems are designed to offer both stability and freedom to lower‐order systems. Rather than trying to abolish an intrusive state apparatus, the aim is to create systems that obviate the need for a welfare state or a warfare state. This is a tall order to fill, but it is worth striving for as a way of preserving the distinctive human capacities for both individual initiative and social bonding. Unless millions work to create a decentralized world order, we are almost surely doomed to endure a technocratic future of increasing surveillance and management of our private lives.

Experiences of Faith-Based Organizations as Key Stakeholders in Policy Responses to Human Trafficking

Faith-based organizations (FBOs) are substantially involved in the anti-human trafficking movement. Yet, limited research is available on their crucial roles in the field. This study explored their input in anti-trafficking policy implementation in the US by examining their motivations to engage in anti-human trafficking work, their distinctive competencies as stakeholders, and their experiences and challenges in providing anti-human trafficking services. A purposive sample of 16 leaders from 14 FBOs with anti-human trafficking work experience was recruited. A semi-structured interview guide was used to collect data. A thematic analysis of the data was conducted. The findings showed that FBOs have experience in various aspects of prevention, protection, and even assistance in prosecuting human trafficking cases and at multiple levels of intervention. The distinctive capacities of FBOs for policy advocacy, training, and housing services for trafficking survivors provide a glimpse of their leading roles in human trafficking policy implementation. Operating primarily outside public funding allows FBOs to develop short-term and long-term services for trafficking survivors without time constraints. The FBOs in the study reported using a non-discriminatory, survivor-centered, and trauma-informed approach in their anti-human trafficking service delivery. All the respondents in the study concurred that efforts by any FBOs to convert trafficking survivors to a particular faith are unethical and counterproductive. The implications for practice, policy implementation, and research are discussed.

Love, Knowledge, and Freedom in Pleasantville, Religious Scripture, and Wider Western Literature

Abstract Love has long been extolled as a route to human moral and spiritual progress and fulfilment, not only in much past religious literature and narrative but in the more recent work of writers such as the philosopher and novelist Iris Murdoch. In such texts, however, the sentiment (or virtue) of love is clearly more than just blind or brute passion and presupposes distinctive human capacities for knowledge and free agency. That said, the relationship between knowledge and (right or virtuous) agency seems highly problematic or ambivalent on many traditional (perhaps most notably Christian) religious conceptions. This paper addresses such issues and complexities via some exploration of Genesis and the modern movie Pleasantville—with further aid from literary works of Shakespeare, Blake, Heinlein, and others—to the end of a more realistic view of human love and its moral and spiritual implications.