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"Baggett, David"
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Might Beauty Bolster the Moral Argument for God?
John Hare argues that Kant, in his Third Critique, offers an aesthetic argument for God’s existence that shares premises with his famous moral argument. Karl Ameriks demurs, expressing skepticism that this is so. In this paper, I stake out an intermediate position, arguing that the resources of Kant provide ingredients for an aesthetic argument, but one distinctly less than a transcendental argument for God or an entailment relation. Whether the argument is best thought of as abductive in nature, a C-inductive argument, or a Pascalian natural sign, prospects for its formulation are strong. And such an argument, for its resonances with the moral argument(s), can work well in tandem with it (them), a fact not surprising at all if Kant was right that beauty—in accordance with an ancient Greek tradition—exists in close organic relation to the good. More generally, along the way, I argue that the sea change in Kant’s studies over the last decade or so should help us see that Kant is an ally, rather than foe, to aesthetic theodicists.
Journal Article
God and Ethics
This unique and rich volume is the culmination of a Special Issue of Religions with a focus on “God and Ethics”, a topic both rich with historical significance and of special contemporary importance in light of the recent resurgence of interest in this branch of natural and philosophical theology, philosophy of religion, and religious epistemology [...]
Journal Article
Might God Help Explain Moral Knowledge?
Although owing to proper basicality, phenomenal conservatism, and deliberative indispensability our axiomatic moral judgments seem to be prima facie justified, the question of potential undercutting defeaters can pose a challenge to moral knowledge. Evolutionary debunking arguments of various stripes are one of the more recent widely discussed contenders for such a defeater. Because of the likes of Michael Ruse, Richard Joyce, and Sharon Street, such arguments have attracted much attention. Their general structure features an empirical premise according to which the process of evolution has had a significant impact on the stock of even our axiomatic moral judgments. The epistemic premise has it that if the empirical premise holds, then our moral knowledge is severely challenged if not debunked altogether, and perhaps even moral realism itself, since if our epistemic faculties can’t reliably put us in touch with objective moral truths, those truths are out of a job in our ontology. Since the most outspoken evolutionary debunkers are secularists, they somewhat understandably tend to smuggle something of a naturalistic origins thesis into their conception of evolution, thus precluding a divine guidance of the evolutionary process, which renders it a formidable challenge for them to evade the force of the debunking challenge. Unsurprisingly Ruse, Joyce, and Street all end up abandoning moral realism and any moral knowledge predicated on it. Theism, however, potentially provides a defeater-defeater against the evolutionary debunking argument(s) (if not a defeater-deflector), by rejecting the naturalistic origins thesis as a gratuitous theological add-on to which evolution need not be attached, carving out room for evolution to be a divinely guided process that may well ensure a correspondence between moral truth and at least our most nonnegotiable moral convictions.
Journal Article
Defining the condensate landscape of fusion oncoproteins
Fusion oncoproteins (FOs) arise from chromosomal translocations in ~17% of cancers and are often oncogenic drivers. Although some FOs can promote oncogenesis by undergoing liquid-liquid phase separation (LLPS) to form aberrant biomolecular condensates, the generality of this phenomenon is unknown. We explored this question by testing 166 FOs in HeLa cells and found that 58% formed condensates. The condensate-forming FOs displayed physicochemical features distinct from those of condensate-negative FOs and segregated into distinct feature-based groups that aligned with their sub-cellular localization and biological function. Using Machine Learning, we developed a predictor of FO condensation behavior, and discovered that 67% of ~3000 additional FOs likely form condensates, with 35% of those predicted to function by altering gene expression. 47% of the predicted condensate-negative FOs were associated with cell signaling functions, suggesting a functional dichotomy between condensate-positive and -negative FOs. Our Datasets and reagents are rich resources to interrogate FO condensation in the future.
Many fusion oncoproteins (FOs) form condensates, some form in the nucleus and regulate gene expression while others form in the cytoplasm and promote cell signaling. In this work, the authors report the analysis of physicochemical features to enable prediction of FO condensation behavior.
Journal Article
7-Dehydrocholesterol-derived oxysterols cause neurogenic defects in Smith-Lemli-Opitz syndrome
Defective 3β-hydroxysterol-Δ 7 -reductase (DHCR7) in the developmental disorder, Smith-Lemli-Opitz syndrome (SLOS), results in a deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). Here, we show that loss of DHCR7 causes accumulation of 7-DHC-derived oxysterol metabolites, premature neurogenesis from murine or human cortical neural precursors, and depletion of the cortical precursor pool, both in vitro and in vivo. We found that a major oxysterol, 3β,5α-dihydroxycholest-7-en-6-one (DHCEO), mediates these effects by initiating crosstalk between glucocorticoid receptor (GR) and neurotrophin receptor kinase TrkB. Either loss of DHCR7 or direct exposure to DHCEO causes hyperactivation of GR and TrkB and their downstream MEK-ERK-C/EBP signaling pathway in cortical neural precursors. Moreover, direct inhibition of GR activation with an antagonist or inhibition of DHCEO accumulation with antioxidants rescues the premature neurogenesis phenotype caused by the loss of DHCR7 . These results suggest that GR could be a new therapeutic target against the neurological defects observed in SLOS.
Journal Article
Self-Knowledge, Who God Is, and a Cure for our Deepest Shame: A Few Reflections on Till We Have Faces
is a retelling of the Cupid/Psyche myth with a few twists, namely, a nonstandard narrator and the inability of Psyche’s sister, Orual, to see the palace. Both innovations lead the reader to understand better the dynamics at play in Orual’s effort to disrupt Psyche’s life with her husband/god. The inability to see, on Orual’s part, at first suggests that the nature of the story is primarily epistemological. What is it that can be reasonably known or inferred? Digging deeper, however, reveals that the epistemic elements are actually penultimate, and that instead the book bolsters an ethically robust epistemology. Who we are deeply affects what we can see. Before Orual could apprehend the nature of the gods, she had to be brutally honest about who she herself was. A victim of abuse who was constantly shamed for reasons beyond her control, she is a sympathetic character in several ways, but she gradually moves from being victim to victimizer, treating others as means to ends, and, in the case of Psyche, ‘loving’ her in a way that was more hate than love. Self-knowledge was needed for Orual to apprehend the truth. She comes to realize her treatment of Bardia, Batta, Redival, and especially Psyche was not as pure and altruistic as she had thought. She had to come to terms with the ugliness within herself, and her penchant for consuming others, before she could hope to see the beauty and love of the gods for what they were.
Journal Article
C. S. Lewis’s Christian Apologetics
In C. S. Lewis's Christian Apologetics: Pro and Con, ten articulate defenders and critics of Lewis's apologetics square off and debate the merits of Lewis's central arguments for Christian belief.
eBook
Tryptanthrin Analogs Substoichiometrically Inhibit Seeded and Unseeded Tau4RD Aggregation
Microtubule-associated protein tau is an intrinsically disordered protein (IDP) that forms characteristic fibrillar aggregates in several diseases, the most well-known of which is Alzheimer's disease (AD). Despite keen interest in disrupting or inhibiting tau aggregation to treat AD and related dementias, there are currently no FDA-approved tau-targeting drugs. This is due, in part, to the fact that tau and other IDPs do not exhibit a single well-defined conformation but instead populate a fluctuating conformational ensemble that precludes finding a stable \"druggable\" pocket. Despite this challenge, we previously reported the discovery of two novel families of tau ligands, including a class of aggregation inhibitors, identified through a protocol that combines molecular dynamics, structural analysis, and machine learning. Here we extend our exploration of tau druggability with the identification of tryptanthrin and its analogs as potent, substoichiometric aggregation inhibitors, with the best compounds showing potencies in the low nanomolar range even at a ~100-fold molar excess of tau4RD. Moreover, conservative changes in small molecule structure can have large impacts on inhibitory potency, demonstrating that similar structure-activity relationship (SAR) principles as used for traditional drug development also apply to tau and potentially to other IDPs.Competing Interest StatementA.N. received in-kind support for research from Takeda Pharmaceutical Co. through the Seattle Partnership for Research on Innovative Therapies. E.C., J.S., T.N. and K.C. are employees of Takeda Pharmaceutical Co.
Paper
C.S. Lewis's Christian Apologetics: Pro and Con
Are C. S. Lewis's major arguments in defense of Christian belief sound? In C. S. Lewis's Christian Apologetics: Pro and Con, defenders and critics of Lewis's apologetics square off and debate the merits of Lewis's arguments from desire, from reason, from morality, the \"trilemma\" argument for the divinity of Christ, as well as Lewis's response to the problem of evil. By means of these lively, in-depth debates, readers will emerge with a deeper understanding and appreciation of today's most influential Christian apologist.
eBook