Ascribing Sexual Orientations

The goal of this paper is to suggest a somewhat different approach to the contemporary discussion of human sexual orientations. Instead of examining the nature of sexual orientation itself, it discusses the meanings of ascriptions of sexual orientation. (The discussion is confined to cases where the subject of ascription is female.) The paper begins with a survey of some prevalent ways of interpreting ascriptions of sexual orientation. It then comments on the variations in their meanings, and considers what the speaker is doing when uttering such an ascription. It concludes with some comments about an apparently anomalous sexual orientation, bisexuality

Old age and ageism, impairment and ableism: Exploring the conceptual and material connections

Keywords: old age / aging / ageism / impairment / disability / ableism Among most philosophers and theorists, it is now a truism that identities, or at least some identities, are socially constructed. These identities include gender identity, racial identity, and what we might call ability identity, as a disabled or non-disabled person. To this list I also want to add age identity, in particular, age identity as an elderly or aged person

Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection.

The interplay between a highly polymorphic set of MHC-I alleles and molecular chaperones shapes the repertoire of peptide antigens displayed on the cell surface for T cell surveillance. Here, we demonstrate that the molecular chaperone TAP-binding protein related (TAPBPR) associates with a broad range of partially folded MHC-I species inside the cell. Bimolecular fluorescence complementation and deep mutational scanning reveal that TAPBPR recognition is polarized toward the α2 domain of the peptide-binding groove, and depends on the formation of a conserved MHC-I disulfide epitope in the α2 domain. Conversely, thermodynamic measurements of TAPBPR binding for a representative set of properly conformed, peptide-loaded molecules suggest a narrower MHC-I specificity range. Using solution NMR, we find that the extent of dynamics at "hotspot" surfaces confers TAPBPR recognition of a sparsely populated MHC-I state attained through a global conformational change. Consistently, restriction of MHC-I groove plasticity through the introduction of a disulfide bond between the α1/α2 helices abrogates TAPBPR binding, both in solution and on a cellular membrane, while intracellular binding is tolerant of many destabilizing MHC-I substitutions. Our data support parallel TAPBPR functions of 1) chaperoning unstable MHC-I molecules with broad allele-specificity at early stages of their folding process, and 2) editing the peptide cargo of properly conformed MHC-I molecules en route to the surface, which demonstrates a narrower specificity. Our results suggest that TAPBPR exploits localized structural adaptations, both near and distant to the peptide-binding groove, to selectively recognize discrete conformational states sampled by MHC-I alleles, toward editing the repertoire of displayed antigens

Does Reproductive Justice Demand Insurance Coverage for IVF?

This paper comes out of a panel honoring the work of Anne Donchin (1940-2014), which took place at the 2016 Congress of the International Network on Feminist Approaches to Bioethics (FAB) in Edinburgh. My general aim is to highlight the contributions Anne made to feminist bioethics, and to feminist reproductive ethics in particular. My more specific aim, however, is to have a kind of conversation with Anne, through her work, about whether reproductive justice could demand insurance coverage for in vitro fertilization. I quote liberally from Anne’s work for this purpose, but also to shower the reader with her words, reminding those of us who knew her well what a wonderful colleague she was

Arabidopsis Plasmodesmal Proteome

The multicellular nature of plants requires that cells should communicate in order to coordinate essential functions. This is achieved in part by molecular flux through pores in the cell wall, called plasmodesmata. We describe the proteomic analysis of plasmodesmata purified from the walls of Arabidopsis suspension cells. Isolated plasmodesmata were seen as membrane-rich structures largely devoid of immunoreactive markers for the plasma membrane, endoplasmic reticulum and cytoplasmic components. Using nano-liquid chromatography and an Orbitrap ion-trap tandem mass spectrometer, 1341 proteins were identified. We refer to this list as the plasmodesmata- or PD-proteome. Relative to other cell wall proteomes, the PD-proteome is depleted in wall proteins and enriched for membrane proteins, but still has a significant number (35%) of putative cytoplasmic contaminants, probably reflecting the sensitivity of the proteomic detection system. To validate the PD-proteome we searched for known plasmodesmal proteins and used molecular and cell biological techniques to identify novel putative plasmodesmal proteins from a small subset of candidates. The PD-proteome contained known plasmodesmal proteins and some inferred plasmodesmal proteins, based upon sequence or functional homology with examples identified in different plant systems. Many of these had a membrane association reflecting the membranous nature of isolated structures. Exploiting this connection we analysed a sample of the abundant receptor-like class of membrane proteins and a small random selection of other membrane proteins for their ability to target plasmodesmata as fluorescently-tagged fusion proteins. From 15 candidates we identified three receptor-like kinases, a tetraspanin and a protein of unknown function as novel potential plasmodesmal proteins. Together with published work, these data suggest that the membranous elements in plasmodesmata may be rich in receptor-like functions, and they validate the content of the PD-proteome as a valuable resource for the further uncovering of the structure and function of plasmodesmata as key components in cell-to-cell communication in plants

"The End of Immortality!" Eternal Life and the Makropulos Debate

Responding to a well-known essay by Bernard Williams, philosophers (and a few theologians) have engaged in what I call “the Makropulos debate,” a debate over whether immortality—“living forever”—would be desirable for beings like us. Lacking a firm conceptual grounding in the religious contexts from which terms such as “immortality” and “eternal life” gain much of their sense, the debate has consisted chiefly in a battle of speculative fantasies. Having presented my four main reasons for this assessment, I examine an alternative and neglected conception, the idea of eternal life as a present possession, derived in large part from Johannine Christianity. Without claiming to argue for the truth of this conception, I present its investigation as exemplifying a conceptually fruitful direction of inquiry into immortality or eternal life, one which takes seriously the religious and ethical surroundings of these concepts