Update on celiac disease – etiology, differential diagnosis, drug targets, and management advances

Celiac disease (CD) is an immune-mediated enteropathy triggered by exposure to wheat gluten and similar proteins found in rye and barley that affects genetically susceptible persons. This immune-mediated enteropathy is characterized by villous atrophy, intraepithelial lymphocytosis, and crypt hyperplasia. Once thought a disease that largely presented with malnourished children, the wide spectrum of disease activity is now better recognized and this has resulted in a shift in the presenting symptoms of most patients with CD. New advances in testing, both serologic and endoscopic, have dramatically increased the detection and diagnosis of CD. While the gluten-free diet is still the only treatment for CD, recent investigations have explored alternative approaches, including the use of altered nonimmunogenic wheat variants, enzymatic degradation of gluten, tissue transglutaminase inhibitors, induction of tolerance, and peptides to restore integrity to intestinal tight junctions

Generic Enrichment, Reader Expectation, and Metapoetic Trees in Horace's Odes

Generic enrichment, sometimes known as Kreuzung der Gattungen, is a well-known feature of Roman poetry that plays an integral role in Horatian lyric. This study explores Horace’s use of metapoetic trees as a tool for enacting and representing his attempts at generic enrichment in the Odes. After reviewing the traditional origins of genre theory in classical literature and attributing generic enrichment to an Alexandrian and Roman desire to enhance the value of their poetry, this study reconciles the apparent conflict between generic enrichment and prescriptive, invariable literary kinds by recasting genre as a set of expectations shared between author and audience in a continual and ever-evolving literary dialogue. Having done so, this study then reviews the ancient poets’ use of programmatic trees before specifically discussing their potential use by Horace as a means of engaging with the generic expectations of his audience. As proof, this study continues by recasting Odes 2.13, Horace’s poem celebrating his near-death escape from a falling tree, as a generic manifesto which reflects Horace’s successful integration of epic, elegy, and tragedy into the entirety of the Odes. After revealing the multi-generic nature of Odes 2.13, this study concludes by showing how Horace employs metapoetic trees throughout the remainder of the Odes, and particularly within the three poems which revisit the falling tree episode, to transform the divinities to whom Horace attributes his salvation (Faunus, the Muses, and Liber) into symbols of the very genres he has adapted to his lyric verse. In doing so, Horace establishes an interconnected web of arboricentric poems spanning the Odes which comments on the generically enriched nature of Horatian lyric

Affective Experience, Desire, and Reasons for Action

What is the role of affective experience in explaining how our desires provide us with reasons for action? When we desire that p, we are thereby disposed to feel attracted to the prospect that p, or to feel averse to the prospect that not-p. In this paper, we argue that affective experiences – including feelings of attraction and aversion – provide us with reasons for action in virtue of their phenomenal character. Moreover, we argue that desires provide us with reasons for action only insofar as they are dispositions to have affective experiences. On this account, affective experience has a central role to play in explaining how desires provide reasons for action

Laser Microdissection of Narrow Sheath Mutant Maize Uncovers Novel Gene Expression in the Shoot Apical Meristem

Microarrays enable comparative analyses of gene expression on a genomic scale, however these experiments frequently identify an abundance of differentially expressed genes such that it may be difficult to identify discrete functional networks that are hidden within large microarray datasets. Microarray analyses in which mutant organisms are compared to nonmutant siblings can be especially problematic when the gene of interest is expressed in relatively few cells. Here, we describe the use of laser microdissection microarray to perform transcriptional profiling of the maize shoot apical meristem (SAM), a ~100-μm pillar of organogenic cells that is required for leaf initiation. Microarray analyses compared differential gene expression within the SAM and incipient leaf primordium of nonmutant and narrow sheath mutant plants, which harbored mutations in the duplicate genes narrow sheath1 (ns1) and narrow sheath2 (ns2). Expressed in eight to ten cells within the SAM, ns1 and ns2 encode paralogous WUSCHEL1-like homeobox (WOX) transcription factors required for recruitment of leaf initials that give rise to a large lateral domain within maize leaves. The data illustrate the utility of laser microdissection-microarray analyses to identify a relatively small number of genes that are differentially expressed within the SAM. Moreover, these analyses reveal potentially conserved WOX gene functions and implicate specific hormonal and signaling pathways during early events in maize leaf development

Correlated polyhedral rotations in the absence of polarons during electrochemical insertion of lithium in ReO3

Understanding the structural transformations that materials undergo during (de)insertion of Li ions is crucial for designing high-performance intercalation hosts as these deformations can lead to significant capacity fade. Herein, we present a study of the metallic defect perovskite ReO3 to determine whether these distortions are driven by polaronic charge transport (i.e., the electrons and ions moving through the lattice in a coupled way) due to the semiconducting nature of most oxide hosts. Employing numerous techniques, including electrochemical probes, operando X-ray diffraction, X-ray photoelectron spectroscopy, and density functional theory calculations, we find that the cubic structure of ReO3 experiences multiple phase changes involving the correlated twisting of rigid octahedral subunits upon lithiation. This results in exceptionally poor long-term cyclability due to large strains upon lithiation, even though metallic character is maintained throughout. This suggests that phase transformations during alkali ion intercalation are the result of local strains in the lattice and not exclusively due to polaron migration

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning