Changes in IgA-targeted microbiota following fecal transplantation for recurrent Clostridioides difficile infection

Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune–bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor

NIST interlaboratory study on glycosylation analysis of monoclonal antibodies : comparison of results from diverse analytical methods

Glycosylation is a topic of intense current interest in the development of biopharmaceuticals since it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy‑six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation  analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type.. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods

Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease

Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8+ T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression

Antigemination, assimilation and the determination of identity

Avoidance of adjacent consonants that are 'sufficiently identical' - that is, identical except for possible differences in a small subset of specific features - is argued to result from joint satisfaction of a constraint against geminates (identical adjacent consonants) and other active constraints that independently require assimilation with respect to those features ignored in the determination of identity. The crux of the proposal is the dependence of antigemination on independent assimilation processes, a prediction that is independently verified in case studies from English and Lithuanian. The factorial typology of constraints at the core of the proposal is demonstrated to closely fit a significant range of observed cases. © 2005 Cambridge University Press

Phonemes, segments and features

As the token generative phonologist invited to comment on the article by Hickok (henceforth H.), I feel that it is incumbent upon me to both clarify some terms and to counter an assumption about the content of generative theories of phonology made in H.'s article. While I restrict myself most specifically to H.'s article, I hope that these comments are also of some use to others who, like H., aim to integrate the ideas of various traditions in models of speech processing. © 2013 © 2013 Taylor & Francis

Antigemination, assimilation and the determination of identity

Avoidance of adjacent consonants that are 'sufficiently identical' - that is, identical except for possible differences in a small subset of specific features - is argued to result from joint satisfaction of a constraint against geminates (identical adjacent consonants) and other active constraints that independently require assimilation with respect to those features ignored in the determination of identity. The crux of the proposal is the dependence of antigemination on independent assimilation processes, a prediction that is independently verified in case studies from English and Lithuanian. The factorial typology of constraints at the core of the proposal is demonstrated to closely fit a significant range of observed cases. © 2005 Cambridge University Press

Rule interaction conversion operations

Different types of interactions between pairs of phonological rules can be converted into one another using three formal operations that we discuss in this article. One of these conversion operations, rule re-ordering (here called swapping), is well-known; another, flipping, is a more recent finding (Hein et al., 2014). We introduce a third conversion operation that we call cropping. Formal relationships among the members of the set of rule interactions, ex panded by cropping beyond the classical four (feeding, bleeding, counterfeeding, and coun terbleeding) to include four more (mutual bleeding, seeding, counterseeding, and merger), are identified and clarified. We show that these conversion operations exhaustively delimit the set of possible pairwise rule interactions predicted by conjunctive rule ordering (Chomsky & Halle, 1968), and that each interaction is related to each of the others by the application of at most two conversion operations