Fate Of Abstracts Published In The Proceedings Of The First Annual Perinatal Society Of Australia And New Zealand Congress In 1997

Objectives: To examine the fate of research presented at the first annual Perinatal Society of Australia and New Zealand (PSANZ) Congress in 1997, by determining: the rate of publication in peer-reviewed biomedical journals; publication rate by discipline; journals in which work was published; concordance for aims, conclusions, authors and number of study subjects; and time from presentation to publication. Methods: A MEDLINE search was conducted for any publication in a peer-reviewed journal resulting from a publishable abstract from the proceedings of the first annual PSANZ Congress in 1997. Searching was completed 42 months postcongress. The concordance of aims, conclusions, authors and number of subjects between abstract and published paper was determined. Results: There were 172 publishable abstracts in the proceedings of the PSANZ Congress in 1997, and 78 (45%) were published as 83 articles. Basic sciences had the highest publication rate (67%) and midwifery the lowest (20%). Articles were published in 41 journals, with one-third of the articles in three paediatric journals. There was a match with aims in 75%, and with conclusions in 65%. There were 47/77 with the same number of subjects, 20/77 with more and 10/77 with fewer. There were 22 articles with one author added, 12 had more than one author added, 11 had one author removed and five had more than one author removed. Median time-to-publication was 18 months (interquartile range 9-26 months). Conclusions: A publication rate of 45% is comparable to other conferences. Basic science and neonatology had the highest publication rates. There were considerable differences between abstract and published article in terms of aims, conclusions, number of subjects and authors

Three-year-olds’ comprehension of contrastive and descriptive adjectives: Evidence for contrastive inference

Combining information from adjectives with the nouns they modify is essential for comprehension. Previous research suggests that preschoolers do not always integrate adjectives and nouns, and may instead over-rely on noun information when processing referring expressions (Fernald, Thorpe, & Marchman, 2010; Thorpe, Baumgartner, & Fernald, 2006). This disjointed processing has implications for pragmatics, apparently preventing under-fives from making contrastive inferences (Huang & Snedeker, 2013). Using a novel experimental design that allows preschoolers time to demonstrate their abilities in adjective-noun integration and in contrastive inference, two visual world experiments investigate how English-speaking three-year-olds (N = 73, Mage = 44 months) process size adjectives across syntactic (prenominal; postnominal) and pragmatic (descriptive; contrastive) contexts. We show that preschoolers are able to integrate adjectives and nouns to resolve reference accurately by the end of the referring expression, in a variety of pragmatic and syntactic contexts and in the presence of multiple distractors. We reveal for the first time that they can contrastively infer, given a slowed speed of presentation and visually salient size contrasts. Our findings provide evidence for a continuity in the development of pragmatic skills, which do not appear to be linked to children's language proficiency or speed of processing

Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

BACKGROUND: The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. METHODS: Cultured human glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. RESULTS: Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor) by any cell type at any time point. CONCLUSION: These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells

Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation

Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed

Rationally designed immunogens enable immune focusing following SARS-CoV-2 spike imprinting

Eliciting antibodies to surface-exposed viral glycoproteins can generate protective responses that control and prevent future infections. Targeting conserved sites may reduce the likelihood of viral escape and limit the spread of related viruses with pandemic potential. Here we leverage rational immunogen design to focus humoral responses on conserved epitopes. Using glycan engineering and epitope scaffolding in boosting immunogens, we focus murine serum antibody responses to conserved receptor binding motif (RBM) and receptor binding domain (RBD) epitopes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike imprinting. Although all engineered immunogens elicit a robust SARS-CoV-2-neutralizing serum response, RBM-focusing immunogens exhibit increased potency against related sarbecoviruses, SARS-CoV, WIV1-CoV, RaTG13-CoV, and SHC014-CoV; structural characterization of representative antibodies defines a conserved epitope. RBM-focused sera confer protection against SARS-CoV-2 challenge. Thus, RBM focusing is a promising strategy to elicit breadth across emerging sarbecoviruses without compromising SARS-CoV-2 protection. These engineering strategies are adaptable to other viral glycoproteins for targeting conserved epitopes

Shiga Toxin Binding to Glycolipids and Glycans

Background: Immunologically distinct forms of Shiga toxin (Stx1 and Stx2) display different potencies and disease outcomes, likely due to differences in host cell binding. The glycolipid globotriaosylceramide (Gb3) has been reported to be the receptor for both toxins. While there is considerable data to suggest that Gb3 can bind Stx1, binding of Stx2 to Gb3 is variable. Methodology: We used isothermal titration calorimetry (ITC) and enzyme-linked immunosorbent assay (ELISA) to examine binding of Stx1 and Stx2 to various glycans, glycosphingolipids, and glycosphingolipid mixtures in the presence or absence of membrane components, phosphatidylcholine, and cholesterol. We have also assessed the ability of glycolipids mixtures to neutralize Stx-mediated inhibition of protein synthesis in Vero kidney cells. Results: By ITC, Stx1 bound both Pk (the trisaccharide on Gb3) and P (the tetrasaccharide on globotetraosylceramide, Gb4), while Stx2 did not bind to either glycan. Binding to neutral glycolipids individually and in combination was assessed by ELISA. Stx1 bound to glycolipids Gb3 and Gb4, and Gb3 mixed with other neural glycolipids, while Stx2 only bound to Gb3 mixtures. In the presence of phosphatidylcholine and cholesterol, both Stx1 and Stx2 bound well to Gb3 or Gb4 alone or mixed with other neutral glycolipids. Pre-incubation with Gb3 in the presence of phosphatidylcholine and cholesterol neutralized Stx1, but not Stx2 toxicity to Vero cells

Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion

Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0

Programmed Bending Reveals Dynamic Mechanochemical Coupling in Supported Lipid Bilayers

In living cells, mechanochemical coupling represents a dynamic means by which membrane components are spatially organized. An extra-ordinary example of such coupling involves curvature-dependent polar localization of chemically-distinct lipid domains at bacterial poles, which also undergo dramatic reequilibration upon subtle changes in their interfacial environment such as during sporulation. Here, we demonstrate that such interfacially-triggered mechanochemical coupling can be recapitulated in vitro by simultaneous, real-time introduction of mechanically-generated periodic curvatures and attendant strain-induced lateral forces in lipid bilayers supported on elastomeric substrates. In particular, we show that real-time wrinkling of the elastomeric substrate prompts a dynamic domain reorganization within the adhering bilayer, producing large, oriented liquid-ordered domains in regions of low curvature. Our results suggest a mechanism in which interfacial forces generated during surface wrinkling and the topographical deformation of the bilayer combine to facilitate dynamic reequilibration prompting the observed domain reorganization. We anticipate this curvature-generating model system will prove to be a simple and versatile tool for a broad range of studies of curvature-dependent dynamic reorganizations in membranes that are constrained by the interfacial elastic and dynamic frameworks such as the cell wall, glycocalyx, and cytoskeleton