A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules.

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states

GRB 180620A: Evidence for Late-time Energy Injection

The early optical emission of gamma-ray bursts (GRBs) gives an opportunity to understand the central engine and first stages of these events. About 30% of GRBs present flares whose origin is still a subject of discussion. We present optical photometry of GRB 180620A with the COATLI telescope and RATIR instrument. COATLI started to observe from the end of prompt emission at T + 39.3 s and RATIR from T + 121.4 s. We supplement the optical data with the X-ray light curve from Swift/XRT. We observe an optical flare from T + 110 s to T + 550 s, with a temporal index decay α O,decay = 1.32 ± 0.01, and Δt/t = 1.63, which we interpret as the signature of a reverse shock component. After the initial normal decay the light curves show a long plateau from T + 500 s to T + 7800 s in both X-rays and the optical before decaying again after an achromatic jet break at T + 7800 s. Fluctuations are seen during the plateau phase in the optical. Adding to the complexity of GRB afterglows, the plateau phase (typically associated with the coasting phase of the jet) is seen in this object after the "normal" decay phase (associated with the deceleration phase of the jet), and the jet break phase occurs directly after the plateau. We suggest that this sequence of events can be explained by a rapid deceleration of the jet with t d ≲ 40 s due to the high density of the environment (≈100 cm-3) followed by reactivation of the central engine, which causes the flare and powers the plateau phase

The sub-energetic GRB 031203 as a cosmic analogue to GRB 980425

Over the six years since the discovery of the gamma-ray burst GRB 980425, associated with the nearby (distance, ~40 Mpc) supernova 1998bw, astronomers have fiercely debated the nature of this event. Relative to bursts located at cosmological distances, (redshift, z~1), GRB 980425 was under-luminous in gamma-rays by three orders of magnitude. Radio calorimetry showed the explosion was sub-energetic by a factor of 10. Here, we report observations of the radio and X-ray afterglow of the recent z=0.105 GRB 031203 and demonstrate that it too is sub-energetic. Our result, when taken together with the low gamma-ray luminosity, suggest that GRB 031203 is the first cosmic analogue to GRB 980425. We find no evidence that this event was a highly collimated explosion viewed off-axis. Like GRB 980425, GRB 031203 appears to be an intrinsically sub-energetic gamma-ray burst. Such sub-energetic events have faint afterglows. Intensive follow-up of faint bursts with smooth gamma-ray light curves (common to both GRBs 031203 and 980425) may enable us to reveal their expected large population.Comment: To Appear in Nature, August 5, 200

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Motivated proteins: a web application for studying small three-dimensional protein motifs

<b>BACKGROUND:</b> Small loop-shaped motifs are common constituents of the three-dimensional structure of proteins. Typically they comprise between three and seven amino acid residues, and are defined by a combination of dihedral angles and hydrogen bonding partners. The most abundant of these are alphabeta-motifs, asx-motifs, asx-turns, beta-bulges, beta-bulge loops, beta-turns, nests, niches, Schellmann loops, ST-motifs, ST-staples and ST-turns.We have constructed a database of such motifs from a range of high-quality protein structures and built a web application as a visual interface to this. <b>DESCRIPTION:</b> The web application, Motivated Proteins, provides access to these 12 motifs (with 48 sub-categories) in a database of over 400 representative proteins. Queries can be made for specific categories or sub-categories of motif, motifs in the vicinity of ligands, motifs which include part of an enzyme active site, overlapping motifs, or motifs which include a particular amino acid sequence. Individual proteins can be specified, or, where appropriate, motifs for all proteins listed. The results of queries are presented in textual form as an (X)HTML table, and may be saved as parsable plain text or XML. Motifs can be viewed and manipulated either individually or in the context of the protein in the Jmol applet structural viewer. Cartoons of the motifs imposed on a linear representation of protein secondary structure are also provided. Summary information for the motifs is available, as are histograms of amino acid distribution, and graphs of dihedral angles at individual positions in the motifs. <b>CONCLUSION:</b> Motivated Proteins is a publicly and freely accessible web application that enables protein scientists to study small three-dimensional motifs without requiring knowledge of either Structured Query Language or the underlying database schem

Determinants of adults' intention to vaccinate against pandemic swine flu

This article has been made available through the Brunel Open Access Publishing Fund.This article has been made available through the Brunel Open Access Publishing Fund.Background: Vaccination is one of the cornerstones of controlling an influenza pandemic. To optimise vaccination rates in the general population, ways of identifying determinants that influence decisions to have or not to have a vaccination need to be understood. Therefore, this study aimed to predict intention to have a swine influenza vaccination in an adult population in the UK. An extension of the Theory of Planned Behaviour provided the theoretical framework for the study. Methods: Three hundred and sixty two adults from the UK, who were not in vaccination priority groups, completed either an online (n = 306) or pen and paper (n = 56) questionnaire. Data were collected from 30th October 2009, just after swine flu vaccination became available in the UK, and concluded on 31st December 2009. The main outcome of interest was future swine flu vaccination intentions. Results: The extended Theory of Planned Behaviour predicted 60% of adults’ intention to have a swine flu vaccination with attitude, subjective norm, perceived control, anticipating feelings of regret (the impact of missing a vaccination opportunity), intention to have a seasonal vaccine this year, one perceived barrier: “I cannot be bothered to get a swine flu vaccination” and two perceived benefits: “vaccination decreases my chance of getting swine flu or its complications” and “if I get vaccinated for swine flu, I will decrease the frequency of having to consult my doctor,” being significant predictors of intention. Black British were less likely to intend to have a vaccination compared to Asian or White respondents. Conclusions: Theoretical frameworks which identify determinants that influence decisions to have a pandemic influenza vaccination are useful. The implications of this research are discussed with a view to maximising any future pandemic influenza vaccination uptake using theoretically-driven applications.This article is available through the Brunel Open Access Publishing Fund