There's no place like OM:Vesicular sorting and secretion of the peptidylarginine deiminase of Porphyromonas gingivalis

The oral pathogen Porphyromonas gingivalis is one of the major periodontal agents and it has been recently hailed as a potential cause of the autoimmune disease rheumatoid arthritis. In particular, the peptidylarginine deiminase enzyme of P. gingivalis (PPAD) has been implicated in the citrullination of certain host proteins and the subsequent appearance of antibodies against citrullinated proteins, which might play a role in the etiology of rheumatoid arthritis. The aim of this study was to investigate the extracellular localization of PPAD in a large panel of clinical P. gingivalis isolates. Here we show that all isolates produced PPAD. In most cases PPAD was abundantly present in secreted outer membrane vesicles (OMVs) that are massively produced by P. gingivalis, and to minor extent in a soluble secreted state. Interestingly, a small subset of clinical isolates showed drastically reduced levels of the OMV-bound PPAD and secreted most of this enzyme in the soluble state. The latter phenotype is strictly associated with a lysine residue at position 373 in PPAD, implicating the more common glutamine residue at this position in PPAD association with OMVs. Further, one isolate displayed severely restricted vesiculation. Together, our findings show for the first time that neither the major association of PPAD with vesicles, nor P. gingivalis vesiculation per se, are needed for P. gingivalis interactions with the human host

Tasting as a social practice: a methodological experiment in making taste public

Based on fieldwork in the UK and Portugal, this paper considers the relationships between cultural analyses of taste and the embodied activity of tasting. As part of a wider project on the multiple ontologies of ‘freshness’, the paper conceptualises taste as an emergent effect of tasting practices. Drawing on evidence from a series of ‘tasting events’ (where research participants were recorded shopping, cooking and eating a meal with friends and family), the paper explores the multiple dimensions of taste concluding that even the most personal and sensory aspects of tasting food involve a social dimension which we interpret through the lens of practice theory. The paper identifies three specific dimensions of tasting as a social practice involving food’s material and visceral qualities; the links between embodiment and emotion; and the contextual significance of family and social relations. Our findings contribute to recent debates about ‘making taste public’, even in the apparently private context of household consumption

On the mid range: an exercise in disposing (or minding the gaps)

© 2007 SAGE Publications. Post-print version. 12 month embargo by the publisher. Article will be released November 2008.Many efforts to establish concepts and theories of the middle range have sought to find an appropriate balance between theoretical abstraction and the desire to remain faithful to the empirical complexity of phenomenon. As with other forms of expertise, those analyzing socio-technical life face acute tensions in attempting to reconcile the general and the specific in a manner which is regarded as credible. Through a consideration of the self-referential implications of STS critiques of traditional notions of science as well as attempts to establish rules for the acceptability of coercive force, this article develops a sense of what is at stake in attempts by actors and analysts to grasp the general and the specific together. Instead of seeking to identify a point of resolution for the two, it advocates and exemplifies the need to attend to the dilemmas associated with the movement between the general and the specific. The middle range concept of "disposal strategies" is offered both as an aid to the study of socio-technical life and as an example of attending to the movement between the general and specific.ESRC project RES-223-25-005

Minimal to no transfer of certolizumab pegol into breast milk: Results from CRADLE, a prospective, postmarketing, multicentre, pharmacokinetic study

Background Women with chronic inflammatory diseases face uncertainty regarding the safety of biologics during breast feeding. CRADLE was the first industry-sponsored study to evaluate certolizumab pegol (CZP) concentrations in human breast milk and estimate average daily infant dose (ADID) of maternal CZP. Methods CRADLE (NCT02154425) was a pharmacokinetic study of lactating mothers receiving CZP. After ≥3 CZP doses, breast milk samples were collected across one dosing period (14 days for 200 mg every 2 weeks [Q2W]; 28 days for 400 mg every 4 weeks [Q4W]). Optimal analytical methods were developed to determine CZP and polyethylene glycol (PEG) levels in breast milk. ADID and relative infant dose (RID) were estimated. Safety events in mothers and infants were assessed. Results 19 CZP-Treated mothers were screened; 17 entered the sampling period: 16 on 200 mg Q2W, 1 on 400 mg Q4W. 77/137 (56%) breast milk samples had no measurable CZP. For 4/17 mothers, all samples were below the lower limit of quantification (LLOQ). Estimated ADID was 0-0.0104 mg/kg/day; median RID: 0.15%. PEG was undetectable in 134/137 samples (results could not be determined in three samples). Infants of CZP-exposed mothers had a safety profile consistent with that of unexposed similar-Age infants. Conclusion When quantifiable, CZP concentrations were <3× LLOQ (<1% plasma concentration observed with therapeutic dose), indicating no/minimal CZP transfer from plasma to breast milk. RID was 0.15% of maternal dose; <10% is considered unlikely to be of clinical concern. No PEG transfer was observed. CZP absorption by infants via breast milk is unlikely due to its low oral bioavailability and Fc-Â-free molecular structure. These findings are reassuring and support continuation of CZP treatment during breast feeding. Trial registration number NCT02154425; Results