Transglutaminases (denoted TG or TGM) are externalized from cells via an unknown unconventional secretory pathway. Here, we show for the first time that purinergic signaling regulates active secretion of TG2 (also known as TGM2), an enzyme with a pivotal role in stabilizing extracellular matrices and modulating cell–matrix interactions in tissue repair. Extracellular ATP promotes TG2 secretion by macrophages, and this can be blocked by a selective antagonist against the purinergic receptor P2X7 (P2X7R, also known as P2RX7). Introduction of functional P2X7R into HEK293 cells is sufficient to confer rapid, regulated TG2 export. By employing pharmacological agents, TG2 release could be separated from P2X7R-mediated microvesicle shedding. Neither Ca2+ signaling alone nor membrane depolarization triggered TG2 secretion, which occurred only upon receptor membrane pore formation and without pannexin channel involvement. A gain-of-function mutation in P2X7R associated with autoimmune disease caused enhanced TG2 externalization from cells, and this correlated with increased pore activity. These results provide a mechanistic explanation for a link between active TG2 secretion and inflammatory responses, and aberrant enhanced TG2 activity in certain autoimmune conditions.

eveningâ€"was not consistent with the diagnostic classifications with which these patterns have been classically associated. Furthermore, analyses of the diurnal patterns of eleven specific depressive symp tonis revealed that each symptom showed some diurnal pattern, with dysphoric mood, somatic complaints, and anxiety showing, on the average, the greatest susceptibility to diurnal pattern.

BackgroundStratifying patient populations by risk of adverse events was believed to support preventive care for those identified, but recent evidence does not support this. Emergency admission risk stratification (EARS) tools have been widely promoted in UK policy and GP contracts.AimTo describe availability and use of EARS tools across the UK, and identify factors perceived to influence implementation.Design and settingCross-sectional survey in UK.MethodOnline survey of 235 organisations responsible for UK primary care: 209 clinical commissioning groups (CCGs) in England; 14 health boards in Scotland; seven health boards in Wales; and five local commissioning groups (LCGs) in Northern Ireland. Analysis results are presented using descriptive statistics for closed questions and by theme for open questions.ResultsResponses were analysed from 171 (72.8%) organisations, of which 148 (86.5%) reported that risk tools were available in their areas. Organisations identified 39 different EARS tools in use. Promotion by NHS commissioners, involvement of clinical leaders, and engagement of practice managers were identified as the most important factors in encouraging use of tools by general practices. High staff workloads and information governance were identified as important barriers. Tools were most frequently used to identify individual patients, but also for service planning. Nearly 40% of areas using EARS tools reported introducing or realigning services as a result, but relatively few reported use for service evaluation.ConclusionEARS tools are widely available across the UK, although there is variation by region. There remains a need to align policy and practice with research evidence.

In this paper we develop the theory of presentations for globular operads and construct presentations for the globular operads corresponding to several key theories of n-category for n ⩽ 4. Contents 1. Introduction 1 1.1. Organisation of this paper 2 Acknowledgements 2 2. The free strict higher category monads 2 3. Globular operads 7 4. Algebras for globular operads 10 5. Contractibility 13 6. Presentations for globular operads 18 7. The globular operads for weak unbiased higher categories 28 8. Globular operads for higher categories 32 9. Examples of n-globular operads for n-categories 36 9.1. Weak n-categories 37 9.2. n-categories with weak units 42 9.3. n-categories with weak interchange laws 46 Appendix A. The free-forgetful presentation adjunction 49 References 511 By an algebraic notion of higher category we mean a notion of higher category for which composition and its associated coherence are given by specified operations satisfying equational axioms.

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