Let's cross-link: diverse functions of the promiscuous cellular transglutaminase factor XIII-A

Factor XIII is a tranglutaminase enzyme that catalyzes the formation of ε‐(γ‐glutamyl)lysyl isopeptide bonds in protein substrates. The plasma form, FXIII‐A2B2, has an established function in hemostasis, where its primary substrate is fibrin. A deficiency in FXIII manifests as a severe bleeding diathesis, underscoring its importance in this pathway. The cellular form of the enzyme, a homodimer of the A‐subunits, denoted FXIII‐A, has not been studied in as extensive detail. FXIII‐A was generally perceived to remain intracellular, owing to the lack of a classical signal peptide for its release. In the last decade, emerging evidence has revealed that this diverse transglutaminase can be externalized from cells, by an as yet unknown mechanism, and can cross‐link extracellular substrates and participate in a number of diverse pathways. The FXIII‐A gene (F13A1) is expressed in cells of bone marrow and mesenchymal lineage, notably megakaryocytes, monocytes/macrophages, dendritic cells, chrondrocytes, osteoblasts, and preadipocytes. The biological processes that FXIII‐A is coupled with, such as wound healing, phagocytosis, and bone and matrix remodeling, reflect its expression in these cell types. This review describes the mounting evidence that this cellular transglutaminase can be externalized, usually in response to stimuli, and participate in extracellular cross‐linking reactions. A corollary of being involved in these biological pathways is the participation of FXIII‐A in pathological processes. In conclusion, the functions of this transglutaminase extend far beyond its role in hemostasis, and our understanding of this enzyme in terms of its secretion, regulation and substrates is in its infancy

Diagnostic accuracy of a brief screening tool forAttention Deficit/Hyperactivity Disorder in UK prison inmates

BackgroundAttention deficit hyperactivity disorder (ADHD) is overrepresented in prison, making it imperative to identify a screening tool that can be quickly applied to efficiently detect the disorder. We explored the discrimination ability of a widely used ADHD screen, the Barkley Adult ADHD Rating Scale (BAARS-IV), against a clinical diagnostic interview. A brief version of the screen was then developed in order to simplify its use in the prison context, and maximize its diagnostic properties.MethodA cross-sectional study of 390 male prison inmates was performed in the UK, all participants were screened and interviewed via the Diagnostic Interview for ADHD in Adults 2.0 (DIVA-2).ResultsA total of 47 (12.1%) inmates screened positive for ADHD using the full BAARS-IV, and 96 (24.6%) were clinically diagnosed, for a sensitivity of 37.9 and a specificity of 96.3. Our models identified the six items that most predicted ADHD diagnosis, with adjusted odds ratios ranging from 2.66 to 4.58. Sensitivity, specificity and accuracy were 0.82, 0.84 and 0.84, respectively, for the developed brief scale, and 0.71, 0.85 and 0.81 for its validation. Weighted probability scores produced an area under the curve of 0.89 for development, and 0.82 for validation of the brief scale.ConclusionsThe original BAARS-IV performed poorly at identifying prison inmates with ADHD. Our developed brief scale substantially improved diagnostic accuracy. The brief screening instrument has great potential to be used as an accurate and resource-effective tool to screen young people and adults for likely ADHD in the criminal justice system.</jats:sec

The limits of process: On (re)reading Henri Bergson

This article offers a reading of the work of Henri Bergson as it pertains to organizations through the lens of ideas drawn from critical realism. It suggests an alternative to interpretations based on a stark division between process and realist perspectives. Much of the existing literature presents a rather partial view of Bergson’s work. A review suggests some interesting parallels with themes in critical realism, notably the emergence of mind. Critical realism has a focus on process at its heart, but is also concerned with how the products of such processes become stabilized and form the conditions for action. This suggests that attention might usefully be paid to the relationship between organizational action and the sedimented practices grouped under the heading of ‘routines’. More attention to Bergson’s account of the relationship between instinct, intuition and intelligence provides a link to the social character of thought, something which can be mapped on to Archer’s work on reflexivity and the ‘internal conversation’. This suggests that our analyses need to pay attention to both memory and history, to building and dwelling, rather than the one-sided focus found in some process theory accounts

Single-chain factor XII exhibits activity when complexed to polyphosphate

© 2014 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.Peer reviewedPublisher PD

Residual Stresses in Glasses

The history dependence of the glasses formed from flow-melted steady states by a sudden cessation of the shear rate $\dot\gamma$ is studied in colloidal suspensions, by molecular dynamics simulations, and mode-coupling theory. In an ideal glass, stresses relax only partially, leaving behind a finite persistent residual stress. For intermediate times, relaxation curves scale as a function of $\dot\gamma t$, even though no flow is present. The macroscopic stress evolution is connected to a length scale of residual liquefaction displayed by microscopic mean-squared displacements. The theory describes this history dependence of glasses sharing the same thermodynamic state variables, but differing static properties.Comment: submitted to Physical Revie

Imaging glutathione depletion in the rat brain using ascorbate-derived hyperpolarized MR and PET probes.

Oxidative stress is a critical feature of several common neurologic disorders. The brain is well adapted to neutralize oxidative injury by maintaining a high steady-state concentration of small-molecule intracellular antioxidants including glutathione in astrocytes and ascorbic acid in neurons. Ascorbate-derived imaging probes for hyperpolarized 13C magnetic resonance spectroscopy and positron emission tomography have been used to study redox changes (antioxidant depletion and reactive oxygen species&nbsp;accumulation) in vivo. In this study, we applied these imaging probes to the normal rat brain and a rat model of glutathione depletion. We first studied hyperpolarized [1-13C]dehydroascorbate in the normal rat brain, demonstrating its robust conversion to [1-13C]vitamin C, consistent with rapid transport of the oxidized form across the blood-brain barrier. We next showed that the kinetic rate of this conversion decreased by nearly 50% after glutathione depletion by diethyl maleate treatment. Finally, we showed that dehydroascorbate labeled for positron emission tomography, namely [1-11C]dehydroascorbate, showed no change in brain signal accumulation after diethyl maleate treatment. These results suggest that hyperpolarized [1-13C]dehydroascorbate may be used to non-invasively detect oxidative stress in common disorders of the brain

Study protocol for screening and diagnosis of fetal alcohol spectrum disorders (FASD) among young people sentenced to detention in Western Australia

Introduction: Prenatal alcohol exposure can cause lifelong disability, including physical, cognitive and behavioural deficits, known as fetal alcohol spectrum disorders (FASD). Among individuals with FASD, engagement with justice services is common. Little is known about the prevalence of FASD among young people engaged with the Australian justice system. This study aims to establish FASD prevalence among sentenced young people in detention in Western Australia (WA), and use the findings to develop a screening tool for use among young people entering detention. Translation of these results will guide the management and support of young people in detention and will have significant implications on the lives of young people with FASD and the future of Australian youth justice services. Methods and analysis: Any sentenced young person in WA aged 10-17...years 11...months is eligible to participate. Young people are assessed for FASD by a multidisciplinary team. Standardised assessment tools refined for the Australian context are used, acknowledging the language and social complexities involved. Australian diagnostic guidelines for FASD will be applied. Information is obtained from young people, responsible adults, teachers and custodial officers. Individualised results and management plans for each young person are communicated to the young person and responsible adult. Prevalence of FASD will be reported and multivariate methods used to identify variables most predictive of FASD and to optimise the predictive value of screening. Ethics and dissemination: Approvals have been granted by the WA Aboriginal Health Ethics Committee, University of WA Human Research Ethics Committee, Department of Corrective Services, and Department for Child Protection and Family Support. Anonymised findings will be disseminated through peer-reviewed manuscripts, presentations and the media. Extensive consultation with stakeholders (including government agencies, detention centre staff, community service providers, the young people and their families or carers) will be ongoing until findings are disseminated and translated

Fibrinogenolysis and fibrinolysis in Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT)

Acknowledgements The authors would like to thank all the patients whose samples were used as part of this study, and all the NHS Scotland staff who collected patient samples and looked after these patients. We thank Aberdeen Royal Infirmary Haematology laboratory for conducting the anti-platelet factor 4 antibody testing and Dr Sue Pavord, Consultant Haematologist at Oxford Teaching Hospitals for help in gathering clinical data on the patients. Funding This research was supported by The University of Aberdeen Development Trust (RG16009). CSW and NJM are supported by the British Heart Foundation (PG/15/82/31721; PG/20/17/35050).Peer reviewedPublisher PD

Where constructionism and critical realism converge: interrogating the domain of epistemological relativism

The paper interrogates the status, nature and significance of epistemological relativism as a key element of constructionism and critical realism. It finds that epistemological relativism is espoused by authorities in critical realism and marginalized or displaced in the field of management and organization studies, resulting in forms of analysis that are empirically, but not fully critically, realist. This evaluation prompts reflection on the question of whether, how and with what implications epistemological relativism might be recast at the heart of critical realist studies of management and organization

Direct amplification of nodD from community DNA reveals the genetic diversity of Rhizobium leguminosarum in soil

Sequences of nodD, a gene found only in rhizobia, were amplified from total community DNA isolated from a pasture soil. The polymerase chain reaction (PCR) primers used, Y5 and Y6, match nodD from Rhizobium leguminosarum biovar trifolii, R. leguminosarum biovar viciae and Sinorhizobium meliloti. The PCR product was cloned and yielded 68 clones that were identified by restriction pattern as derived from biovar trifolii [11 restriction fragment length polymorphism (RFLP) types] and 15 clones identified as viciae (seven RFLP types). These identifications were confirmed by sequencing. There were no clones related to S. meliloti nodD. For comparison, 122 strains were isolated from nodules of white clover (Trifolium repens) growing at the field site, and 134 from nodules on trap plants of T. repens inoculated with the soil. The nodule isolates were of four nodD RFLP types, with 77% being of a single type. All four of these patterns were also found among the clones from soil DNA, and the same type was the most abundant, although it made up only 34% of the trifolii-like clones. We conclude that clover selects specific genotypes from the available soil population, and that R. leguminosarum biovar trifolii was approximately five times more abundant than biovar viciae in this pasture soil, whereas S. meliloti was rare