The biofilm matrix scaffold of Pseudomonas aeruginosa contains G-quadruplex extracellular DNA structures.

Extracellular DNA, or eDNA, is recognised as a critical biofilm component; however, it is not understood how it forms networked matrix structures. Here, we isolate eDNA from static-culture Pseudomonas aeruginosa biofilms using ionic liquids to preserve its biophysical signatures of fluid viscoelasticity and the temperature dependency of DNA transitions. We describe a loss of eDNA network structure as resulting from a change in nucleic acid conformation, and propose that its ability to form viscoelastic structures is key to its role in building biofilm matrices. Solid-state analysis of isolated eDNA, as a proxy for eDNA structure in biofilms, reveals non-canonical Hoogsteen base pairs, triads or tetrads involving thymine or uracil, and guanine, suggesting that the eDNA forms G-quadruplex structures. These are less abundant in chromosomal DNA and disappear when eDNA undergoes conformation transition. We verify the occurrence of G-quadruplex structures in the extracellular matrix of intact static and flow-cell biofilms of P. aeruginosa, as displayed by the matrix to G-quadruplex-specific antibody binding, and validate the loss of G-quadruplex structures in vivo to occur coincident with the disappearance of eDNA fibres. Given their stability, understanding how extracellular G-quadruplex structures form will elucidate how P. aeruginosa eDNA builds viscoelastic networks, which are a foundational biofilm property

Endometrial stromal cells of women with recurrent miscarriage fail to discriminate between high- and low-quality human embryos

Background The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. Methodology/Principal Findings Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001). Conclusions H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM

Explaining counterterrorism in the UK: Normal politics, securitized politics or performativity of the neoliberal state?

This paper seeks to explore the politics of counter terrorism in the UK. It argues that for a number of reasons, counter terrorism policy has been separated off from other policy areas and seen as securitised, exceptional or just different. The paper argues that such a separation from “normal” politics is problematic, both conceptually and empirically. It argues that much can be gained by considering counter terrorism policy through the lenses, concepts and debates which feature in other areas of British politics. The paper then examines two such lenses/debates – depoliticisation and neoliberalism. An argument is developed that counter terrorism policy is not, in the main, depoliticised, but rather overt, politicised and visible. This prominence, it is argued, is due to the ways in which neoliberalism has reduced many of the traditional roles of the state. Drawing on the work of Wacquant and Hall, the paper argues that in the absence of such traditional roles, counter terrorism offers the state an opportunity to perform its own “stateness”, to visibly display its sovereign power in a context of ever more (self-imposed) diminished powers

Medication administration errors for older people in long-term residential care

Background Older people in long-term residential care are at increased risk of medication errors. The purpose of this study was to evaluate a computerised barcode medication management system designed to improve drug administrations in residential and nursing homes, including comparison of error rates and staff awareness in both settings. Methods All medication administrations were recorded prospectively for 345 older residents in thirteen care homes during a 3-month period using the computerised system. Staff were surveyed to identify their awareness of administration errors prior to system introduction. Overall, 188,249 attempts to administer medication were analysed to determine the prevalence of potential medication administration errors (MAEs). Error classifications included attempts to administer medication at the wrong time, to the wrong person or discontinued medication. Analysis compared data at residential and nursing home level and care and nursing staff groups. Results Typically each resident was exposed to 206 medication administration episodes every month and received nine different drugs. Administration episodes were more numerous (p < 0.01) in nursing homes (226.7 per resident) than in residential homes (198.7). Prior to technology introduction, only 12% of staff administering drugs reported they were aware of administration errors being averted in their care home. Following technology introduction, 2,289 potential MAEs were recorded over three months. The most common MAE was attempting to give medication at the wrong time. On average each resident was exposed to 6.6 potential errors. In total, 90% of residents were exposed to at least one MAE with over half (52%) exposed to serious errors such as attempts to give medication to the wrong resident. MAEs rates were significantly lower (p < 0.01) in residential homes than nursing homes. The level of non-compliance with system alerts was low in both settings (0.075% of administrations) demonstrating virtually complete error avoidance. Conclusion Potentially inappropriate administration of medication is a serious problem in long-term residential care. A computerised barcode system can accurately and automatically detect inappropriate attempts to administer drugs to residents. This tool can reliably be used by care staff as well as nurses to improve quality of care and patient safety

Assessment of the centre of pressure pattern and moments about S2 in scoliotic subjects during normal walking

Background Context: Research employing gait measurements indicate asymmetries in ground reaction forces and suggest relationships between these asymmetries, neurological dysfunction and spinal deformity. Although, studies have documented the use of centre of pressure (CoP) and net joint moments in gait assessment and have assessed centre of mass (CoM)-CoP distance relationships in clinical conditions, there is a paucity of information relating to the moments about CoM. It is commonly considered that CoM is situated around S2 vertebra in normal upright posture and hence this study uses S2 vertebral prominence as reference point relative to CoM. Purpose: To assess and establish asymmetry in the CoP pattern and moments about S2 vertebral prominence during level walking and its relationship to spinal deformity in adolescents with scoliosis. Patient sample: Nine Adolescent Idiopathic Scoliosis subjects (8 females and 1 male with varying curve magnitudes and laterality) scheduled for surgery within 2-3 days after data collection, took part in this study. Outcome measures: Kinetic and Kinematic Gait assessment was performed with an aim to estimate the CoP displacement and the moments generated by the ground reaction force about the S2 vertebral prominence during left and right stance during normal walking. Methods: The study employed a strain gauge force platform to estimate the medio-lateral and anterior-posterior displacement of COP and a six camera motion analysis system to track the reflective markers to assess the kinematics. The data were recorded simultaneously. Results: Results indicate wide variations in the medio lateral direction CoP, which could be related to the laterality of both the main and compensation curves. This variation is not evident in the anterior-posterior direction. Similar results were recorded for moments about S2 vertebral prominence. Subjects with higher left compensation curve had greater displacement to the left. Conclusion: Although further longitudinal studies are needed, results indicate that the variables identified in this study are applicable to initial screening and surgical evaluation of scoliosis. © 2008 Chockalingam et al; licensee BioMed Central Ltd

The Second Transmembrane Domain of P2X7 Contributes to Dilated Pore Formation

Activation of the purinergic receptor P2X7 leads to the cellular permeability of low molecular weight cations. To determine which domains of P2X7 are necessary for this permeability, we exchanged either the C-terminus or portions of the second transmembrane domain (TM2) with those in P2X1 or P2X4. Replacement of the C-terminus of P2X7 with either P2X1 or P2X4 prevented surface expression of the chimeric receptor. Similarly, chimeric P2X7 containing TM2 from P2X1 or P2X4 had reduced surface expression and no permeability to cationic dyes. Exchanging the N-terminal 10 residues or C-terminal 14 residues of the P2X7 TM2 with the corresponding region of P2X1 TM2 partially restored surface expression and limited pore permeability. To further probe TM2 structure, we replaced single residues in P2X7 TM2 with those in P2X1 or P2X4. We identified multiple substitutions that drastically changed pore permeability without altering surface expression. Three substitutions (Q332P, Y336T, and Y343L) individually reduced pore formation as indicated by decreased dye uptake and also reduced membrane blebbing in response to ATP exposure. Three others substitutions, V335T, S342G, and S342A each enhanced dye uptake, membrane blebbing and cell death. Our results demonstrate a critical role for the TM2 domain of P2X7 in receptor function, and provide a structural basis for differences between purinergic receptors. © 2013 Sun et al

A conceptual approach to enhance the well-being of elderly people

The number of elderly people living alone is increasing. Consequently, a lot of research works have been addressing this issue in order to propose solutions that can enhance the quality of life of elderly people. Most of them have been concerned in dealing with objective issues such as forgetfulness or detecting falls. In this paper, we propose a conceptual approach of a system that intends to enhance the daily sense of user’s well-being. For that, our proposal consists in a system that works as a social network and a smartwatch application that works unobtrusively and collects the user’s physiological data. In addition, we debate how important features such as to detect user’s affective states and to potentiate user’s memory could be implemented. Our study shows that there are still some important limitations which affect the success of applications built in the context of elderly care and which are mostly related with accuracy and usability of this kind of system. However, we believe that with our approach we will be able to address some of those limitations and define a system that can enhance the well-being of elderly people and improve their cognitive capabilities.The work presented in this paper has been developed under the EUREKA - ITEA3 Project PHE (PHE-16040), and by National Funds through FCT (Fundação para a Ciência e a Tecnologia) under the projects UID/EEA/00760/2019 and UID/CEC/00319/2019 and by NORTE-01-0247-FEDER-033275 (AIRDOC - “Aplicação móvel Inteligente para suporte individualizado e monitorização da função e sons Respiratórios de Doentes Obstrutivos Crónicos ”) by NORTE 2020 (Programa Operacional Regional do Norte)

Biomechanical spinal growth modulation and progressive adolescent scoliosis – a test of the 'vicious cycle' pathogenetic hypothesis: Summary of an electronic focus group debate of the IBSE

There is no generally accepted scientific theory for the causes of adolescent idiopathic scoliosis (AIS). As part of its mission to widen understanding of scoliosis etiology, the International Federated Body on Scoliosis Etiology (IBSE) introduced the electronic focus group (EFG) as a means of increasing debate on knowledge of important topics. This has been designated as an on-line Delphi discussion. The text for this debate was written by Dr Ian A Stokes. It evaluates the hypothesis that in progressive scoliosis vertebral body wedging during adolescent growth results from asymmetric muscular loading in a "vicious cycle" (vicious cycle hypothesis of pathogenesis) by affecting vertebral body growth plates (endplate physes). A frontal plane mathematical simulation tested whether the calculated loading asymmetry created by muscles in a scoliotic spine could explain the observed rate of scoliosis increase by measuring the vertebral growth modulation by altered compression. The model deals only with vertebral (not disc) wedging. It assumes that a pre-existing scoliosis curve initiates the mechanically-modulated alteration of vertebral body growth that in turn causes worsening of the scoliosis, while everything else is anatomically and physiologically 'normal' The results provide quantitative data consistent with the vicious cycle hypothesis. Dr Stokes' biomechanical research engenders controversy. A new speculative concept is proposed of vertebral symphyseal dysplasia with implications for Dr Stokes' research and the etiology of AIS. What is not controversial is the need to test this hypothesis using additional factors in his current model and in three-dimensional quantitative models that incorporate intervertebral discs and simulate thoracic as well as lumbar scoliosis. The growth modulation process in the vertebral body can be viewed as one type of the biologic phenomenon of mechanotransduction. In certain connective tissues this involves the effects of mechanical strain on chondrocytic metabolism a possible target for novel therapeutic intervention

Binary and Millisecond Pulsars at the New Millennium

We review the properties and applications of binary and millisecond pulsars. Our knowledge of these exciting objects has greatly increased in recent years, mainly due to successful surveys which have brought the known pulsar population to over 1300. There are now 56 binary and millisecond pulsars in the Galactic disk and a further 47 in globular clusters. This review is concerned primarily with the results and spin-offs from these surveys which are of particular interest to the relativity community.Comment: 59 pages, 26 figures, 5 tables. Accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org