bluuebunny/crossref_metadata_2025_split huggingface dataset:
MinC, MinD, and MinE Drive Counter-oscillation of Early-Cell-Division Proteins Prior to Escherichia coli Septum Formation
Authors: Bisicchia Paola , Arumugam Senthil , Schwille Petra , Sherratt David 
Published: December 2013

ABSTRACT
Bacterial cell division initiates with the formation of a ring-like structure at the cell center composed of the tubulin homolog FtsZ (the Z-ring), which acts as a scaffold for the assembly of the cell division complex, the divisome. Previous studies have suggested that the divisome is initially composed of FtsZ polymers stabilized by membrane anchors FtsA and ZipA, which then recruit the remaining division proteins. The MinCDE proteins prevent the formation of the Z-ring at poles by oscillating from pole to pole, thereby ensuring that the concentration of the Z-ring inhibitor, MinC, is lowest at the cell center. We show that prior to septum formation, the early-division proteins ZipA, ZapA, and ZapB, along with FtsZ, assemble into complexes that counter-oscillate with respect to MinC, and with the same period. We propose that FtsZ molecules distal from high concentrations of MinC form relatively slowly diffusing filaments that are bound by ZapAB and targeted to the inner membrane by ZipA or FtsA. These complexes may facilitate the early stages of divisome assembly at midcell. As MinC oscillates toward these complexes, FtsZ oligomerization and bundling are inhibited, leading to shorter or monomeric FtsZ complexes, which become less visible by epifluorescence microscopy because of their rapid diffusion. Reconstitution of FtsZ-Min waves on lipid bilayers shows that FtsZ bundles partition away from high concentrations of MinC and that ZapA appears to protect FtsZ from MinC by inhibiting FtsZ turnover.

IMPORTANCE
A big issue in biology for the past 100 years has been that of how a cell finds its middle. In
Escherichia coli
, over 20 proteins assemble at the cell center at the time of division. We show that the MinCDE proteins, which prevent the formation of septa at the cell pole by inhibiting FtsZ, drive the counter-oscillation of early-cell-division proteins ZapA, ZapB, and ZipA, along with FtsZ. We propose that FtsZ forms filaments at the pole where the MinC concentration is the lowest and acts as a scaffold for binding of ZapA, ZapB, and ZipA: such complexes are disassembled by MinC and reform within the MinC oscillation period before accumulating at the cell center at the time of division. The ability of FtsZ to be targeted to the cell center in the form of oligomers bound by ZipA and ZapAB may facilitate the early stages of divisome assembly.
Dissecting the Machinery That Introduces Disulfide Bonds in Pseudomonas aeruginosa
Authors: Arts Isabelle S. , Ball Geneviève , Leverrier Pauline , Garvis Steven , Nicolaes Valérie , Vertommen Didier , Ize Bérengère , Tamu Dufe Veronica , Messens Joris , Voulhoux Romé , Collet Jean-François 
Published: December 2013

ABSTRACTDisulfide bond formation is required for the folding of many bacterial virulence factors. However, whereas theEscherichia colidisulfide bond-forming system is well characterized, not much is known on the pathways that oxidatively fold proteins in pathogenic bacteria. Here, we report the detailed unraveling of the pathway that introduces disulfide bonds in the periplasm of the human pathogenPseudomonas aeruginosa. The genome ofP. aeruginosauniquely encodes two DsbA proteins (P. aeruginosaDsbA1 [PaDsbA1] and PaDsbA2) and two DsbB proteins (PaDsbB1 and PaDsbB2). We found that PaDsbA1, the primary donor of disulfide bonds to secreted proteins, is maintained oxidizedin vivoby both PaDsbB1 and PaDsbB2.In vitroreconstitution of the pathway confirms that both PaDsbB1 and PaDsbB2 shuttle electrons from PaDsbA1 to membrane-bound quinones. Accordingly, deletion of bothP. aeruginosa dsbB1(PadsbB1) andPadsbB2is required to prevent the folding of severalP. aeruginosavirulence factors and to lead to a significant decrease in pathogenicity. Using a high-throughput proteomic approach, we also analyzed the impact ofPadsbA1deletion on the global periplasmic proteome ofP. aeruginosa, which allowed us to identify more than 20 new potential substrates of this major oxidoreductase. Finally, we report the biochemical and structural characterization of PaDsbA2, a highly oxidizing oxidoreductase, which seems to be expressed under specific conditions. By fully dissecting the machinery that introduces disulfide bonds inP. aeruginosa, our work opens the way to the design of novel antibacterial molecules able to disarm this pathogen by preventing the proper assembly of its arsenal of virulence factors.IMPORTANCEThe human pathogenPseudomonas aeruginosacauses life-threatening infections in immunodepressed and cystic fibrosis patients. The emergence ofP. aeruginosastrains resistant to all of the available antibacterial agents calls for the urgent development of new antibiotics active against this bacterium. The pathogenic power ofP. aeruginosais mediated by an arsenal of extracellular virulence factors, most of which are stabilized by disulfide bonds. Thus, targeting the machinery that introduces disulfide bonds appears to be a promising strategy to combatP. aeruginosa. Here, we unraveled the oxidative protein folding system ofP. aeruginosain full detail. The system uniquely consists of two membrane proteins that generate disulfide bondsde novoto deliver them toP. aeruginosaDsbA1 (PaDsbA1), a soluble oxidoreductase. PaDsbA1 in turn donates disulfide bonds to secreted proteins, including virulence factors. Disruption of the disulfide bond formation machinery dramatically decreasesP. aeruginosavirulence, confirming that disulfide formation systems are valid targets for the design of antimicrobial drugs.
Head injuries among FIS World Cup alpine and freestyle skiers and snowboarders: a 7-year cohort study
Authors: Steenstrup Sophie E , Bere Tone , Bahr Roald 
Published: December 2013

BackgroundTraumatic brain injury is the leading cause of death for skiers and snowboarders. Fatal head injuries have also occurred at the International Ski Federation (FIS) World Cup (WC) level. We therefore wanted to describe the risk of head injuries across disciplines and sex among WC skiers and snowboarders.MethodWe conducted retrospective interviews with FIS WC athletes at the end of seven consecutive seasons (2006–2013) to register injuries sustained during the competitive season. Head injuries were classified as ‘head/face’ injuries and did not include neck or cervical spine injuries. To calculate the exposure, we extracted data from the official FIS website for all WC competitions for each of the athletes interviewed.ResultsA total of 2080 injuries were reported during seven WC seasons. Of these, 245 (11.8%) were head/face injuries. Of the 245 head/face injuries reported, nervous system injuries/concussions were the most common (81.6%) and 58 of these were severe (23.7%). The injury incidence per 1000 competition runs was higher in freestyle (1.8, 95% CI 1.2 to 2.4) than in alpine skiing (0.9, 95% CI 0.6 to 1.2; risk ratio (RR) 2.05, 95% CI 1.25 to 3.46) and snowboard (1.0, 95% CI 0.6 to 1.3; RR 1.85, 95% CI 1.15 to 2.99). Women had a higher injury incidence (5.8, 95% CI 4.8 to 6.9) versus men (3.9, 95% CI 3.2 to 4.6; RR 1.48, 95% CI 1.15 to 1.90) throughout the season (per 100 athletes).ConclusionsThe majority of head/face injuries were nervous system injuries/concussions and one in four injuries was severe. Freestyle skiers had the highest overall head injury incidence. Across all disciplines, the injury incidence was higher in women than in men.
The role of sports physiotherapy at the London 2012 Olympic Games
Authors: Grant Marie-Elaine , Steffen Kathrin , Glasgow Philip , Phillips Nicola , Booth Lynn , Galligan Marie 
Published: December 2013

BackgroundThere is a lack of information on the utilisation of physiotherapy services at the Olympic Games.AimTo better understand the athlete and non-athlete requirements of the physiotherapy services at the Olympic Village Polyclinic during the London 2012 Olympic Games.MethodsFrom 16 July to 14 August 2012, physiotherapy encounters for athletes and non-athletes (National Olympic Committee (NOC) team officials, coaches, team managers, workforce, Olympic family, technical officials and press) were recorded on the ATOS electronic medical records system at the polyclinic in the main Athletes’ Village in Stratford.ResultsOf the 1778 encounters, 1219 (69%) were administered to athletes and 559 (31%) to non-athletes. The anatomical areas most frequently recorded at the first visits for athletes were knee (15.4%), lumbar spine/lower back (15.2%) and upper leg (12.6%) and that for non-athletes were lumbar spine/lower back (19.8%), knee (15.8%) and neck/cervical spine. Muscle (33.3%) and joint injuries (24.8%) were the most common diagnoses in athletes and non-athletes (24.4% and 30.1%). The five most frequently used treatment modalities were therapeutic soft tissue techniques (23.3%), mobilisation techniques (21.8%), taping (8.9%), cryotherapy (6.9%) and exercise prescription (6.4%). The most common cause of athletes’ injuries was overuse (43.6%).ConclusionsThis study of the London 2012 Olympic Games workload highlights the physiotherapy needs of athletes as well as non-athletes and identifies the high numbers of pre-existing and overuse injuries in this setting, providing an insight into the reasons why the athletes seek physiotherapy support during the Olympic Games.
Accountable to whom, for what? An exploration of the early development of Clinical Commissioning Groups in the English NHS
Authors: Checkland Kath , Allen Pauline , Coleman Anna , Segar Julia , McDermott Imelda , Harrison Stephen , Petsoulas Christina , Peckham Stephen 
Published: December 2013

ObjectiveOne of the key goals of the current reforms in the English National Health Service (NHS) under the Health and Social Care Act, 2012, is to increase the accountability of those responsible for commissioning care for patients (clinical commissioning groups (CCGs)), while at the same time allowing them a greater autonomy. This study was set out to explore CCG's developing accountability relationships.DesignWe carried out detailed case studies in eight CCGs, using interviews, observation and documentary analysis to explore their multiple accountabilities.Setting/participantsWe interviewed 91 people, including general practitioners, managers and governing body members in developing CCGs, and undertook 439 h of observation in a wide variety of meetings.ResultsCCGs are subject to a managerial, sanction-backed accountability to NHS England (the highest tier in the new organisational hierarchy), alongside a number of other external accountabilities to the public and to some of the other new organisations created by the reforms. In addition, unlike their predecessor commissioning organisations, they are subject to complex internal accountabilities to their members.ConclusionsThe accountability regime to which CCGs are subject to is considerably more complex than that which applied their predecessor organisations. It remains to be seen whether the twin aspirations of increased autonomy and increased accountability can be realised in practice. However, this early study raises some important issues and concerns, including the risk that the different bodies to whom CCGs are accountable will have differing (or conflicting) agendas, and the lack of clarity over the operation of sanction regimes.
Young people's use of NHS Direct: a national study of symptoms and outcome of calls for children aged 0–15
Authors: Cook E J , Randhawa G , Large S , Guppy A , Chater A M , Pang D 
Published: December 2013

ObjectivesNational Health Service (NHS) Direct provides 24/7 expert telephone-based healthcare information and advice to the public in England. However, limited research has explored the reasons to why calls are made on behalf of young people, as such this study aimed to examine call rate (CR) patterns in younger people to enable a better understanding of the needs of this population in England.SettingNHS Direct, England, UK.Participants and methodsCRs (expressed as calls/100 persons/annum) were calculated for all calls (N=358 503) made to NHS Direct by, or on behalf of, children aged 0–15 during the combined four ‘1-month’ periods within a year (July 2010, October 2010, January 2011 and April 2011). χ² Analysis was used to determine the differences between symptom, outcome and date/time of call.ResultsFor infants aged <1, highest CRs were found for ‘crying’ for male (n=14, 440, CR=13.61) and female (n=13 654, CR=13.46) babies, which is used as a universal assessment applied to all babies. High CRs were also found for symptoms relating to ‘skin/hair/nails’ and ‘colds/flu/sickness’ for all age groups, whereby NHS Direct was able to support patients to self-manage and provide health information for these symptoms for 59.7% and 51.4% of all cases, respectively. Variations in CRs were found for time and age, with highest peaks found for children aged 4–15 in the 15:00–23:00 period and in children aged <1 in the 7:00–15:00 period.ConclusionsThis is the first study to examine the symptoms and outcome of calls made to NHS Direct for and on behalf of young children. The findings revealed how NHS Direct has supported a range of symptoms through the provision of health information and self-care support which provides important information about service planning and support for similar telephone-based services.
Early Experience with a Hepatobiliary and Pancreatic Quality Improvement Program
Authors: O'Reilly Derek , Edmiston Rachel , Bijoor Pooja , Deshpande Rahul , de'Liguori Carino Nicola , Ammori Basil , J. Sherlock David 
Published: December 2013

AbstractThis project aims to assess the impact of the introduction of a hepatobiliary and pancreatic (HPB) Quality Improvement Program (QIP) on postoperative complications following liver, biliary and pancreatic surgery.A prospective analysis of postoperative complications over a six month period was performed. Complications were analysed and graded according to internationally agreed definitions. Justification was sought and errors identified. Weekly meetings were performed to review each complication enabling an action plan to be created to prevent future recurrence. Rates were compared with previously audited and published results, using the chi-square test. A total of 326 procedures were performed over the six months including 30 pancreatectomies, 45 liver resections and 251 other procedures. 37 patients developed complications (11.3%) with 47 complications in total including two deaths. Using the ISGPS grading, eight complications were identified; two grade A, four grade B and two grade C. There were three grade A ISGLS complications and one grade B. 30 complications were justified as unavoidable, 16 as avoidable and one as indeterminate. Action plans included continued monitoring (n=41), formulation of new policy (n=3), individual counselling (n=4), educational offering (n=4). When compared with 2010 complication rates, 114 complications occurred in 233 liver operations during the baseline period, compared with 17 complications in 45 liver operations during the QIP period, OR=0.63 (95% CI: 0.33 to 1.22), p=0.17 and 86 complications occurred in 99 pancreatic resections during the baseline period, compared with 20 complications in 30 pancreatic resections during the QIP period OR=0.30 (95% CI: 0.12 to 0.79), p=0.01The HPB QIP is a rigorous approach to grade every complication and death. A statistically significant reduction in pancreas related complications has already been obtained. Further work is required to determine the persistence and magnitude of this quality improvement.
Implementation of a combined Cardiopulmonary Resuscitation and Treatment Escalation Plan document in a District General Hospital
Authors: Stockdale Claire , Trivedi Bhavi , Jerome Ellen , Salih Samir , Huntley Christopher , Cooke Eleanor , Massey Yolanda , Mella Sophie 
Published: December 2013

AbstractDocumentation of appropriate escalation of treatment was identified as a problem for junior doctors and Critical Care Outreach Nurses at Musgrove Park Hospital. An audit of resuscitation and escalation documentation of all wards found that of the patients who were not for Cardiopulmonary resuscitation (and therefore not for full escalation of care), 78.4% had no documentation of the appropriate level of escalation of treatment should they deteriorate. The majority of junior doctors had experienced cases where they felt that inappropriate treatment had been given, where no escalation plan was documented.Using several Plan, Do, Study, Act (PDSA) cycles, drawing tools used in other trusts and departments, and the views of clinicians, we developed a treatment escalation plan (TEP) tool, to be included in the resuscitation form. This included consideration of referral to critical care, ward based non-invasive ventilation, and appropriate use of intravenous or oral antibiotics. This then prompted the responsible clinician to consider and document appropriate escalation of treatment.The CPR-TEP form was trialed using a quasi-experiment design allowing the aim to be tested using two groups – intervention and control. All patients in the intervention group were not for CPR and therefore had their TEP-CPR form filled in fully (n= 68). The control group consisted of patients who were not for CPR but who did not have a TEP form filled in (n=36).The appropriateness of OOH (out of hours) treatment in those patients who experienced clinical deterioration was judged by questionnaire-based feedback from the in-hours team the following morning. Levels of inappropriate treatment between the two groups were compared to test the aim.At the end of the study period, questionnaire feedback indicated that 11.1% of patients in the group with the new CPR-TEP document had received inappropriate OOH care compared to 44.4% of patients in the group without the document.Using the TEP alongside resuscitation documentation prompts the responsible clinician to consistently consider and document the appropriate escalation of care for their patient, improving communication with the out of hours team and appropriate escalation of care in the event of patient deterioration.
Factors influencing decision-making in relation to timing of gastrostomy insertion in patients with motor neurone disease
Authors: Stavroulakis Theocharis , Baird Wendy O , Baxter Susan K , Walsh Theresa , Shaw Pamela J , McDermott Christopher J 
Published: December 2013

ObjectivesThis study aimed to explore the decision-making process leading up to gastrostomy insertion from the perspective of the patients and their informal carers. Gastrostomy feeding is commonly used to support motor neurone disease patients with dysphagia. However, there is no robust evidence to suggest the optimal timing for gastrostomy insertion.MethodsRetrospective qualitative exploration using semistructured interviews with paired patients and carers in order to elicit their perceptions in relation to gastrostomy timing.Results27 patients consented to the study; of these, 23 underwent a successful gastrostomy. Approximately 3 months following a successful gastrostomy, 10 patients and 8 carers were interviewed. Decision-making in relation to the timing of gastrostomy was described as being a difficult process with individual variations and wishes. A range of factors acted as triggers for taking the decision to proceed with gastrostomy such as prolonged, tiring and effortful meals; the task of food preparation; choking and aspiration; and weight loss. Factors such as the reluctance to give up oral feeding, not realising the potential benefits and negative perceptions of gastrostomy influenced a decision to delay the procedure. A tendency for late insertion was identified despite the opposite advice by health professionals.ConclusionsThe advice for early insertion does not outweigh the personal perceptions and psychosocial factors for patients and their carers. Understanding the factors which influence decision-making on an individual basis is important for information and care provision by healthcare professionals in aiding patients, and their carers, to make informed decisions in relation to gastrostomy timing.
Proper compression landmark and depth for cardiopulmonary resuscitation in patients with pectus excavatum: a study using CT
Authors: Lee Ki Hyun , Kim Kun Woo , Kim Eun Young , Kim Hyung Sik , Kim Jeong Ho , Cho Jinseong , Yang Hyuk Jun 
Published: December 2013

ObjectiveTo determine by chest CT the proper compression landmark and depth for cardiopulmonary resuscitation in patients with pectus excavatum (PE).MethodsThe chest CT of 22 patients with PE (mean age=27 years; range 16–53 years, 10 male) from March 2002 to September 2011 were retrospectively evaluated as follows: length of sternum, external thickness/internal thickness (ET/IT) of the chest and the intrathoracic structures in the level of lower half (LH) of the sternum. In addition, Haller index (HI) and the degree of leftward displacement of the heart were measured. Finally, variables were also measured in an age/sex-matched control group (n=22) with no evidence of any chest wall deformity.ResultsThe sternal length was not different and LH of the sternum was adequate to compress left ventricle (LV) in both groups. Patients had a significant higher HI and showed a greater leftward displacement of LV centre with a mean difference of 11 mm. PE patients showed a lesser ET/IT with a mean difference of approximately 20 mm than controls (mean ET/IT=174±18/70±10 mm vs 199±23/93±15 mm, p<0.001).ConclusionsThe LH of the sternum is an appropriate chest compression landmark in PE patients to compress LV, although the centre of LV shows slightly leftward displacement. Since PE patients have sunken chest, a 3–4 cm may be the proper compression depth in the patients when considering the current compression guideline in normal subjects is 5–6 cm.
The association of serum antiphospholipid antibodies and dilute Russell's viper venom times
Authors: Froom Paul , Saffuri-Elias Enas , Rozenberg Orit , Barak Mira 
Published: December 2013

AimsWe hypothesised that there is a threshold value for the association of dilute Russell's viper venom times (dRVVT) with positive immunoglobin G antiphospholipid antibody (IgG-APLA) test results.MethodsWe tested 120 controls and a cohort of 2412 outpatients who had concomitant test results for dRVVT and IgG-APLA (IgG antibodies to cardiolipins and β2-glycoprotein I). We also selected a subgroup who had repeated IgG-APLA tests at least 12 weeks apart (1398 patients with multiple β2-glycoprotein I tests and 672 with multiple aCL tests). We cross tabulated the proportion of IgG-APLA single positive, double positive and persistently positive antibodies with dRVVT values.ResultsThe distribution of the dRVVT results from the reference population was consistent with an upper limit of the reference interval of 1.22 to >1.48. A consistent increase in the proportion of IgG-APLA single, double positive and persistently positive antibody tests occurred in the group with a normalised dRVVT ratio of 1.40–1.49. IgG-APLA double positivity was found in 12.5% (4 of 32) patients with a ratio of dRVVT 1.40–1.49 compared with 3.3% (6/181) of those with a ratio of dRVVT 1.20–1.39 (p=0.045).ConclusionsWe conclude that there is an association between dRVVT positivity and elevated proportions of single, double and persistently positive IgG-APLA test results with an apparent threshold effect. These findings may provide a general guide to risk and suggest a way to choose from a wide range of possible upper limits of the reference interval.