bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of FkpA as a Key Quality Control Factor for the Biogenesis of Outer Membrane Proteins under Heat Shock Conditions
Authors: Ge Xi , Lyu Zhi-Xin , Liu Yang , Wang Rui , Zhao Xin Sheng , Fu Xinmiao , Chang Zengyi 
Published: November 2013

ABSTRACT

The outer membrane proteins (OMPs) of Gram-negative bacterial cells, as well as the mitochondrion and chloroplast organelles, possess unique and highly stable β-barrel structures. Biogenesis of OMPs in
Escherichia coli
involves such periplasmic chaperones as SurA and Skp. In this study, we found that the Δ
surA
Δ
skp
double-deletion strain of
E. coli
, although lethal and defective in the biogenesis of OMPs at the normal growth temperature, is viable and effective at the heat shock temperature. We identified FkpA as the multicopy suppressor for the lethal phenotype of the Δ
surA
Δ
skp
strain. We also demonstrated that the deletion of
fkpA
from the Δ
surA
cells resulted in only a mild decrease in the levels of folded OMPs at the normal temperature but a severe decrease as well as lethality at the heat shock temperature, whereas the deletion of
fkpA
from the Δ
skp
cells had no detectable effect on OMP biogenesis at either temperature. These results strongly suggest a functional redundancy between FkpA and SurA for OMP biogenesis under heat shock stress conditions. Mechanistically, we found that FkpA becomes a more efficient chaperone for OMPs under the heat shock condition, with increases in both binding rate and affinity. In light of these observations and earlier reports, we propose a temperature-responsive OMP biogenesis mechanism in which the degrees of functional importance of the three chaperones are such that SurA > Skp > FkpA at the normal temperature but FkpA ≥ SurA > Skp at the heat shock temperature.
Identification of Legionella pneumophila Effectors Regulated by the LetAS-RsmYZ-CsrA Regulatory Cascade, Many of Which Modulate Vesicular Trafficking
Authors: Nevo Oded , Zusman Tal , Rasis Michal , Lifshitz Ziv , Segal Gil 
Published: November 2013

ABSTRACT

Legionella pneumophila
, the causative agent of Legionnaires' disease, is an intracellular human pathogen that utilizes the Icm/Dot type IVB secretion system to translocate a large repertoire of effectors into host cells. To find coregulated effectors, we performed a bioinformatic genomic screen with the aim of identifying effector-encoding genes containing putative CsrA regulatory elements. The regulation of these genes by the LetAS-RsmYZ-CsrA regulatory cascade was experimentally validated by examining their levels of expression in deletion mutants of relevant regulators and by site-directed mutagenesis of the putative CsrA sites. These analyses resulted in the identification of 26 effector-encoding genes regulated by the LetAS-RsmYZ-CsrA regulatory cascade, all of which were expressed at higher levels during the stationary phase. To determine if any of these effectors is involved in modulating the secretory pathway, they were overexpressed in wild-type yeast as well as in a yeast
sec22
deletion mutant, which encodes an R-SNARE that participates in the endoplasmic reticulum (ER)-Golgi trafficking. This examination identified many novel LetAS-RsmYZ-CsrA regulated effectors which are involved in this process. To further characterize the role of these 26 effectors in vesicular trafficking, they were examined in yeast
arf
and
arl
deletion mutants, which encode small GTPases that regulate ER-Golgi trafficking. This analysis revealed that the effectors examined manipulate different processes of the secretory pathway. Collectively, our results demonstrate that several of the
L. pneumophila
effectors which are coregulated in the bacterial cell are involved in the modulation of the same eukaryotic pathway.
Coordinated Expression of
fdxD
and Molybdenum Nitrogenase Genes Promotes Nitrogen Fixation by Rhodobacter capsulatus in the Presence of Oxygen
Authors: Hoffmann Marie-Christine , Müller Alexandra , Fehringer Maria , Pfänder Yvonne , Narberhaus Franz , Masepohl Bernd 
Published: November 2013

ABSTRACT

Rhodobacter capsulatus
is able to grow with N
2
as the sole nitrogen source using either a molybdenum-dependent or a molybdenum-free iron-only nitrogenase whose expression is strictly inhibited by ammonium. Disruption of the
fdxD
gene, which is located directly upstream of the Mo-nitrogenase genes,
nifHDK
, abolished diazotrophic growth via Mo-nitrogenase at oxygen concentrations still tolerated by the wild type, thus demonstrating the importance of FdxD under semiaerobic conditions. In contrast, FdxD was not beneficial for diazotrophic growth depending on Fe-nitrogenase. These findings suggest that the 2Fe2S ferredoxin FdxD specifically supports the Mo-nitrogenase system, probably by protecting Mo-nitrogenase against oxygen, as previously shown for its
Azotobacter vinelandii
counterpart, FeSII. Expression of
fdxD
occurred under nitrogen-fixing conditions, but not in the presence of ammonium. Expression of
fdxD
strictly required NifA1 and NifA2, the transcriptional activators of the Mo-nitrogenase genes, but not AnfA, the transcriptional activator of the Fe-nitrogenase genes. Expression of the
fdxD
and
nifH
genes, as well as the FdxD and NifH protein levels, increased with increasing molybdate concentrations. Molybdate induction of
fdxD
was independent of the molybdate-sensing regulators MopA and MopB, which repress
anfA
transcription at micromolar molybdate concentrations. In this report, we demonstrate the physiological relevance of an
fesII
-like gene,
fdxD
, and show that the cellular nitrogen and molybdenum statuses are integrated to control its expression.
SP10 Infectivity Is Aborted after Bacteriophage SP10 Infection Induces
nonA
Transcription on the Prophage SPβ Region of the Bacillus subtilis Genome
Authors: Yamamoto Tatsuya , Obana Nozomu , Yee Lii Mien , Asai Kei , Nomura Nobuhiko , Nakamura Kouji 
Published: November 2013

ABSTRACT

Bacteria have developed various strategies for phage resistance. Infection with phage induces the transcription of part of the phage resistance gene, but the regulatory mechanisms of such transcription remain largely unknown. The phage resistance gene
nonA
is located on the SPβ prophage region of the
Bacillus subtilis
Marburg strain genome. The
nonA
transcript was detected at the late stage of SP10 infection but is undetectable in noninfected cells. The
nonA
transcript was detected after the induction of the sigma factor Orf199-Orf200 (σ
Orf199-200
), when sigma factors encoded in the SP10 genome were expressed from a xylose-inducible plasmid. Thus, the SP10 sigma factor is an activator of a set of SP10 genes and
nonA
. The
nonA
gene encodes a 72-amino-acid protein with a transmembrane motif and has no significant homology with any protein in any database. NonA overexpression halted cell growth and reduced the efficiency of
B. subtilis
colony formation and respiration activity. In addition, SP10 virion protein synthesis was inhibited in the
nonA
+
strain, and SP10 virion particles were scarce in it. These results indicate that NonA is a novel protein that can abort SP10 infection, and its transcription was regulated by SP10 sigma factor.
Injury surveillance during a 2-day national female youth football tournament in Kenya
Authors: Lislevand Marianne , Andersen Thor Einar , Junge Astrid , Dvorak Jiri , Steffen Kathrin 
Published: November 2013

ObjectiveTo analyse the incidence, characteristics and circumstances of injuries during a female youth amateur football tournament in Kenya.Design14 injury recorders prospectively registered and classified all injuries during all matches. Four physiotherapists and two doctors supported the injury recorders.SettingA 2-day Mathare Youth Sports Association (MYSA) inter-provincial football tournament for female players in Nairobi, Kenya. The tournament is organised by a non-governmental organisation (NGO).Participants938 females divided into three age groups (under 13 years (U13), under 16 years (U16) and over 16 years (O16)).Main outcome measurementsOverall injury incidence.Results123 injuries occurred in 106 matches. The incidence of all injuries was 93.3 injuries/1000 h. Players in the U13 (relative risk (RR)=2.16, 95% CI 1.3 to 3.5; p=0.002) and U16 (RR=2.17, 95% CI 1.3 to 3.5; p=0.002) age groups had an increased risk of injury compared to the O16 group. Most injuries allowed the players to continue to play (n=98 of 121; 81%). For 15 (12%) of the injuries the player did not continue to play but was expected to fully participate in the following match, and eight of the injuries (6.1 injuries/1000 h) were expected to result in the player's absence from play for 1–7 days. The injuries most commonly affected the lower limb (n=100; 82%); contusions to the ankle (n=15; 12%) and foot/toe (n=15; 12%) were the most common specific injury types. Most acute injuries (89 of 113, 79%) were caused by player contact.ConclusionsThe incidence of injuries among female youth football players in a national tournament in Kenya was high, but time-loss injuries were rare. Playing football in a tournament organised by an NGO at the inter-provincial level was safe.
Change in objectively measured physical activity during the transition to adolescence
Authors: Corder Kirsten , Sharp Stephen J , Atkin Andrew J , Griffin Simon J , Jones Andrew P , Ekelund Ulf , van Sluijs Esther M F 
Published: November 2013

BackgroundPhysical activity (PA) declines during adolescence but change in different PA intensities across population subgroups is rarely explored. We describe change in sedentary (SED) time, light (LPA), moderate (MPA) and vigorous PA (VPA) assessed at three time points over 4 years.MethodsAccelerometer-assessed PA (min) was obtained at baseline (N=2064), 1 and 4 years later among British children (baseline mean±SD 10.2±0.3-year-old; 42.5% male). Change in SED (<100 counts/min (cpm)), LPA (101–1999 cpm), MPA (2000–3999 cpm) and VPA (≥4000 cpm) was studied using three-level (age, individual and school) mixed-effects linear regression including participants with data at ≥2 time points (N=990). Differences in change by sex, home location and weight status were explored with interactions for SED, LPA and moderate and vigorous PA (MVPA).ResultsSED increased by 10.6 (95% CI 9.1 to 12.2) min/day/year. MPA and VPA decreased by 1.4 (1.0 to 1.8) and 1.5 (1.1 to 1.8) min/day/year, respectively. VPA decreased more than MPA as a percentage of the baseline value. MVPA declined more steeply among boys (3.9 (3.0 to 4.8)) versus girls (2.0 (1.2 to 2.7) min/day/year) despite lower MVPA among girls at all ages; rural (4.4 (3.5 to 5.2)) versus urban individuals (1.3 (0.4 to 2.3) min/day/year) and on weekends (6.7 (5.2 to 8.1)) versus weekdays (2.8 (1.9 to 3.7) min/day/year). MVPA was consistently lower among overweight/obese individuals (−17.5 (−3.9 to −2.5) min/day/year).ConclusionsPA decreases and is replaced by SED during early adolescence in British youth. Results indicate the urgency of PA promotion among all adolescents but especially girls and in rural areas. Increasing VPA and targeting PA promotion during weekends appear important.
The orthopaedic error index: development and application of a novel national indicator for assessing the relative safety of hospital care using a cross-sectional approach
Authors: Panesar Sukhmeet S , Netuveli Gopalakrishnan , Carson-Stevens Andrew , Javad Sundas , Patel Bhavesh , Parry Gareth , Donaldson Liam J , Sheikh Aziz 
Published: November 2013

ObjectiveThe Orthopaedic Error Index for hospitals aims to provide the first national assessment of the relative safety of provision of orthopaedic surgery.DesignCross-sectional study (retrospective analysis of records in a database).SettingThe National Reporting and Learning System is the largest national repository of patient-safety incidents in the world with over eight million error reports. It offers a unique opportunity to develop novel approaches to enhancing patient safety, including investigating the relative safety of different healthcare providers and specialties.ParticipantsWe extracted all orthopaedic error reports from the system over 1 year (2009–2010).Outcome measuresThe Orthopaedic Error Index was calculated as a sum of the error propensity and severity. All relevant hospitals offering orthopaedic surgery in England were then ranked by this metric to identify possible outliers that warrant further attention.Results155 hospitals reported 48 971 orthopaedic-related patient-safety incidents. The mean Orthopaedic Error Index was 7.09/year (SD 2.72); five hospitals were identified as outliers. Three of these units were specialist tertiary hospitals carrying out complex surgery; the remaining two outlier hospitals had unusually high Orthopaedic Error Indexes: mean 14.46 (SD 0.29) and 15.29 (SD 0.51), respectively.ConclusionsThe Orthopaedic Error Index has enabled identification of hospitals that may be putting patients at disproportionate risk of orthopaedic-related iatrogenic harm and which therefore warrant further investigation. It provides the prototype of a summary index of harm to enable surveillance of unsafe care over time across institutions. Further validation and scrutiny of the method will be required to assess its potential to be extended to other hospital specialties in the UK and also internationally to other health systems that have comparable national databases of patient-safety incidents.
The comparative risk of new-onset diabetes after prescription of drugs for cardiovascular risk prevention in primary care: a national cohort study
Authors: Currie Olivia , Mangin Dee , Williman Jonathan , McKinnon-Gee Bianca , Bridgford Paul 
Published: November 2013

ObjectiveRecent studies suggest that statins increase the risk of subsequent diabetes with a clear dose response effect. However, patients prescribed statins have a higher background risk of diabetes. This national cohort study aims to provide an estimate of the comparative risks for subsequent development of new-onset diabetes in adults prescribed statins and in those with an already higher background risk on cardiovascular risk-modifying drugs and a control drug.DesignLongitudinal cohort study.SettingUse of routinely collected data from a complete national primary care electronic prescription database in New Zealand.Participants32 086 patients aged between 40 and 60 years in 2005 were eligible and assigned to four non-overlapping groups receiving their first prescription for: (1) diclofenac (healthy population) n=7140; (2) antihypertensives thought likely to induce diabetes (thiazides and β-blockers) n=5769; (3) antihypertensives thought less likely to induce diabetes (ACE inhibitors, angiotensin II receptor blockers, calcium channel blocker) n=6565 and (4) statins n=12 612.OutcomeNumbers of first metformin prescriptions were compared between these groups from 2006 to 2011.ResultsPatients prescribed statins have the highest risk of receiving a subsequent metformin prescription (HR 3.31; 95% CI 2.56 to 4.30; p<0.01), followed by patients prescribed antihypertensives thought less likely to induce diabetes (HR 2.32; 95% CI 1.74 to 3.09; p<0.01) and patients prescribed antihypertensives thought more likely to induce diabetes (HR 1.59; 95% CI 1.15 to 2.20; p<0.01) in the subsequent 6 years of follow-up, when compared to diclofenac.ConclusionsThese findings further support the link between statin use and new-onset diabetes and suggest that the understanding of diabetes risk associated with different antihypertensive drug classes may bear practice modification. This provides important information for future research, and for prescribers and patients when considering the risks and benefits of different types of cardiovascular risk-modifying drugs.
A three-year follow-up on the efficacy of psychosocial interventions for patients with mild dementia and their caregivers: the multicentre, rater-blinded, randomised Danish Alzheimer Intervention Study (DAISY)
Authors: Phung Kieu T T , Waldorff F B , Buss D V , Eckermann A , Keiding N , Rishøj S , Siersma V , Sørensen J , Søgaard R , Sørensen L V , Vogel A , Waldemar G 
Published: November 2013

ObjectivesTo examine the long-term efficacy at the 36-month follow-up of an early psychosocial counselling and support programme lasting 8–12 months for community-dwelling patients with mild Alzheimer's disease and their caregivers.DesignMulticentre, randomised, controlled, rater-blinded trial.SettingPrimary care and memory clinics in five Danish districts.Participants330 home-dwelling patients with mild Alzheimer's disease and their primary caregivers (dyads).InterventionsDyads were randomised to receive intervention during the first year after diagnosis. Both intervention and control groups had follow-up visits at 3, 6, 12 and 36 months.Main outcome measuresPrimary outcomes for the patients assessed at 36-month follow-up were changes from baseline in global cognitive function (Mini-Mental State Examination), depressive symptoms (Cornell Depression Scale) and proxy-rated EuroQoL quality of life on visual analogue scale. The primary outcomes for the caregivers were changes from baseline in depressive symptoms (Geriatric Depression Scale) and self-rated EuroQoL quality of life on a visual analogue scale. The secondary outcome measures for the patient were proxy-rated Quality of Life Scale for Alzheimer's disease (QoL-AD), Neuropsychiatric Inventory-Questionnaire, Alzheimer's disease Cooperative Study Activities of Daily Living Scale, all-cause mortality and nursing home placement.ResultsAt a 36-month follow-up, 2 years after the completion of the Danish Alzheimer Intervention Study (DAISY), the unadjusted positive effects previously detected at the 12-month follow-up in one patient primary outcome (Cornell depression score) and one patient secondary outcome (proxy-rated QoL-AD) disappeared (Cornell depression score, p=0.93; proxy-rated QoL-AD, p=0.81). No long-term effect of DAISY intervention on any other primary and secondary outcomes was found at the 36-month follow-up.ConclusionsFor patients with very mild Alzheimer's disease and their caregivers, an intensive, multi-component, semitailored psychosocial intervention programme with counselling, education and support during the first year after diagnosis did not show any positive long-term effect on primary and secondary outcomes.Trial registrationThe study was registered in the Clinical Trial Database (http://www.controlled-trials.com/ISRCTN74848736).
Improving the investigation of suspected deep vein thrombosis in the Emergency Department
Authors: Daum Peter 
Published: November 2013

AbstractDeep vein thrombosis is an important medical condition that requires treatment to prevent further complications. However, diagnosing deep vein thrombosis is not straightforward because its symptoms can mimic a number of alternative diagnoses - often leading to unnecessary investigation. The latest NICE guidance published in June 2012 provides a clear evidence-based approach to diagnosis which helps to minimise this potential loss of valuable time and resources.It was recognised that the Emergency Department was unaware of the latest guidance and demonstrated that it was often over and inadequately investigating suspected deep vein thromboses, unnecessarily using resources and putting patients at risk. To address this, a new investigation pathway and proforma were introduced into the department. It was placed onto the Trust website and incorporated into the departmental induction for new staff and trainees.Following the introduction of these changes, a re-audit demonstrated that the department's investigation of deep vein thrombosis improved significantly. In addition to increased adherence to the latest guidelines and improved documentation there was a 21% reduction in the total number of ultrasound scans performed indicating a significant impact upon both the department and patient care.
Poverty's latent effect on adiposity during childhood: evidence from a Québec birth cohort
Authors: Kakinami Lisa , Séguin Louise , Lambert Marie , Gauvin Lise , Nikiema Béatrice , Paradis Gilles 
Published: November 2013

BackgroundChildhood poverty heightens the risk of obesity in adulthood, but the age at which this risk appears is unclear. We analysed the association between poverty trajectories with body mass index (BMI) Z-scores or the risk of being overweight or obese across four ages (6 years, 8 years, 10 years and 12 years) in childhood.MethodsData were from the 1998–2010 ‘Quebec Longitudinal Study of Child Development’ cohort (n=698). Poverty was defined using Statistics Canada's thresholds, and trajectories were characterised with a Latent Class Growth Analysis. Multivariable linear and logistic regression models adjusted for sex, whether the mother was an immigrant, maternal education and birth weight.ResultsFour income trajectories were identified: a reference group (stable non-poor), and 3 higher exposure categories (increasing likelihood of poverty, decreasing likelihood of poverty or stable poor). Compared with children from stable non-poor households, children from stable poor households had BMI Z-scores that were 0.39 and 0.43 larger than children from stable non-poor households at age 10 years and 12 years, respectively (p<0.05). Compared with children from stable non-poor households, children from stable poor households were 2.22, 2.34, and 3.04 times more likely to be overweight or obese at age 8 years, 10 years and 12 years, respectively (p<0.05).ConclusionA latency period for the detrimental effects of child poverty on the risk of overweight or obesity was detected. Whether the effects continue to widen with increasing duration of exposure to poverty as the children age should be investigated.
Extreme temperatures and paediatric emergency department admissions
Authors: Xu Zhiwei , Hu Wenbiao , Su Hong , Turner Lyle R , Ye Xiaofang , Wang Jiajia , Tong Shilu 
Published: November 2013

BackgroundChildren are particularly vulnerable to the effects of extreme temperatures.ObjectiveTo examine the relationship between extreme temperatures and paediatric emergency department admissions (EDAs) in Brisbane, Australia, during 2003–2009.MethodsA quasi-Poisson generalised linear model combined with a distributed lag non-linear model was used to examine the relationships between extreme temperatures and age-, gender- and cause-specific paediatric EDAs, while controlling for air pollution, relative humidity, day of the week, influenza epidemics, public holiday, season and long-term trends. The model residuals were checked to identify whether there was an added effect due to heat waves or cold spells.ResultsThere were 131 249 EDAs among children during the study period. Both high (RR=1.27; 95% CI 1.12 to 1.44) and low (RR=1.81; 95% CI 1.66 to 1.97) temperatures were significantly associated with an increase in paediatric EDAs in Brisbane. Male children were more vulnerable to temperature effects. Children aged 0–4 years were more vulnerable to heat effects and children aged 10–14 years were more sensitive to both hot and cold effects. High temperatures had a significant impact on several paediatric diseases, including intestinal infectious diseases, respiratory diseases, endocrine, nutritional and metabolic diseases, nervous system diseases and chronic lower respiratory diseases. Low temperatures were significantly associated with intestinal infectious diseases, respiratory diseases and endocrine, nutritional and metabolic diseases. An added effect of heat waves on childhood chronic lower respiratory diseases was seen, but no added effect of cold spells was found.ConclusionsAs climate change continues, children are at particular risk of a variety of diseases which might be triggered by extremely high temperatures. This study suggests that preventing the effects of extreme temperature on children with respiratory diseases might reduce the number of EDAs.