bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Life Cycle of ComS, the Competence-Stimulating Peptide of Streptococcus thermophilus
Authors: Gardan Rozenn , Besset Colette , Gitton Christophe , Guillot Alain , Fontaine Laetitia , Hols Pascal , Monnet Véronique 
Published: February 2013

ABSTRACT

In streptococci, ComX is the alternative sigma factor controlling the transcription of the genes encoding the genetic transformation machinery. In
Streptococcus thermophilus
,
comX
transcription is controlled by a complex consisting of a transcriptional regulator of the Rgg family, ComR, and a signaling peptide, ComS, which controls ComR activity. Following its initial production, ComS is processed, secreted, and imported back into the cell by the Ami oligopeptide transporter. We characterized these steps and the partners interacting with ComS during its extracellular circuit in more detail. We identified the mature form of ComS and demonstrated the involvement of the membrane protease Eep in ComS processing. We found that ComS was secreted but probably not released into the extracellular medium. Natural competence was first discovered in a chemically defined medium without peptides. We show here that the presence of a high concentration of nutritional peptides in the medium prevents the triggering of competence. In milk, the ecological niche of
S. thermophilus
, competence was found to be functional, suggesting that the concentration of nutritional peptides was too low to interfere with ComR activation. The kinetics of expression of the
comS
,
comR
, and
comX
genes and of a late competence gene,
dprA
, in cultures inoculated at different initial densities revealed that the activation mechanism of ComR by ComS is more a timing device than a quorum-sensing mechanism sensu stricto. We concluded that the ComS extracellular circuit facilitates tight control over the triggering of competence in
S. thermophilus
.
Expression Level of Bacillus subtilis Germinant Receptors Determines the Average Rate but Not the Heterogeneity of Spore Germination
Authors: Zhang Jing-qiao , Griffiths Keren K. , Cowan Ann , Setlow Peter , Yu Ji 
Published: February 2013

ABSTRACT

Germination of
Bacillus subtilis
spores can be triggered by the binding of specific nutrients, called germinants, to germinant receptors (GRs) in the spore's inner membrane. This interaction eventually initiates, with variable time delays, the release of dipicolinic acid and cations from the spore core—a key step in spore germination. The kinetics of this process are highly heterogeneous for individual spores. In this work, we sought to investigate how the germination heterogeneity was controlled. In particular, we tested whether the rates of germination were determined by GR levels, which vary from spore to spore due to stochastic gene expression. Both the expression levels of GRs and the germination rate were measured in single spores, and the experimental results were compared to theoretical predictions. Our results indicated that the variation in the expression levels of GRs was not the primary factor that controls spore germination heterogeneity. Two alternative hypotheses are discussed in light of this experimental discovery.
Protein Kinase/Phosphatase Function Correlates with Gliding Motility in Mycoplasma pneumoniae
Authors: Page Clinton A. , Krause Duncan C. 
Published: February 2013

ABSTRACT

Mycoplasma pneumoniae
exhibits a novel form of gliding motility that is mediated by the terminal organelle, a differentiated polar structure. Given that genes known to be involved in gliding in other organisms are absent in
M. pneumoniae
, random transposon mutagenesis was employed to generate mutants with gliding-deficient phenotypes. Transposon insertions in the only annotated Ser/Thr protein kinase gene (
prkC
; MPN248) and its cognate phosphatase gene (
prpC
; MPN247) in
M. pneumoniae
resulted in significant and contrasting effects on gliding frequencies.
prkC
mutant cells glided at approximately half the frequency of wild-type cells, while
prpC
mutant cells glided more than twice as frequently as wild-type cells. Phosphoprotein staining confirmed the association between phosphorylation of the cytoskeletal proteins HMW1 and HMW2 and membrane protein P1 and the gliding phenotype. When the
prpC
mutant was complemented by transposon delivery of a wild-type copy of the
prpC
allele, gliding frequencies and phosphorylation levels returned to the wild-type standard. Surprisingly, delivery of the recombinant wild-type
prkC
allele dramatically increased gliding frequency to a level approximately 3-fold greater than that of wild-type in the
prkC
mutant. Collectively, these data suggest that PrkC and PrpC work in opposition in
M. pneumoniae
to influence gliding frequency.
Is socioeconomic status associated with dietary sodium intake in Australian children? A cross-sectional study
Authors: Grimes Carley A , Campbell Karen J , Riddell Lynn J , Nowson Caryl A 
Published: February 2013

ObjectiveTo assess the association between socioeconomic status (SES) and dietary sodium intake, and to identify if the major dietary sources of sodium differ by socioeconomic group in a nationally representative sample of Australian children.DesignCross-sectional survey.Setting2007 Australian National Children's Nutrition and Physical Activity Survey.ParticipantsA total of 4487 children aged 2–16 years completed all components of the survey.Primary and secondary outcome measuresSodium intake was determined via one 24 h dietary recall. The population proportion formula was used to identify the major sources of dietary salt. SES was defined by the level of education attained by the primary carer. In addition, parental income was used as a secondary indicator of SES.ResultsDietary sodium intake of children of low SES background was 2576 (SEM 42) mg/day (salt equivalent 6.6 (0.1) g/day), which was greater than that of children of high SES background 2370 (35) mg/day (salt 6.1 (0.1) g/day; p<0.001). After adjustment for age, gender, energy intake and body mass index, low SES children consumed 195 mg/day (salt 0.5 g/day) more sodium than high SES children (p<0.001). Low SES children had a greater intake of sodium from processed meat, gravies/sauces, pastries, breakfast cereals, potatoes and potato snacks (all p<0.05).ConclusionsAustralian children from a low SES background have on average a 9% greater intake of sodium from food sources compared with those from a high SES background. Understanding the socioeconomic patterning of salt intake during childhood should be considered in interventions to reduce cardiovascular disease.
Diagnosis-specific disability pension predicts suicidal behaviour and mortality in young adults: a nationwide prospective cohort study
Authors: Jonsson Ulf , Alexanderson Kristina , Kjeldgård Linnea , Westerlund Hugo , Mittendorfer-Rutz Ellenor 
Published: February 2013

ObjectivesIncreasing rates of disability pension (DP), particularly owing to mental diagnoses, have been observed among young adults in Organisation for Economic Co-operation and Development (OECD) countries. There is a lack of knowledge about the health prognosis in this group. The aim of this study was to investigate whether DP in young adulthood owing to specific mental diagnoses or somatic diagnoses predicts suicidal behaviour and all-cause mortality.DesignA nationwide prospective cohort study.SettingA register study of all young adults who in 2005 were 19–23 years old and lived in Sweden. Registers held by the National Board of Health and Welfare, Statistics Sweden and the National Social Insurance Agency were used.Participants525 276 young adults. Those who in 2005 had DP with mental diagnoses (n=8070) or somatic diagnoses (n=3975) were compared to all the other young adults in the same age group (n=513 231).Outcome measuresHRs for suicide attempt, suicide and all-cause mortality in 2006–2010 were calculated by Cox proportionate hazard regression models, adjusted for sex, country of birth, parental education and parental and previous own suicidal behaviour.ResultsThe adjusted HR for suicide attempt was 3.32 (95% CI 2.98 to 3.69) among those on DP with mental diagnoses and 1.78 (95% CI 1.41 to 2.26) among those on DP with somatic diagnoses. For the specific mental diagnoses, the unadjusted HRs ranged between 2.42 (mental retardation) and 22.94 (personality disorders), while the adjusted HRs ranged between 2.03 (mental retardation) and 6.00 (bipolar disorder). There was an increased risk of mortality for young adults on DP in general, but only those with mental DP diagnoses had a significantly elevated HR of completed suicide with an adjusted HR of 3.92 (95% CI 2.83 to 5.43).ConclusionsYoung adults on DP are at increased risk of suicidal behaviour and preterm death, which emphasises the need for improved treatment and follow-up.
Life-event stress induced by the Great East Japan Earthquake was associated with relapse in ulcerative colitis but not Crohn's disease: a retrospective cohort study
Authors: Shiga Hisashi , Miyazawa Teruko , Kinouchi Yoshitaka , Takahashi Seiichi , Tominaga Gen , Takahashi Hiroki , Takagi Sho , Obana Nobuya , Kikuchi Tatsuya , Oomori Shinya , Nomura Eiki , Shiraki Manabu , Sato Yuichirou , Takahashi Shuichiro , Umemura Ken , Yokoyama Hiroshi , Endo Katsuya , Kakuta Yoichi , Aizawa Hiroki , Matsuura Masaki , Kimura Tomoya , Kuroha Masatake , Shimosegawa Tooru 
Published: February 2013

ObjectiveStress is thought to be one of the triggers of relapses in patients with inflammatory bowel disease (IBD). We examined the rate of relapse in IBD patients before and after the Great East Japan Earthquake.DesignA retrospective cohort study.Settings13 hospitals in Japan.Participants546 ulcerative colitis (UC) and 357 Crohn's disease (CD) patients who received outpatient and inpatient care at 13 hospitals located in the area that were seriously damaged by the earthquake. Data on patient's clinical characteristics, disease activity and deleterious effects of the earthquake were obtained from questionnaires and hospital records.Primary outcomeWe evaluated the relapse rate (from inactive to active) across two consecutive months before and two consecutive months after the earthquake. In this study, we defined ‘active’ as conditions with a partial Mayo score=2 or more (UC) or a Harvey-Bradshaw index=6 or more (CD).ResultsAmong the UC patients, disease was active in 167 patients and inactive in 379 patients before the earthquake. After the earthquake, the activity scores increased significantly (p<0.0001). A total of 86 patients relapsed (relapse rate=15.8%). The relapse rate was about twice that of the corresponding period in the previous year. Among the CD patients, 86 patients had active disease and 271 had inactive disease before the earthquake. After the earthquake, the activity indices changed little. A total of 25 patients experienced a relapse (relapse rate=7%). The relapse rate did not differ from that of the corresponding period in the previous year. Multivariate analyses revealed that UC, changes in dietary oral intake and anxiety about family finances were associated with the relapse.ConclusionsLife-event stress induced by the Great East Japan Earthquake was associated with relapse in UC but not CD.
Contextual information influences diagnosis accuracy and decision making in simulated emergency medicine emergencies
Authors: McRobert Allistair Paul , Causer Joe , Vassiliadis John , Watterson Leonie , Kwan James , Williams Mark A 
Published: February 2013

BackgroundIt is well documented that adaptations in cognitive processes with increasing skill levels support decision making in multiple domains. We examined skill-based differences in cognitive processes in emergency medicine physicians, and whether performance was significantly influenced by the removal of contextual information related to a patient's medical history.MethodSkilled (n=9) and less skilled (n=9) emergency medicine physicians responded to high-fidelity simulated scenarios under high- and low-context information conditions.ResultsSkilled physicians demonstrated higher diagnostic accuracy irrespective of condition, and were less affected by the removal of context-specific information compared with less skilled physicians. The skilled physicians generated more options, and selected better quality options during diagnostic reasoning compared with less skilled counterparts. These cognitive processes were active irrespective of the level of context-specific information presented, although high-context information enhanced understanding of the patients’ symptoms resulting in higher diagnostic accuracy.ConclusionsOur findings have implications for scenario design and the manipulation of contextual information during simulation training.
Homicides of law enforcement officers responding to domestic disturbance calls
Authors: Kercher Cassandra , Swedler David I , Pollack Keshia M , Webster Daniel W 
Published: February 2013

ObjectiveTo describe the law enforcement officer (LEO), encounter, perpetrator and victim characteristics of domestic disturbance-related LEO homicides in the USA from 1996 to 2010.MethodsNarrative text analysis was conducted on the Federal Bureau of Investigation's annual report ‘Law Enforcement Officers Killed and Assaulted’. Potential cases were confirmed if the narrative included the term ‘domestic disturbance’ or a domestic disturbance situation was described.Results116 LEOs were killed while responding to domestic disturbance calls. Ninety-five per cent of these homicides were committed with a firearm. Sixty-seven per cent of LEOs were wearing body armour when killed; however, 52% received the fatal wound to the head/neck. Sixty-one per cent of suspects had a criminal history mentioned within the narratives and perpetrators of intimate partner violence (IPV) were more likely to be killed by LEOs than suspects involved in other forms of domestic violence. Victims of the domestic disturbance were killed in 21% of the IPV-related LEO homicide cases as opposed to only 5% of other domestic disturbance calls. A firearm was the most common weapon used in the murder of a domestic disturbance victim (86%).ConclusionsThis study describes domestic disturbance-related LEO homicides. Future research in this area should further examine the dangers unique to domestic disturbance calls. A longitudinal analysis could provide greater understanding of the injury and mortality risks faced by LEOs, in order to inform homicide prevention among law enforcement.
Targeted Cancer Therapy with a 2-Deoxyglucose–Based Adriamycin Complex
Authors: Cao Jie , Cui Sisi , Li Siwen , Du Changli , Tian Junmei , Wan Shunan , Qian Zhiyu , Gu Yueqing , Chen Wei R. , Wang Guangji 
Published: February 2013

Abstract
Adriamycin (ADM) has been effective against many types of solid tumors in clinical applications. However, its use is limited because of systemic toxicities, primarily cardiotoxicity, and multidrug resistance. In this study, a new active receptor-mediated complex, ADM conjugated with 2-amino-2-deoxy-d-glucose and succinic acid (2DG–SUC–ADM), was designed to target tumor cells through glucose transporter 1 (GLUT1). MTT assay and confocal images showed that the complex had better inhibition rate to tumor cells and low toxicity to normal cells. Most importantly, the complex displayed a potential to reverse overcome multidrug resistance in cancer cells, with more complex transported into the nucleus of tumor cells. Our in vivo experiments also showed that this new complex could significantly decrease organ toxicity and enhance the antitumor efficacy compared with free ADM, indicating a promising drug of 2DG–SUC–ADM for targeted cancer therapy. Cancer Res; 73(4); 1362–73. ©2012 AACR.
scFv-Based “Grababody” as a General Strategy to Improve Recruitment of Immune Effector Cells to Antibody-Targeted Tumors
Authors: Cai Zheng , Fu Ting , Nagai Yasuhiro , Lam Lian , Yee Marla , Zhu Zhiqiang , Zhang Hongtao 
Published: February 2013

AbstractRecruitment of immune cells to tumor cells targeted by a therapeutic antibody can heighten the antitumor efficacy of the antibody. For example, p185her2/neu-targeting antibodies not only downregulate the p185her2/neu kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) through the antibody Fc region. Here, we describe a generalized strategy to improve immune cell recruitment to targeted cancer cells, using a modified scFv antibody we call a “Grababody” that binds the target protein and endogenous immunoglobulins. The model system we used to illustrate the use of this platform recognizes p185her2/neu and includes an IgG binding domain. The recombinant scFv Grababody that was created recruited circulating human IgGs and attracted immune cells carrying Fc receptors to tumor cells that expressed p185her2/neu. The presence of the IgG binding domain significantly enhanced CDC and ADCC activity and improved antitumor activity in vivo. Our results illustrate a novel general approach to improve antibody-like proteins for therapeutic applications. Cancer Res; 73(8); 2619–27. ©2013 AACR.
Association of AMP-Activated Protein Kinase with Risk and Progression of Non–Hodgkin Lymphoma
Authors: Hoffman Aaron E. , Demanelis Kathryn , Fu Alan , Zheng Tongzhang , Zhu Yong 
Published: February 2013

AbstractBackground: Metabolic dysregulation has been identified as an “emerging hallmark” of cancer. The heterotrimeric AMP-activated protein kinase (AMPK) complex is a central regulator of the metabolic system and an important component of the mTOR pathway and the p53 axis, making it uniquely positioned to influence carcinogenesis through its canonical functions in the metabolic arena, as well as through more traditional mechanisms such as regulation of apoptosis and angiogenesis.Methods: We conducted a population-based genetic association study to examine the impact of mutations in AMPK subunit genes on risk of non–Hodgkin lymphoma (NHL). We also analyzed public microarray data to determine the expression of AMPK in NHL cells and to assess the influence of AMPK expression on overall survival in patients with NHL.Results: We identified an AMPK subunit haplotype, which was significantly associated with NHL [OR, 5.44, 95% confidence interval (CI), 2.15–13.75] in women with no family history of cancer. Haplotypes in two subunits, PRKAA2 and PRKAG3, were nominally associated with the follicular and diffuse large B-cell lymphoma histologic subtypes, respectively, although these associations did not retain statistical significance after correction for multiple comparisons. Further, both of these subunits were differentially expressed (P &lt; 0.05) in one or more lymphoma cell type, and higher expression of two versions of the AMPK-β subunit was significantly associated with increased 5-year survival among patients with NHL (P = 0.001 and P = 0.021).Conclusion: These results provide evidence for AMPK involvement in the pathogenesis and progression of NHL.Impact: These findings may lead to a novel area of research into NHL treatment and chemoprevention. Cancer Epidemiol Biomarkers Prev; 22(4); 736–44. ©2013 AACR.
Metabolomics in Epidemiology: Sources of Variability in Metabolite Measurements and Implications
Authors: Sampson Joshua N. , Boca Simina M. , Shu Xiao Ou , Stolzenberg-Solomon Rachael Z. , Matthews Charles E. , Hsing Ann W. , Tan Yu Ting , Ji Bu-Tian , Chow Wong-Ho , Cai Qiuyin , Liu Da Ke , Yang Gong , Xiang Yong Bing , Zheng Wei , Sinha Rashmi , Cross Amanda J. , Moore Steven C. 
Published: February 2013

Abstract
Background: Metabolite levels within an individual vary over time. This within-individual variability, coupled with technical variability, reduces the power for epidemiologic studies to detect associations with disease. Here, the authors assess the variability of a large subset of metabolites and evaluate the implications for epidemiologic studies.
Methods: Using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography-mass spectroscopy (GC/MS) platforms, 385 metabolites were measured in 60 women at baseline and year-one of the Shanghai Physical Activity Study, and observed patterns were confirmed in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening study.
Results: Although the authors found high technical reliability (median intraclass correlation = 0.8), reliability over time within an individual was low. Taken together, variability in the assay and variability within the individual accounted for the majority of variability for 64% of metabolites. Given this, a metabolite would need, on average, a relative risk of 3 (comparing upper and lower quartiles of “usual” levels) or 2 (comparing quartiles of observed levels) to be detected in 38%, 74%, and 97% of studies including 500, 1,000, and 5,000 individuals. Age, gender, and fasting status factors, which are often of less interest in epidemiologic studies, were associated with 30%, 67%, and 34% of metabolites, respectively, but the associations were weak and explained only a small proportion of the total metabolite variability.
Conclusion: Metabolomics will require large, but feasible, sample sizes to detect the moderate effect sizes typical for epidemiologic studies.
Impact: We offer guidelines for determining the sample sizes needed to conduct metabolomic studies in epidemiology. Cancer Epidemiol Biomarkers Prev; 22(4); 631–40. ©2013 AACR.
HOXB13 Mutation and Prostate Cancer: Studies of Siblings and Aggressive Disease
Authors: Witte John S. , Mefford Joel , Plummer Sarah J. , Liu Jinghua , Cheng Iona , Klein Eric A. , Rybicki Benjamin A. , Casey Graham 
Published: February 2013

Abstract
Background: Recent work detected for the first time a high-risk prostate cancer mutation, in homeobox B13 (HOXB13) among European-Americans.
Methods: We further evaluated this G84E missense mutation (rs138213197) in two genetic association studies of prostate cancer: a family-based study of brothers and a case–control study of more aggressive disease (N = 2,665 total). We then calculated overall impact of this mutation by pooling all published studies of European-Americans.
Results: In our studies, the mutation was found exclusively among men with prostate cancer (carrier frequency = 1.48%) or unaffected brothers of cases carrying the mutation (frequency = 0.34%), and carrying the mutation gave an OR for disease = 4.79 (P = 0.01). The G84E mutation was more common among men with an earlier age of onset (≤55 years) or a family history of prostate cancer. We also observed for the first time an African-American case carrying the G84E mutation, although at HOXB13 both of his chromosomes were of European-American ancestry. The pooled analysis also indicated that carrying the G84E mutation results in an almost five-fold increase in risk of prostate cancer (P = 3.5 × 10−17), and this risk is even higher among cases with an early age of prostate cancer onset (≤55 years) or a family history of disease: a test of heterogeneity across these strata gives P &lt; 1 × 10−5.
Conclusions: The HOXB13 mutation substantially increases risk of early onset, familial prostate cancer in European-American men.
Impact: Testing for the G84E mutation in men with a positive family history may help distinguish those who merit more regular screening for prostate cancer. Cancer Epidemiol Biomarkers Prev; 22(4); 675–80. ©2013 AACR.