bluuebunny/crossref_metadata_2025_split huggingface dataset:
Damage of Streptococcus mutans biofilms by carolacton, a secondary metabolite from the myxobacterium Sorangium cellulosum
Authors: Kunze Brigitte , Reck Michael , Dötsch Andreas , Lemme André , Schummer Dietmar , Irschik Herbert , Steinmetz Heinrich , Wagner-Döbler Irene 
Published: August 2010

Abstract

Background

Streptococcus mutans is a major pathogen in human dental caries. One of its important virulence properties is the ability to form biofilms (dental plaque) on tooth surfaces. Eradication of such biofilms is extremely difficult. We therefore screened a library of secondary metabolites from myxobacteria for their ability to damage biofilms of S. mutans.

Results
Here we show that carolacton, a secondary metabolite isolated from Sorangium cellulosum, has high antibacterial activity against biofilms of S. mutans. Planktonic growth of bacteria was only slightly impaired and no acute cytotoxicity against mouse fibroblasts could be observed. Carolacton caused death of S. mutans biofilm cells, elongation of cell chains, and changes in cell morphology. At a concentration of 10 nM carolacton, biofilm damage was already at 35% under anaerobic conditions. A knock-out mutant for comD, encoding a histidine kinase specific for the competence stimulating peptide (CSP), was slightly less sensitive to carolacton than the wildtype. Expression of the competence related alternate sigma factor ComX was strongly reduced by carolacton, as determined by a pcomX luciferase reporter strain.

Conclusions
Carolacton possibly interferes with the density dependent signalling systems in S. mutans and may represent a novel approach for the prevention of dental caries.
Short and long term outcome of neonatal hyperglycemia in very preterm infants: a retrospective follow-up study
Authors: van der Lugt N Margreth , Smits-Wintjens Vivianne EHJ , van Zwieten Paul HT , Walther Frans J 
Published: August 2010

AbstractBackgroundHyperglycemia in premature infants is associated with increased morbidity and mortality, but data on long-term outcome are limited. We investigated the effects of neonatal hyperglycemia (blood glucose ≥ 10 mmol/l, treated with insulin for ≥ 12 hours) on growth and neurobehavioral outcome at 2 years of age.MethodsRetrospective follow-up study at 2 years of age among 859 infants ≤32 weeks of gestation admitted to a tertiary neonatal center between January 2002 and December 2006. Thirty-three survivors treated with insulin for hyperglycemia and 63 matched controls without hyperglycemia were evaluated at a corrected age of 2 years. Outcome measures consisted of growth (weight, length, and head circumference) and neurological and behavioural development.Results66/859 (8%) infants ≤ 32 weeks of gestation developed hyperglycemia. Mortality during admission was 27/66 (41%) in the hyperglycemia group versus 62/793 (8%) in those without hyperglycemia (p < 0.001). Mortality was higher in infants with hyperglycemia with a birth weight ≤1,000 gram (p = 0.005) and/or gestational age of 24-28 weeks (p = 0.009) than in control infants without hyperglycemia. Sepsis was more prominent in infants with hyperglycemia and a birth weight of >1,000 gram (p = 0.002) and/or gestational age of 29-32 weeks (p = 0.009) than in control infants without hyperglycemia. Growth at 2 years of age was similar, but neurological and behavioural development was more frequently abnormal among those with neonatal hyperglycemia (p = 0.036 and 0.021 respectively).ConclusionsMortality was higher in very preterm infants with hyperglycemia treated with insulin during the neonatal period. At 2 years of age survivors showed normal growth, but a higher incidence of neurological and behavioural problems. Better strategies to manage hyperglycemia may improve outcome of very preterm infants.
A systematic review of evidence for the added benefits to health of exposure to natural environments
Authors: Bowler Diana E , Buyung-Ali Lisette M , Knight Teri M , Pullin Andrew S 
Published: August 2010

AbstractBackgroundThere is increasing interest in the potential role of the natural environment in human health and well-being. However, the evidence-base for specific and direct health or well-being benefits of activity within natural compared to more synthetic environments has not been systematically assessed.MethodsWe conducted a systematic review to collate and synthesise the findings of studies that compare measurements of health or well-being in natural and synthetic environments. Effect sizes of the differences between environments were calculated and meta-analysis used to synthesise data from studies measuring similar outcomes.ResultsTwenty-five studies met the review inclusion criteria. Most of these studies were crossover or controlled trials that investigated the effects of short-term exposure to each environment during a walk or run. This included 'natural' environments, such as public parks and green university campuses, and synthetic environments, such as indoor and outdoor built environments. The most common outcome measures were scores of different self-reported emotions. Based on these data, a meta-analysis provided some evidence of a positive benefit of a walk or run in a natural environment in comparison to a synthetic environment. There was also some support for greater attention after exposure to a natural environment but not after adjusting effect sizes for pretest differences. Meta-analysis of data on blood pressure and cortisol concentrations found less evidence of a consistent difference between environments across studies.ConclusionsOverall, the studies are suggestive that natural environments may have direct and positive impacts on well-being, but support the need for investment in further research on this question to understand the general significance for public health.
Up-regulation of p21 and TNF-α is mediated in lycorine-induced death of HL-60 cells
Authors: Liu Jing , Hu Ji-liang , Shi Bi-Wei , He Yan , Hu Wei-Xin 
Published: August 2010

Abstract

Background
Leukemia is one of the most life-threatening cancers today, and acute promyelogenous leukemia (APL) is a common type of leukemia. Many natural compounds have already been found to exhibit significant anti-tumor effects. Lycorine, a natural alkaloid extracted from Amaryllidaceae, exhibited anti-leukemia effects in vitro and in vivo. The survival rate of HL-60 cells exposed to lycorine was decreased, cell growth was slowed down, and cell regeneration potential was inhibited. HL-60 cells exhibited typical apoptotic characteristic. Lycorine can suppress leukemia growth and reduce cell survival and inducing apoptosis of tumor cells. The purpose of this work is to elucidate the mechanism by which lycorine induces APL cells.

Results
When HL-60 cells were treated with different concentration of lycorine, the expression of p21 and TNF-α was up-regulated in a concentration-dependent manner as shown by real-time quantitative reverse transcriptase-polymerase chain reaction and Western blotting. Lycorine also down-regulated p21-related gene expression, including Cdc2, Cyclin B, Cdk2 and Cyclin E, promoted Bid truncation, decreased IκB phosphorylation and blocked NF-κB nuclear import. Cytochrome c was released from mitochondria as observed with confocal laser microscopy.

Conclusions
The TNF-α signal transduction pathway and p21-mediated cell-cycle inhibition were involved in the apoptosis of HL-60 cells induced by lycorine. These results contribute to the development of new lycorine-based anti-leukemia drugs.
The defensive alliance between neutrophils and NK cells as a novel arm of innate immunity
Authors: Costantini Claudio , Cassatella Marco A 
Published: August 2010

ABSTRACTThe immune system is equipped with a plethora of mechanisms that protect the host from the harmful effects of environmental insults. However, the traditional “hierarchical” view of the immune response, in which innate, “nonspecific” cells are first recruited to the site of damage, before the highly “specific”, adaptive immune response develops, has been questioned recently. First, the innate response is much more specific than recognized previously: indeed, each cell of the innate system is not only endowed with an ever-expanding array of germ-line-encoded receptors, which differentiate between distinct insults, but also is modulated continuously by other leukocytes that concomitantly interact with and respond to that particular insult. The other reason is that the cells of the innate system are instrumental for the adaptive system to accomplish its function, as they can also modulate the activity of lymphocytes reciprocally during the entire course of the immune response. This complex pattern of interactions is illustrated by recent advances on the functions of PMNs, clearly showing that unexpectedly, these cells also contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Herein, given the peculiar role of neutrophils and NK cells in inflammation, clearance of pathogens/viral-infected cells, and cancer immunosurveillance, we summarize the current knowledge about the mechanisms whereby neutrophils and NK cells interact and regulate the activities of one another, as well as discuss their potential implications involved in the pathogenesis of chronic, inflammatory pathologies, infections, and tumors.
The C-terminal acidic tail is responsible for the inhibitory effects of HMGB1 on efferocytosis
Authors: Banerjee Sami , Friggeri Arnaud , Liu Gang , Abraham Edward 
Published: August 2010

Abstract
The HMGB1 C-terminal tail is responsible for the in vitro and in vivo inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils.
HMGB1 was described originally as a nuclear protein involved in DNA binding and transcriptional regulation. However, HMGB1 also has an extracellular role as a potent mediator of inflammation and can diminish the uptake of apoptotic cells by phagocytes, a process called efferocytosis. To explore the mechanism responsible for the ability of HMGB1 to inhibit efferocytosis, we examined the role of the C-terminal acidic tail, a region of HMGB1 that has been shown to participate in specific intramolecular interactions. Deletion of the C-terminal tail abrogated the ability of HMGB1 to decrease murine macrophage ingestion of apoptotic neutrophils and to diminish phagocytosis-induced activation of Erk and Rac-1 in macrophages. We found that RAGE plays a major role in efferocytosis, and deletion of the C-terminal tail of HMGB1 prevented binding of HMGB1 to RAGE but not to other macrophage receptors involved in efferocytosis, such as the αVβ3 integrin. Whereas HMGB1 decreased ingestion of apoptotic neutrophils significantly by alveolar macrophages under in vivo conditions in the lungs of mice, this effect was lost when the C-terminal acidic tail was absent from HMGB1. These results demonstrate that the HMGB1 C-terminal tail is responsible for the inhibitory effects of HMGB1 on phagocytosis of apoptotic neutrophils under in vitro and in vivo conditions.
Evasion of natural killer cells by influenza virus
Authors: Guo Hailong , Kumar Pawan , Malarkannan Subramaniam 
Published: August 2010

ABSTRACTNK cells are important innate immune effectors during influenza virus infection. However, the influenza virus seems able to use several tactics to counter NK cell recognition for immune evasion. In this review, we will summarize and discuss recent advances regarding the understanding of NK cell evasion mechanisms manipulated by the influenza virus to facilitate its rapid replication inside the respiratory epithelial cells.
Obesity Is a Fibroblast Growth Factor 21 (FGF21)-Resistant State
Authors: Fisher ffolliott M. , Chui Patricia C. , Antonellis Patrick J. , Bina Holly A. , Kharitonenkov Alexei , Flier Jeffrey S. , Maratos-Flier Eleftheria 
Published: August 2010

OBJECTIVE
Fibroblast growth factor 21 (FGF21) is a key mediator of fatty acid oxidation and lipid metabolism. Pharmacological doses of FGF21 improve glucose tolerance, lower serum free fatty acids, and lead to weight loss in obese mice. Surprisingly, however, FGF21 levels are elevated in obese ob/ob and db/db mice and correlate positively with BMI in humans. However, the expected beneficial effects of endogenous FGF21 to increase glucose tolerance and reduce circulating triglycerides are absent in obesity.

RESEARCH DESIGN AND METHODS
To test the hypothesis that obesity is a state of FGF21 resistance, we evaluated the response of obese mice to exogenous FGF21 administration. In doing this, we assessed the impact of diet-induced obesity on FGF21 signaling and resultant transcriptional events in the liver and white adipose tissue. We also analyzed the physiologic impact of FGF21 resistance by assessing serum parameters that are acutely regulated by FGF21.

RESULTS
When obese mice are treated with FGF21, they display both a significantly attenuated signaling response as assessed by extracellular mitogen-activated protein kinase 1 and 2 (ERK1/2) phosphorylation as well as an impaired induction of FGF21 target genes, including cFos and EGR1. These effects were seen in both liver and fat. Similarly, changes in serum parameters such as the decline in glucose and free fatty acids are attenuated in FGF21-treated DIO mice.

CONCLUSIONS
These data demonstrate that DIO mice have increased endogenous levels of FGF21 and respond poorly to exogenous FGF21. We therefore propose that obesity is an FGF21-resistant state.
Insulin Transactivator MafA Regulates Intrathymic Expression of Insulin and Affects Susceptibility to Type 1 Diabetes
Authors: Noso Shinsuke , Kataoka Kohsuke , Kawabata Yumiko , Babaya Naru , Hiromine Yoshihisa , Yamaji Kaori , Fujisawa Tomomi , Aramata Shinsaku , Kudo Takashi , Takahashi Satoru , Ikegami Hiroshi 
Published: August 2010

OBJECTIVE
Tissue-specific self-antigens are ectopically expressed within the thymus and play an important role in the induction of central tolerance. Insulin is expressed in both pancreatic islets and the thymus and is considered to be the primary antigen for type 1 diabetes. Here, we report the role of the insulin transactivator MafA in the expression of insulin in the thymus and susceptibility to type 1 diabetes.

RESEARCH DESIGN AND METHODS
The expression profiles of transcriptional factors (Pdx1, NeuroD, Mafa, and Aire) in pancreatic islets and the thymus were examined in nonobese diabetic (NOD) and control mice. Thymic Ins2 expression and serum autoantibodies were examined in Mafa knockout mice. Luciferase reporter assay was performed for newly identified polymorphisms of mouse Mafa and human MAFA. A case-control study was applied for human MAFA polymorphisms.

RESULTS
Mafa, Ins2, and Aire expression was detected in the thymus. Mafa expression was lower in NOD thymus than in the control and was correlated with Ins2 expression. Targeted disruption of MafA reduced thymic Ins2 expression and induced autoantibodies against pancreatic islets. Functional polymorphisms of MafA were newly identified in NOD mice and humans, and polymorphisms of human MAFA were associated with susceptibility to type 1 diabetes but not to autoimmune thyroid disease.

CONCLUSIONS
These data indicate that functional polymorphisms of MafA are associated with reduced expression of insulin in the thymus and susceptibility to type 1 diabetes in the NOD mouse as well as human type 1 diabetes.
Acute Pancreatitis in Type 2 Diabetes Treated With Exenatide or Sitagliptin
Authors: Garg Rajesh , Chen William , Pendergrass Merri 
Published: August 2010

OBJECTIVE
Cases of acute pancreatitis have been reported in association with exenatide, sitagliptin, and type 2 diabetes without use of these medications. It remains unknown whether exenatide or sitagliptin increase the risk of acute pancreatitis.

RESEARCH DESIGN AND METHODS
A retrospective cohort study of a large medical and pharmacy claims database was performed. Data for 786,656 patients were analyzed. Cox proportional hazard models were built to compare the risk of acute pancreatitis between diabetic and nondiabetic subjects and between exenatide, sitagliptin, and control diabetes medication use.

RESULTS
Incidence of acute pancreatitis in the nondiabetic control group, diabetic control group, exenatide group, and sitagliptin group was 1.9, 5.6, 5.7, and 5.6 cases per 1,000 patient years, respectively. The risk of acute pancreatitis was significantly higher in the combined diabetic groups than in the nondiabetic control group (adjusted hazard ratio 2.1 [95% CI 1.7–2.5]). Risk of acute pancreatitis was similar in the exenatide versus diabetic control group (0.9 [0.6–1.5]) and sitagliptin versus diabetic control group (1.0 [0.7–1.3]).

CONCLUSIONS
Our study demonstrated increased incidence of acute pancreatitis in diabetic versus nondiabetic patients but did not find an association between the use of exenatide or sitagliptin and acute pancreatitis. The limitations of this observational claims-based analysis cannot exclude the possibility of an increased risk.
Evaluation of Ankylosing Spondylitis Quality of Life (EASi-QoL): Reliability and Validity of a New Patient-reported Outcome Measure
Authors: HAYWOOD KIRSTIE L. , GARRATT ANDREW M. , JORDAN KELVIN P. , HEALEY EMMA L. , PACKHAM JONATHAN C. 
Published: August 2010

Objective.There is currently no universally accepted measure of quality of life in ankylosing spondylitis (AS). Our objective was to develop and evaluate a patient-reported outcome measure of quality of life in AS, EASi-QoL.Methods.We used patient interviews, a literature review, and completion of an individualized measure of AS quality of life during clinic-based and pilot surveys to derive questionnaire content. Classical and modern psychometrics were then used to evaluate the questionnaire using data from a large UK-based postal survey of 1000 patients with AS.Results.Data analysis from the interviews and clinic-based and postal surveys produced a 57-item self-completed questionnaire. Fifteen items were removed as a result of patient interviews and the pilot survey. In total, 612 (64.0%) patients responded to the main postal survey. After assessment of data quality, confirmatory factor analysis, and Rasch analysis, 20 items were found to contribute to 4 domains of AS-related quality of life: physical function, disease activity, emotional well-being, and social participation. Item-total correlations ranged from 0.66 to 0.84. Cronbach’s alpha and test-retest reliability estimates were 0.88–0.92 and 0.88–0.93, respectively. Confirmed hypothesized correlations with the AS Quality of Life questionnaire, the Bath AS Disease Activity Index, Bath AS Functional Index, SF-36, EQ-5D, and the Hospital Anxiety and Depression Scale were evidence for the construct validity of the EASi-QoL.Conclusion.The EASi-QoL has good evidence of data quality, internal reliability, test-retest reliability, and content and construct validity, and should be considered for use with patients in routine practice settings and in evaluative studies including clinical trials. Measurement responsiveness and minimal important change are currently being assessed.
Étude exploratoire des interfaces homme-machines éducatives pour l'autisme
Authors: Grynszpan Ouriel 
Published: August 2010

RÉSUMÉ La présente recherche consiste en une étude pilote pour prospecter les possibilités de l’éducation informatisée pour l’autisme. Elle s’appuie sur un protocole expérimental permettant d’étudier deux dimensions : le domaine d’apprentissage ciblé par les jeux éducatifs (la planification spatiale versus la compréhension de dialogues), et les modalités utilisées dans l’Interface Homme-Machine (IHM). Des jeux informatiques ont été développés puis testés avec des participants atteints d’autisme et des participants typiques. L’apprentissage était évalué par comparaison entre les performances avant et après une période d’entraînement. Les résultats ont permis de mettre en évidence le rôle joué par les fonctions exécutives dans l’activité informatique.
Des stratégies comportementales d'attachement aux stratégies représentationnelles : construction et validité des cartes de codage pour les histoires à compléter
Authors: Miljkovitch Raphaële , Pierrehumbert Blaise 
Published: August 2010

RÉSUMÉ L’article présente l’actualité d’un système de codage des histoires d’attachement à compléter (Bretherton & Ridgeway, 1990) sous forme du Q-sort, à l’usage de l’examinateur. Ce système permet de mesurer, dès l’âge de 3 ans, les stratégies représentationnelles d’attachement par des mesures de proximité avec 4 prototypes (sécurité, inhibition, hyperactivation et désorganisation du système d’attachement), de même que des caractéristiques de jeu et des contenus de représentations plus spécifiques à travers 7 échelles issues d’une analyse en composantes principales. Certaines de ces échelles varient en fonction de l’âge et du sexe, ce qui n’est pas le cas des stratégies d’attachement (à l’exception de la désorganisation, plus marquée chez les garçons). Les scores obtenus par le biais de ce codage ne sont pas influencés par le QI de l’enfant. La validité externe du Q-sort a été établie par des associations significatives avec les représentations de la mère d’après l’AAI, et avec des comportements interactifs avec la mère d’après le Care Index. Par ailleurs, une corrélation négative entre les représentations de soutien parental et des symptômes d’internalisation d’après le CBCL vient corroborer des résultats trouvés par d’autres auteurs.
Représentations d'attachement évaluées avec les histoires à compléter et troubles du comportement chez des enfants de 6 ans
Authors: Gloger-Tippel Gabriele , König Lilith , Lahl Olaf 
Published: August 2010

RÉSUMÉ Il a été montré que le lien d’attachement entre un enfant et son pourvoyeur de soins est un indicateur majeur de son adaptation socio-émotionnelle. À partir de l’âge préscolaire, l’attachement peut être mesuré au niveau représentationnel en utilisant la tâche des histoires d’attachement à compléter, codées à l’aide du « Düsseldorf Coding System » (DCS). Les résultats de l’étude longitudinale de Düsseldorf soutiennent l’hypothèse que les enfants avec un attachement sécurisé auront moins de troubles du comportement que les enfants avec un attachement insécurisé. 66 enfants de 5 ans ont été évalués deux à trois mois après leur entrée à l’école. Les mères évaluaient le comportement de leur enfant avec le « Social Behavior Questionnaire » et le « Child Behavior Checklist » ; les enseignants répondaient au « Teacher Report Form ». Du point de vue des troubles du comportement, les différences les plus importantes concernant les catégories d’attachement sont entre les types d’attachement désorganisé et sécurisé. L’appartenance à ces groupes compte pour 15 % et 10 % de la variance totale des troubles du comportement, selon qu’ils sont évalués par la mère ou par l’enseignant.