bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emodin targets the β-hydroxyacyl-acyl carrier protein dehydratase from Helicobacter pylori: enzymatic inhibition assay with crystal structural and thermodynamic characterization
Authors: Chen Jing , Zhang Liang , Zhang Yu , Zhang Haitao , Du Jiamu , Ding Jianping , Guo Yuewei , Jiang Hualiang , Shen Xu 
Published: May 2009

Abstract

Background
The natural product Emodin demonstrates a wide range of pharmacological properties including anticancer, anti-inflammatory, antiproliferation, vasorelaxant and anti-H. pylori activities. Although its H. pylori inhibition was discovered, no acting target information against Emodin has been revealed to date.

Results
Here we reported that Emodin functioned as a competitive inhibitor against the recombinant β-hydroxyacyl-ACP dehydratase from Helicobacter pylori (HpFabZ), and strongly inhibited the growth of H. pylori strains SS1 and ATCC 43504. Surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) based assays have suggested the kinetic and thermodynamic features of Emodin/HpFabZ interaction. Additionally, to inspect the binding characters of Emodin against HpFabZ at atomic level, the crystal structure of HpFabZ-Emodin complex was also examined. The results showed that Emodin inhibition against HpFabZ could be implemented either through its occupying the entrance of the tunnel or embedding into the tunnel to prevent the substrate from accessing the active site.

Conclusion
Our work is expected to provide useful information for illumination of Emodin inhibition mechanism against HpFabZ, while Emodin itself could be used as a potential lead compound for further anti-bacterial drug discovery.
Characterization of Vitis vinifera NPR1 homologs involved in the regulation of Pathogenesis-Related gene expression
Authors: Le Henanff Gaëlle , Heitz Thierry , Mestre Pere , Mutterer Jerôme , Walter Bernard , Chong Julie 
Published: May 2009

AbstractBackgroundGrapevine protection against diseases needs alternative strategies to the use of phytochemicals, implying a thorough knowledge of innate defense mechanisms. However, signalling pathways and regulatory elements leading to induction of defense responses have yet to be characterized in this species. In order to study defense response signalling to pathogens inVitis vinifera, we took advantage of its recently completed genome sequence to characterize two putative orthologs ofNPR1, a key player in salicylic acid (SA)-mediated resistance to biotrophic pathogens inArabidopsis thaliana.ResultsTwo cDNAs namedVvNPR1.1andVvNPR1.2were isolated fromVitis viniferacv Chardonnay, encoding proteins showing 55% and 40% identity to Arabidopsis NPR1 respectively. Constitutive expression ofVvNPR1.1andVvNPR1.2monitored in leaves ofV. viniferacv Chardonnay was found to be enhanced by treatment with benzothiadiazole, a SA analog. In contrast,VvNPR1.1andVvNPR1.2transcript levels were not affected during infection of resistantVitis ripariaor susceptibleV. viniferawithPlasmopara viticola, the causal agent of downy mildew, suggesting regulation of VvNPR1 activity at the protein level. VvNPR1.1-GFP and VvNPR1.2-GFP fusion proteins were transiently expressed by agroinfiltration inNicotiana benthamianaleaves, where they localized predominantly to the nucleus. In this system,VvNPR1.1andVvNPR1.2expression was sufficient to trigger the accumulation of acidic SA-dependent Pathogenesis-Related proteins PR1 and PR2, but not of basic chitinases (PR3) in the absence of pathogen infection. Interestingly, whenVvNPR1.1orAtNPR1were transiently overexpressed inVitis viniferaleaves, the induction of grapevinePR1was significantly enhanced in response toP. viticola.ConclusionIn conclusion, our data identified grapevine homologs of NPR1, and their functional analysis showed that VvNPR1.1 and VvNPR1.2 likely control the expression of SA-dependent defense genes. Overexpression ofVvNPR1has thus the potential to enhance grapevine defensive capabilities upon fungal infection. As a consequence, manipulatingVvNPR1and other signalling elements could open ways to strengthen disease resistance mechanisms in this crop species.
Therapeutic implications of selecting the SCORE (European) versus the D'AGOSTINO (American) risk charts for cardiovascular risk assessment in hypertensive patients
Authors: Gómez-Marcos Manuel A , Martínez-Salgado Carlos , Martin-Cantera Carlos , Recio-Rodríguez José I , Castaño-Sánchez Yolanda , Giné-Garriga Maria , Rodriguez-Sanchez Emiliano , García-Ortiz Luis 
Published: May 2009

Abstract

Background
No comparisons have been made of scales estimating cardiovascular mortality and overall cardiovascular morbidity and mortality. The study objectives were to assess the agreement between the Framingham-D'Agostino cardiovascular risk (CVR) scale and the chart currently recommended in Europe (SCORE) with regard to identification of patients with high CVR, and to describe the discrepancies between them and the attendant implications for the treatment of hypertension and hyperlipidaemia.

Methods
A total of 474 hypertensive patients aged 40–65 years monitored in primary care were enrolled into the study. CVR was assessed using the Framingham-D'Agostino scale, which estimates the overall cardiovascular morbidity and mortality risk, and the SCORE chart, which estimates the cardiovascular mortality risk. Cardiovascular risk was considered to be high for values ≥ 20% and ≥ 5% according to the Framingham-D'Agostino and SCORE charts respectively. Kappa statistics was estimated for agreement in classification of patients with high CVR. The therapeutic recommendations in the 2007 European Guidelines on Cardiovascular Disease Prevention were followed.

Results
Mean patient age was 54.1 (SD 7.3), and 58.4% were males. A high CVR was found in 17.5% using the SCORE chart (25.3% males, 6.6% females) and in 32.7% using the D'Agostino method (56.9% males, 12,7% females). Kappa coefficient was 0.52, and increased to 0.68 when the high CVR threshold was established at 29% according to D'Agostino. Hypertensive patients with high SCORE and non-high D'Agostino (1.7%) were characterized by an older age, diabetes, and a lower atherogenic index, while the opposite situation (16.9%) was associated to males, hyperlipidaemia, and a higher atherogenic index. Variables with a greater weight in discrepancies were sex and smoking. A 32.0% according to SCORE and 33.5% according to D'Agostino would be candidates to receive antihypertensive treatment, and 15.8% and 27.3% respectively to receive lipid-lowering treatment.

Conclusion
A moderate to high agreement was found. SCORE may underestimate risk in males with an unfavourable lipid profile, and D'Agostino in diabetics with a lower atherogenic risk. Use of the D'Agostino scale implies treating more patients with lipid-lowering and antihypertensive drugs as compared to SCORE.
Does the availability of positron emission tomography modify diagnostic strategies for solitary pulmonary nodules? An observational study in France
Authors: Lemonnier Irawati , Baumann Cédric , Jay Nicolas , Alzahouri Kazem , Arveux Patrick , Jolly Damien , Lejeune Catherine , Velten Michel , Vitry Fabien , Woronoff-Lemsi Marie-Christine , Guillemin Francis 
Published: May 2009

Abstract

Background
Previous studies showed that at the individual level, positron emission tomography (PET) has some benefits for patients and physicians in terms of cancer management and staging. We aimed to describe the benefits of (PET) in the management of solitary pulmonary nodules (SPNs) in a population level, in terms of the number of diagnostic and invasive tests performed, time to diagnosis and factors determining PET utilization.

Methods
In an observational study, we examined reports of computed tomography (CT) performed and mentioning "spherical lesion", "nodule" or synonymous terms. We found 11,515 reports in a before-PET period, 2002–2003, and 20,075 in an after-PET period, 2004–2005. Patients were followed through their physician, who was responsible for diagnostic management.

Results
We had complete data for 112 patients (73.7%) with new cases of SPN in the before-PET period and 250 (81.4%) in the after-PET period. Patients did not differ in mean age (64.9 vs. 64.8 years). The before-PET patients underwent a mean of 4 tests as compared with 3 tests for the after-PET patients (p = 0.08). Patients in the before-PET period had to wait 41.4 days, on average, before receiving a diagnosis as compared with 24.0 days, on average, for patients in the after-PET period who did not undergo PET (p < 0.001). In the after-PET period, 11% of patients underwent PET during the diagnostic process. A spiculated nodule was more likely to determine prescription for PET (p < 0.001). Multivariate analysis revealed that patients in both periods underwent fewer tests when PET was prescribed by general practitioners (p < 0.001) and if the nodule was not spiculated (p < 0.001). The proportion of unnecessary invasive approaches prescribed (47% vs. 49%) did not differ between the groups.

Conclusion
In our study, 1 year after the availability of PET, the technology was not the first choice for diagnostic management of SPN. Even though we observed a tendency for reduced number of tests and mean time to diagnosis with PET, these phenomena did not fully relate to PET availability in health communities. In addition, the availability of PET in the management of SPN diagnosis did not reduce the overall rate of unnecessary invasive approaches.
Trends in thyroid hormone prescribing and consumption in the UK
Authors: Mitchell Anna L , Hickey Bryan , Hickey Janis L , Pearce Simon HS 
Published: May 2009

AbstractBackgroundThyroid hormone replacement is one of the most commonly prescribed and cost effective treatments for a chronic disease. There have been recent changes in community prescribing policies in many areas of the UK that have changed patient access to necessary medications. This study aimed to provide a picture of thyroid hormone usage in the UK and to survey patient opinion about current community prescribing policies for levothyroxine.MethodsData on community prescriptions for thyroid hormones in England between 1998 and 2007, provided by the Department of Health, were collated and analysed. A survey of UK members of a patient support organisation (the British Thyroid Foundation) who were taking levothyroxine was carried out.ResultsThe amount of prescribed thyroid hormones used in England has more than doubled, from 7 to almost 19 million prescriptions, over the last 10 years. The duration of prescriptions has reduced from 60 to 45 days, on average over the same time. Two thousand five hundred and fifty one responses to the patient survey were received. Thirty eight percent of levothyroxine users reported receiving prescriptions of 28 days' duration. 59% of respondents reported being dissatisfied with 28-day prescribing.ConclusionAmongst users of levothyroxine, there is widespread patient dissatisfaction with 28-day prescription duration. Analysis of the full costs of 28-day dispensing balanced against the potential savings of reduced wastage of thyroid medications, suggests that this is unlikely to be an economically effective public health policy.
Multilevel analysis of HIV related risk behaviors among heroin users in a low prevalence community
Authors: Li Huizhen , Goggins William , Lee Shui Shan 
Published: May 2009

Abstract

Background
Injecting drug users (IDU) are at increased risk of human immunodeficiency virus (HIV) infection. Their HIV prevalence however varies from place to place and may not be directly linked with the level of individual risk. This study explores the relative importance of individual and community level characteristics in the practice of HIV-related risk behaviors in IDU in Hong Kong where the HIV prevalence has remained low at below 1%.

Methods
Methadone clinics were used as the channel for accessing drug users in Hong Kong. HIV-related risk factors in drug users attending these clinics were retrieved from a questionnaire routinely administered to newly admitted and readmitted clients, and assessed using logistic regression and multilevel analyses.

Results
Between 1999 and 2005, a total of 41196 person-admissions were recorded by 20 methadone clinics. Male gender, older age and new admissions in bigger clinics located in districts with older median age were more likely to have engaged in HIV related risk behaviors including heroin injection, needle sharing, unprotected sex and having multiple sex partners (p < 0.05).

Conclusion
Multilevel analysis is a useful adjunct for determining the association between risk behaviors and both individual and community factors in IDUs, which can be demonstrated even in low HIV prevalence settings.
Binding characteristics of the ovine membrane progesterone receptor alpha and expression of the receptor during the estrous cycle
Authors: Ashley Ryan L , Arreguin-Arevalo J Alejandro , Nett Terry M 
Published: May 2009

Abstract

Background
Classically, progesterone has been thought to act only through the well-known genomic pathway involving hormone binding to nuclear receptors and subsequent modulation of gene expression. However, there is increasing evidence for rapid, non-genomic effects of progesterone in a variety of mammalian tissues and it is possible that a membrane PR (mPR) is causing these events. We recently isolated and characterized an ovine mPR referred to as mPR-alpha, distinct from the nuclear PR. Based on predicted structural analysis, the ovine mPR-alpha possesses seven transmembrane domains typical of G protein-coupled receptors. Despite the homology to other reported mPRs, information pertaining to the steroid binding characteristics of the ovine mPR-alpha was lacking. Additionally, the ovine mPR-alpha transcript has been identified in the hypothalamus, pituitary, uterus, ovary and corpus luteum, yet changes in expression of the ovine mPR-alpha in these tissues were not known. Consequently, the purpose of this work was to determine the steroid binding characteristics of the ovine mPR-alpha and to investigate possible changes in expression of the ovine mPR-alpha in reproductive tissues throughout the estrous cycle.

Methods
Binding studies were performed using crude membrane fractions from CHO cells expressing the mPR-alpha. Using quantitative Real-time PCR we determined the expression pattern of mRNA for the ovine mPR-alpha during the ovine estrous cycle in tissues known to express the mPR-alpha. Jugular blood samples were also collected and analyzed for serum concentrations of P4 to ensure ewes were at the appropriate stage of their cycle.

Results
Only progesterone, 20alpha-hydroxyprogesterone and 17alpha-hydroxyprogesterone were able to displace binding of 3H-P4 (P < 0.001) to membrane fractions from CHO cells expressing ovine mPR-alpha. The average B-max and Kd values for three separate experiments were 624 +/- 119 fmol/micro gram protein and 122 +/- 50 nM, respectively. Significant changes in expression of mRNA for the mPR-alpha during the estrous cycle were noted in the corpus luteum and uterus.

Conclusion
The mPR-alpha specifically binds progestins and its expression was correlated to progesterone secretion during the ovine estrous cycle. Results from the present studies suggest that mPR-alpha may have an important physiological role during the ovine estrous cycle.
Reduced expression of CRH receptor type 1 in upper segment human myometrium during labour
Authors: Cong Binhai , Zhang Lanmei , Gao Lu , Ni Xin 
Published: May 2009

Abstract

Background
Corticotropin-releasing hormone (CRH) and CRH-related peptide are shown to modulate uterine contractility through two CRH receptor subtype, CRH-R1 and CRH-R2 during pregnancy. Through different signaling pathways, CRH-R1 maintains myometrial quiescence whereas CRH-R2 promotes smooth muscle contractility. We hypothesized that the expression of CRH receptors in myometrium might be changed during pregnancy and labour.

Method
Immunohistochemistry, Western blot and RT-PCR were used to quantify the cellular localization, the protein levels and the mRNA variants of both CRH-R1 and CRH-R2 in upper segment (US) and lower segment (LS) myometrium from nonpregnant and pregnant women at term before or after labour.

Results
CRH-R1 and CRH-R2 were predominately localized to myometrial smooth muscle cells in US and LS. The protein level of CRH-R1 in US was significantly down-regulated in pregnancy, with a further decrease at the onset of labour. However, the expression of CRH-R1 in LS remained unchanged during pregnancy and labour. No significant changes in CRH-R2 expression were observed in US or LS. Six variants of CRH-R1, CRH-R1alpha,-R1beta,-R1c, -R1e,-R1f and -R1g, were identified in nonpregnant and pregnant myometrium. CRH-R2alpha was identified in pregnant myometrium, whereas CRH-R2beta was identified in nonpregnant myometrium

Conclusion
CRH-R1 and CRH-R2 are expressed in nonpregnant and pregnant US and LS myometrium. Changed expression of CRH receptors during labour may underlie the initiation of uterine contractility during parturition.
Single molecule resolution of the antimicrobial action of quantum dot-labeled sushi peptide on live bacteria
Authors: Leptihn Sebastian , Har Jia Yi , Chen Jianzhu , Ho Bow , Wohland Thorsten , Ding Jeak Ling 
Published: May 2009

Abstract

Background

Antimicrobial peptides are found in all kingdoms of life. During the evolution of multicellular organisms, antimicrobial peptides were established as key elements of innate immunity. Most antimicrobial peptides are thought to work by disrupting the integrity of cell membranes, causing pathogen death. As antimicrobial peptides target the membrane structure, pathogens can only acquire resistance by a fundamental change in membrane composition. Hence, the evolution of pathogen resistance has been a slow process. Therefore antimicrobial peptides are valuable alternatives to classical antibiotics against which multiple drug-resistant bacteria have emerged. For potential therapeutic applications as antibiotics a thorough knowledge of their mechanism of action is essential. Despite the increasingly comprehensive understanding of the biochemical properties of these peptides, the actual mechanism by which antimicrobial peptides lyse microbes is controversial.

Results

Here we investigate how Sushi 1, an antimicrobial peptide derived from the horseshoe crab (Carcinoscorpius rotundicauda), induces lysis of Gram-negative bacteria. To follow the entire process of antimicrobial action, we performed a variety of experiments including transmission electron microscopy and fluorescence correlation spectroscopy as well as single molecule tracking of quantum dot-labeled antimicrobial peptides on live bacteria. Since in vitro measurements do not necessarily correlate with the in vivo action of a peptide we developed a novel fluorescent live bacteria lysis assay. Using fully functional nanoparticle-labeled Sushi 1, we observed the process of antimicrobial action at the single-molecule level.

Conclusion

Recently the hypothesis that many antimicrobial peptides act on internal targets to kill the bacterium has been discussed. Here, we demonstrate that the target sites of Sushi 1 are outer and inner membranes and are not cytosolic. Further, our findings suggest four successive steps of the bactericidal process: 1) Binding, mediated mainly by charged residues in the peptide; 2) Peptide association, as peptide concentration increases evidenced by a change in diffusive behavior; 3) Membrane disruption, during which lipopolysaccharide is not released; and 4) Lysis, by leakage of cytosolic content through large membrane defects.
Can we apply the Mendelian randomization methodology without considering epigenetic effects?
Authors: Ogbuanu Ikechukwu U , Zhang Hongmei , Karmaus Wilfried 
Published: May 2009

Abstract
Introduction
Instrumental variable (IV) methods have been used in econometrics for several decades now, but have only recently been introduced into the epidemiologic research frameworks. Similarly, Mendelian randomization studies, which use the IV methodology for analysis and inference in epidemiology, were introduced into the epidemiologist's toolbox only in the last decade.

Analysis
Mendelian randomization studies using instrumental variables (IVs) have the potential to avoid some of the limitations of observational epidemiology (confounding, reverse causality, regression dilution bias) for making causal inferences. Certain limitations of randomized controlled trials, such as problems with generalizability, feasibility and ethics for some exposures, and high costs, also make the use of Mendelian randomization in observational studies attractive. Unlike conventional randomized controlled trials (RCTs), Mendelian randomization studies can be conducted in a representative sample without imposing any exclusion criteria or requiring volunteers to be amenable to random treatment allocation.
Within the last decade, epigenetics has gained recognition as an independent field of study, and appears to be the new direction for future research into the genetics of complex diseases. Although previous articles have addressed some of the limitations of Mendelian randomization (such as the lack of suitable genetic variants, unreliable associations, population stratification, linkage disequilibrium (LD), pleiotropy, developmental canalization, the need for large sample sizes and some potential problems with binary outcomes), none has directly characterized the impact of epigenetics on Mendelian randomization. The possibility of epigenetic effects (non-Mendelian, heritable changes in gene expression not accompanied by alterations in DNA sequence) could alter the core instrumental variable assumptions of Mendelian randomization.
This paper applies conceptual considerations, algebraic derivations and data simulations to question the appropriateness of Mendelian randomization methods when epigenetic modifications are present.

Conclusion
Given an inheritance of gene expression from parents, Mendelian randomization studies not only need to assume a random distribution of alleles in the offspring, but also a random distribution of epigenetic changes (e.g. gene expression) at conception, in order for the core assumptions of the Mendelian randomization methodology to remain valid. As an increasing number of epidemiologists employ Mendelian randomization methods in their research, caution is therefore needed in drawing conclusions from these studies if these assumptions are not met.