bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enzyme phylogenies as markers for the oxidation state of the environment: The case of respiratory arsenate reductase and related enzymes
Authors: Duval Simon , Ducluzeau Anne-Lise , Nitschke Wolfgang , Schoepp-Cothenet Barbara 
Published: July 2008

Abstract

Background
Phylogenies of certain bioenergetic enzymes have proved to be useful tools for deducing evolutionary ancestry of bioenergetic pathways and their relationship to geochemical parameters of the environment. Our previous phylogenetic analysis of arsenite oxidase, the molybdopterin enzyme responsible for the biological oxidation of arsenite to arsenate, indicated its probable emergence prior to the Archaea/Bacteria split more than 3 billion years ago, in line with the geochemical fact that arsenite was present in biological habitats on the early Earth. Respiratory arsenate reductase (Arr), another molybdopterin enzyme involved in microbial arsenic metabolism, serves as terminal oxidase, and is thus situated at the opposite end of bioenergetic electron transfer chains as compared to arsenite oxidase. The evolutionary history of the Arr-enzyme has not been studied in detail so far.

Results
We performed a genomic search of genes related to arrA coding for the molybdopterin subunit. The multiple alignment of the retrieved sequences served to reconstruct a neighbor-joining phylogeny of Arr and closely related enzymes. Our analysis confirmed the previously proposed proximity of Arr to the cluster of polysulfide/thiosulfate reductases but also unravels a hitherto unrecognized clade even more closely related to Arr. The obtained phylogeny strongly suggests that Arr originated after the Bacteria/Archaea divergence in the domain Bacteria, and was subsequently laterally distributed within this domain. It further more indicates that, as a result of accumulation of arsenate in the environment, an enzyme related to polysulfide reductase and not to arsenite oxidase has evolved into Arr.

Conclusion
These findings are paleogeochemically rationalized by the fact that the accumulation of arsenate over arsenite required the increase in oxidation state of the environment brought about by oxygenic photosynthesis.
The complete mitochondrial genome of the bag-shelter moth Ochrogaster lunifer (Lepidoptera, Notodontidae)
Authors: Salvato Paola , Simonato Mauro , Battisti Andrea , Negrisolo Enrico 
Published: July 2008

Abstract

Background
Knowledge of animal mitochondrial genomes is very important to understand their molecular evolution as well as for phylogenetic and population genetic studies. The Lepidoptera encompasses more than 160,000 described species and is one of the largest insect orders. To date only nine lepidopteran mitochondrial DNAs have been fully and two others partly sequenced. Furthermore the taxon sampling is very scant. Thus advance of lepidopteran mitogenomics deeply requires new genomes derived from a broad taxon sampling. In present work we describe the mitochondrial genome of the moth Ochrogaster lunifer.

Results
The mitochondrial genome of O. lunifer is a circular molecule 15593 bp long. It includes the entire set of 37 genes usually present in animal mitochondrial genomes. It contains also 7 intergenic spacers. The gene order of the newly sequenced genome is that typical for Lepidoptera and differs from the insect ancestral type for the placement of trnM. The 77.84% A+T content of its α strand is the lowest among known lepidopteran genomes. The mitochondrial genome of O. lunifer exhibits one of the most marked C-skew among available insect Pterygota genomes. The protein-coding genes have typical mitochondrial start codons except for cox1 that present an unusual CGA. The O. lunifer genome exhibits the less biased synonymous codon usage among lepidopterans. Comparative genomics analysis study identified atp6, cox1, cox2 as cox3, cob, nad1, nad2, nad4, and nad5 as potential markers for population genetics/phylogenetics studies. A peculiar feature of O. lunifer mitochondrial genome it that the intergenic spacers are mostly made by repetitive sequences.

Conclusion
The mitochondrial genome of O. lunifer is the first representative of superfamily Noctuoidea that account for about 40% of all described Lepidoptera. New genome shares many features with other known lepidopteran genomes. It differs however for its low A+T content and marked C-skew. Compared to other lepidopteran genomes it is less biased in synonymous codon usage. Comparative evolutionary analysis of lepidopteran mitochondrial genomes allowed the identification of previously neglected coding genes as potential phylogenetic markers. Presence of repetitive elements in intergenic spacers of O. lunifer genome supports the role of DNA slippage as possible mechanism to produce spacers during replication.
ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages
Authors: Biswas Debasis , Qureshi Omar S , Lee Wing-Yiu , Croudace Joanne E , Mura Manuela , Lammas David A 
Published: July 2008

Abstract

Background
We have previously reported that ATP treatment of M bovis-BCG infected human macrophages induces P2X7 receptor-dependent killing of intracellular mycobacteria. The mechanism mediating this bactericidal effect has not been full characterized but is known to be Ca2+-dependent and to promote the maturation and acidification of mycobacteria-containing phagosomes. In this study we demonstrate that the ATP/P2X7-mediated, mycobactericidal effect also involves the induction of cell autophagy.

Results
We report that 3 mM ATP induces rapid cell autophagy in THP1 cells and monocyte-derived macrophages within 30 minutes post-treatment, as revealed by the expression of LC3-II bands on western blot analysis. Using Ca2+-free media and selective P2X7 agonists and antagonists, ATP-induced cell autophagy was shown to be Ca2+ and P2X7 receptor-dependent. Electron microscopy of ATP-treated, BCG-infected MDMs revealed the presence of the bacteria within characteristic double-membraned autophagosomes. Confocal analysis further confirmed that pharmacological inhibition of autophagy by wortmannin or pre-treatment of macrophages with anti-P2X7 antibody blocked ATP-induced phago-lysosomal fusion. Induction of cell autophagy with ATP was also temporally associated with a fall in intracellular mycobacterial viability, which was suppressed by treatment with wortmannin or the selective P2X7 antagonist, oxidized ATP (oATP).

Conclusion
We provide the first evidence that ATP/P2X7-mediated killing of intracellular mycobacteria involves the induction of cell autophagy. The findings support the hypothesis that autophagy plays a key role in the control of mycobacterial infections.
Leukotriene B4-loaded microspheres: a new therapeutic strategy to modulate cell activation
Authors: Nicolete Roberto , Rius Cristina , Piqueras Laura , Jose Peter J , Sorgi Carlos A , Soares Edson G , Sanz Maria J , Faccioli Lúcia H 
Published: July 2008

AbstractBackgroundLeukotriene B4(LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4released from microspheres (MS). A previous oil-in-water emulsion solvent extraction-evaporation method was chosen to prepare LTB4-loaded MS.ResultsIn the mice cremasteric microcirculation, intraescrotal injection of 0.1 ml of LTB4-loaded MS provoked significant increases in leukocyte rolling flux, adhesion and emigration besides significant decreases in the leukocyte rolling velocity. LTB4-loaded MS also increase peroxisome proliferator-activated receptor-α (PPARα) expression by murine peritoneal macrophages and stimulate them to generate nitrite levels. Monocyte chemoattractant protein-1 (MCP-1) and nitric oxide (NO) productions were also increased when human umbilical vein and artery endothelial cells (HUVECs and HUAECs, respectively) were stimulated with LTB4-loaded MS.ConclusionLTB4-loaded MS preserve the biological activity of the encapsulated mediator indicating their use as a new strategy to modulate cell activation, especially in the innate immune response.
The function of BCL9 in Wnt/β-catenin signaling and colorectal cancer cells
Authors: de la Roche Marc , Worm Jesper , Bienz Mariann 
Published: July 2008

AbstractBackgroundMost cases of colorectal cancer are initiated by hyperactivation of the Wnt/β-catenin pathway due to mutations in the APC tumour suppressor, or in β-catenin itself. A recently discovered component of this pathway is Legless, which is essential for Wnt-induced transcription duringDrosophiladevelopment. Limited functional information is available for its two mammalian relatives, BCL9 and B9L/BCL9-2: like Legless, these proteins bind to β-catenin, and RNAi-mediated depletion of B9L/BCL9-2 has revealed that this protein is required for efficient β-catenin-mediated transcription in mammalian cell lines. No loss-of-function data are available for BCL9.MethodsWe have used overexpression of dominant-negative forms of BCL9, and RNAi-mediated depletion, to study its function in human cell lines with elevated Wnt pathway activity, including colorectal cancer cells.ResultsWe found that BCL9 is required for efficient β-catenin-mediated transcription in Wnt-stimulated HEK 293 cells, and in the SW480 colorectal cancer cell line whose Wnt pathway is active due toAPCmutation. Dominant-negative mutants of BCL9 indicated that its function depends not only on its β-catenin ligand, but also on an unknown ligand of its C-terminus. Finally, we show thatBCL9andB9Lare both Wnt-inducible genes, hyperexpressed in colorectal cancer cell lines, indicating that they are part of a positive feedback loop.ConclusionBCL9 is required for efficient β-catenin-mediated transcription in human cell lines whose Wnt pathway is active, including colorectal cancer cells, indicating its potential as a drug target in colorectal cancer.
Modelling lifetime cost consequences of ReSTOR®in cataract surgery in four European countries
Authors: Lafuma Antoine , Berdeaux Gilles 
Published: July 2008

Abstract

Background
To compare the lifetime costs of liberating patients from spectacles after cataract surgery by implanting the multifocal intraocular lens (IOL) 'ReSTOR®' versus monofocal IOLs in France, Italy, Germany and Spain.

Methods
A Markov model was created to follow patient cohorts from cataract surgery until death. Prevalence rates of patients not needing spectacles after cataract surgery were obtained from clinical trials. Resource utilisation included implant surgery, IOLs, spectacles, visits to ophthalmologists and eye centres, transport, and time lost by patients. Economic perspectives were those of Society and Sickness Funds (SFs).

Results
The mean number of spectacles purchased after ReSTOR® was 1.34–1.61 and after monofocal IOLs 6.05–7.27. From the societal perspective, total cost estimates discounted by 3% were between €3,551 and €4,052 with ReSTOR® compared to €3,989 and €5,548 with monofocal IOLs. Undiscounted savings related to ReSTOR® ranged from €815 to €2,164. From the SFs' perspective total cost estimates discounted by 3% were between €2,150 and €2,524 with ReSTOR® compared to €2,324 and €2,610 with monofocal IOLs. Savings related to ReSTOR®, once costs discounted, ranged from €61 to €219. Discount and spectacle freedom prevalence rates were the most sensitive parameters.

Conclusion
The bulk of the savings related to ReSTOR® were realized outside the SF. From both a societal and SF perspective, savings, after a 3% discounting, achieved by liberating patients from spectacles counterbalanced the initially higher cost of ReSTOR®. ReSTOR® is a cost saving alternative to spectacles for patients requiring cataract surgery.
Delayed Treatment of Diagnosed Pulmonary Tuberculosis in Taiwan
Authors: Chern Jimmy PS , Chen Duan-Rung , Wen Tzai-Hung 
Published: July 2008

Abstract

Background
Mycobacterium tuberculosis infection is an ongoing public health problem in Taiwan. The National Tuberculosis Registry Campaign, a case management system, was implemented in 1997. This study examined this monitoring system to identify and characterize delayed treatment of TB patients.

Methods
Records of all tuberculosis cases treated in Taiwan from 2002 through 2005 were obtained from the National Tuberculosis Registry Campaign. Initiation of treatment more than 7 days after diagnosis was considered a long treatment delay.

Results
The study included 31,937 patients. The mean day of delayed treatment was 3.6 days. Most patients were treated immediately after diagnosis. The relationship between number of TB patients and days of delayed treatment after diagnosis exhibited a Power-law distribution. The long tail of the power-law distribution indicated that an extreme number occur cannot be neglected. Tuberculosis patients treated after an unusually long delay require close observation and follow up.

Conclusion
This study found that TB control is generally acceptabl in Taiwan; however, delayed treatment increases the risk of transmission. Improving the protocol for managing confirmed TB cases can minimize disease transmission.
Analysis of transient phosphorylation-dependent protein-protein interactions in living mammalian cells using split-TEV
Authors: Wehr Michael C , Reinecke Lisa , Botvinnik Anna , Rossner Moritz J 
Published: July 2008

AbstractBackgroundRegulated protein-protein interactions (PPIs) are pivotal molecular switches that are important for the regulation of signaling processes within eukaryotic cells. Cellular signaling is altered in various disease conditions and offers interesting options for pharmacological interventions. Constitutive PPIs are usually mediated by large interaction domains. In contrast, stimulus-regulated PPIs often depend on small post-translational modifications and are thus better suited targets for drug development. However, the detection of modification-dependent PPIs with biochemical methods still remains a labour- and material-intensive task, and many pivotal PPIs that are potentially suited for pharmacological intervention most likely remain to be identified. The availability of methods to easily identify and quantify stimulus-dependent, potentially also transient interaction events, is therefore essential. The assays should be applicable to intact mammalian cells, optimally also to primary cells in culture.ResultsIn this study, we adapted the split-TEV system to quantify phosphorylation-dependent and transient PPIs that occur at the membrane and in the cytosol of living mammalian cells. Split-TEV is based on a PPI-induced functional complementation of two inactive TEV protease fragments fused to interaction partners of choice. Genetically encoded transcription-coupled and proteolysis-only TEV reporter systems were used to convert the TEV activity into an easily quantifiable readout. We measured the phosphorylation-dependent interaction between the pro-apoptotic protein Bad and the adapter proteins 14-3-3ε and ζ in NIH-3T3 fibroblasts and in primary cultured neurons. Using split-TEV assays, we show that Bad specifically interacts with 14-3-3 isoforms when phosphorylated by protein kinase Akt-1/PKB at Ser136. We also measured the phosphorylation-dependent Bad/14-3-3 interactions mediated by endogenous and transient Akt-1 activity. We furthermore applied split-TEV assays to measure the phosphorylation-dependent interactions of Neuregulin-1-stimulated ErbB4 receptors with several adapter proteins.ConclusionSplit-TEV assays are well suited to measure phosphorylation-dependent and transient PPIs that occur specifically at the membrane and in the cytosol of heterologous and primary cultured mammalian cells. Given the high sensitivity of the split-TEV system, all assays were performed in multi-plate formats and could be adapted for higher throughput to screen for pharmacologically active substances.
Evaluation of light microscopy and rapid diagnostic test for the detection of malaria under operational field conditions: a household survey in Ethiopia
Authors: Endeshaw Tekola , Gebre Teshome , Ngondi Jeremiah , Graves Patricia M , Shargie Estifanos B , Ejigsemahu Yeshewamebrat , Ayele Berhan , Yohannes Gedeon , Teferi Tesfaye , Messele Ayenew , Zerihun Mulat , Genet Asrat , Mosher Aryc W , Emerson Paul M , Richards Frank O 
Published: July 2008

Abstract

Background
In most resource-poor settings, malaria is usually diagnosed based on clinical signs and symptoms and not by detection of parasites in the blood using microscopy or rapid diagnostic tests (RDT). In population-based malaria surveys, accurate diagnosis is important: microscopy provides the gold standard, whilst RDTs allow immediate findings and treatment. The concordance between RDTs and microscopy in low or unstable transmission areas has not been evaluated.

Objectives
This study aimed to estimate the prevalence of malaria parasites in randomly selected malarious areas of Amhara, Oromia, and Southern Nations, Nationalities and Peoples' (SNNP) regions of Ethiopia, using microscopy and RDT, and to investigate the agreement between microscopy and RDT under field conditions.

Methods
A population-based survey was conducted in 224 randomly selected clusters of 25 households each in Amhara, Oromia and SNNP regions, between December 2006 and February 2007. Fingerpick blood samples from all persons living in even-numbered households were tested using two methods: light microscopy of Giemsa-stained blood slides; and RDT (ParaScreen device for Pan/Pf).

Results
A total of 13,960 people were eligible for malaria parasite testing of whom 11,504 (82%) were included in the analysis. Overall slide positivity rate was 4.1% (95% confidence interval [CI] 3.4–5.0%) while ParaScreen RDT was positive in 3.3% (95% CI 2.6–4.1%) of those tested. Considering microscopy as the gold standard, ParaScreen RDT exhibited high specificity (98.5%; 95% CI 98.3–98.7) and moderate sensitivity (47.5%; 95% CI 42.8–52.2) with a positive predictive value of 56.8% (95% CI 51.7–61.9) and negative predictive value of 97.6% (95% CI 97.6–98.1%) under field conditions.

Conclusion
Blood slide microscopy remains the preferred option for population-based prevalence surveys of malaria parasitaemia. The level of agreement between microscopy and RDT warrants further investigation in different transmission settings and in the clinical situation.
Performance of self-diagnosis and standby treatment of malaria in international oilfield service employees in the field
Authors: Roukens Anna H , Berg Johannes , Barbey Alex , Visser Leo G 
Published: July 2008

Abstract

Background
Falciparum malaria remains a major occupational illness that accounts for several deaths per year and numerous lost working days among the expatriate population, working or living in high-risk malarious areas. Compliance to preventive strategies is poor in travellers, especially business travellers, expatriates and long-term travellers.

Methods
In this cross-sectional, web-based study the adherence to and outcome of a preventive malaria programme on knowledge, attitudes and practices, including the practice of self-diagnosis and standby treatment (curative malaria kit, CMK) was evaluated in 2,350 non-immune expatriates, who had been working in highly malaria endemic areas.

Results
One-third (N = 648) of these expatriates visited a doctor for malaria symptoms and almost half (29 of 68) of all hospitalizations were due to malaria. The mandatory malaria training for non-immunes was completed by 92% of those who visited or worked in a high risk malaria country; 70% of the respondents at risk also received the CMK. The malaria awareness training and CMK significantly increased malaria knowledge [relative risk (RR) of 1.5, 95%CI 1.2–2.1], attitudes and practices, including compliance to chemoprophylaxis [RR = 2.2, 95%CI 1.6–3.2]. Hospitalization for malaria tended to be reduced by the programme [RR = 0.4, 95%CI 0.1–1.1], albeit not significantly. Respondents who did not receive instructions on the rapid diagnostic test were two times [RR = 2.3, 95%CI 1.6–3.3] more likely to have difficulties. Those who did receive instructions adhered poorly to the timing of repeating the test. Moreover, 6% (31 of 513) of those with a negative test result were diagnosed with malaria by a local doctor. 77% (N = 393) of the respondents with a negative test result did not take curative medication. 57% (252 of 441) of the respondents who took the curative medication that was included in the kit did not have a positive self-test or clinical malaria diagnosis made by a doctor.

Conclusion
This survey demonstrated that a comprehensive programme targeting malaria prevention in expatriates can be effectively implemented and that it significantly increased malaria awareness.
Correlates of preclinical cardiovascular disease in Indigenous and Non-Indigenous Australians: a case control study
Authors: Haluska Brian A , Chan Lionel , Jeffriess Leanne , Shaw A Andrew , Shaw Joanne , Marwick Thomas H 
Published: July 2008

Abstract

Background
The high frequency of premature death from cardiovascular disease in indigenous Australians is often attributed to the high prevalence of risk factors, especially type II diabetes mellitus (DM). We evaluated the relationship of ethnicity to atherosclerotic burden, as evidenced by carotid intima-media thickness (IMT), independent of risk factor status.

Methods
We studied 227 subjects (147 men; 50 ± 13 y): 119 indigenous subjects with (IDM, n = 54), and without DM (InDM, n = 65), 108 Caucasian subjects with (CDM, n = 52), and without DM (CnDM, n = 56). IMT was measured according to standard methods and compared with clinical data and cardiovascular risk factors.

Results
In subjects both with and without DM, IMT was significantly greater in indigenous subjects. There were no significant differences in gender, body mass index (BMI), systolic blood pressure (SBP), or diastolic blood pressure (DBP) between any of the groups, and subjects with DM showed no difference in plasma HbA1c. Cardiovascular risk factors were significantly more prevalent in indigenous subjects. Nonetheless, ethnicity (β = -0.34; p < 0.0001), age (β = 0.48; p < 0.0001), and smoking (β = 0.13; p < 0.007) were independent predictors of IMT in multiple linear regression models.

Conclusion
Ethnicity appears to be an independent correlate of preclinical cardiovascular disease, even after correction for the high prevalence of cardiovascular risk factors in indigenous Australians. Standard approaches to control currently known risk factors are vital to reduce the burden of cardiovascular disease, but in themselves may be insufficient to fully address the high prevalence in this population.