bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione mediated regulation of oligomeric structure and functional activity of Plasmodium falciparum glutathione S-transferase
Authors: Tripathi Timir , Rahlfs Stefan , Becker Katja , Bhakuni Vinod 
Published: October 2007

AbstractBackgroundIn contrast to many other organisms, the malarial parasitePlasmodium falciparumpossesses only one typical glutathioneS-transferase. This enzyme,PfGST, cannot be assigned to any of the known GST classes and represents a most interesting target for antimalarial drug development. ThePfGST under native conditions forms non-covalently linked higher aggregates with major population (~98%) being tetramer. However, in the presence of 2 mM GSH, a dimer ofPfGST is observed. Recently reported study on binding and catalytic properties ofPfGST indicated a GSH dependent low-high affinity transition with simultaneous binding of two GSH molecules toPfGST dimer suggesting that GSH binds to low affinity inactive enzyme dimer converting it to high affinity functionally active dimer. In order to understand the role of GSH in tetramer-dimer transition ofPfGST as well as in modulation of functional activity of the enzyme, detailed structural, functional and stability studies on recombinantPfGST in the presence and absence of GSH were carried out.ResultsOur data indicate that the dimer – and not the tetramer – is the active form ofPfGST, and that substrate saturation is directly paralleled by dissociation of the tetramer. Furthermore, this dissociation is a reversible process indicating that the tetramer-dimer equilibrium ofPfGST is defined by the surrounding GSH concentration. Equilibrium denaturation studies show that thePfGST tetramer has significantly higher stability compared to the dimer. The enhanced stability of the tetramer is likely to be due to stronger ionic interactions existing in it.ConclusionThis is the first report for any GST where an alteration in oligomeric structure and not just small conformational change is observed upon GSH binding to the enzyme. Furthermore we also demonstrate a reversible mechanism of regulation of functional activity ofPlasmodium falciparumglutathioneS-transferase via GSH induced dissociation of functionally inactive tetramer into active dimers.
Online detection and quantification of epidemics
Authors: Pelat Camille , Boëlle Pierre-Yves , Cowling Benjamin J , Carrat Fabrice , Flahault Antoine , Ansart Séverine , Valleron Alain-Jacques 
Published: October 2007

AbstractBackgroundTime series data are increasingly available in health care, especially for the purpose of disease surveillance. The analysis of such data has long used periodic regression models to detect outbreaks and estimate epidemic burdens. However, implementation of the method may be difficult due to lack of statistical expertise. No dedicated tool is available to perform and guide analyses.ResultsWe developed an online computer application allowing analysis of epidemiologic time series. The system is available online athttp://www.u707.jussieu.fr/periodic_regression/. The data is assumed to consist of a periodic baseline level and irregularly occurring epidemics. The program allows estimating the periodic baseline level and associated upper forecast limit. The latter defines a threshold for epidemic detection. The burden of an epidemic is defined as the cumulated signal in excess of the baseline estimate. The user is guided through the necessary choices for analysis. We illustrate the usage of the online epidemic analysis tool with two examples: the retrospective detection and quantification of excess pneumonia and influenza (P&I) mortality, and the prospective surveillance of gastrointestinal disease (diarrhoea).ConclusionThe online application allows easy detection of special events in an epidemiologic time series and quantification of excess mortality/morbidity as a change from baseline. It should be a valuable tool for field and public health practitioners.
Evaluating compulsory minimum volume standards in Germany: how many hospitals were compliant in 2004?
Authors: de Cruppé Werner , Ohmann Christian , Blum Karl , Geraedts Max 
Published: October 2007

Abstract
Background
Minimum hospital procedure volumes are discussed as an instrument for quality assurance. In 2004 Germany introduced such annual minimum volumes nationwide on five surgical procedures: kidney, liver, stem cell transplantation, complex oesophageal, and pancreatic interventions. The present investigation is the first part of a study evaluating the effects of these minimum volumes on health care provision. Research questions address how many hospitals and cases were affected by minimum volume regulations in 2004, how affected hospitals were distributed according to minimum volumes, and how many hospitals within the 16 German states complied with the standards set for 2004.

Methods
The evaluation is based on the mandatory hospital quality reports for 2004. In the reports, all hospitals are statutorily obliged to state the number of procedures performed for each minimum volume. The data were analyzed descriptively.

Results
In 2004, 485 out of 1710 German hospitals providing acute care and approximately 0.14% of all hospital cases were affected by minimum volume regulations. Liver, kidney, and stem cell transplantation affected from 23 to hospitals; complex oesophageal and pancreatic interventions affected from 297 to 455 hospitals. The inter-state comparison of the average hospital care area demonstrates large differences between city states and large area states and the eastern and western German states ranging from a minimum 51 km2 up to a maximum 23.200 km2, varying according to each procedure. A range of 9% – 16% of the transplantation hospitals did not comply with the standards affecting 1% – 2% of the patients whereas 29% and 18% of the hospitals treating complex oesophageal and pancreatic interventions failed the standards affecting 2% – 5% of the prevailing cases.

Conclusion
In 2004, the newly introduced minimum volume regulations affected only up to a quarter of German acute care hospitals and few cases. However, excluding the hospitals not meeting the minimum volume standards from providing the respective procedures deserves considering two aspects: the hospital health care provision concepts by the German states as being responsible and from a patient perspective the geographically equal access to hospital care.
Do the UK government's new Quality and Outcomes Framework (QOF) scores adequately measure primary care performance? A cross-sectional survey of routine healthcare data
Authors: Downing Amy , Rudge Gavin , Cheng Yaping , Tu Yu-Kang , Keen Justin , Gilthorpe Mark S 
Published: October 2007

Abstract
Background
General practitioners' remuneration is now linked directly to the scores attained in the Quality and Outcomes Framework (QOF). The success of this approach depends in part on designing a robust and clinically meaningful set of indicators. The aim of this study was to assess the extent to which measures of health observed in practice populations are correlated with their QOF scores, after accounting for the established associations between health outcomes and socio-demographics.

Methods
QOF data for the period April 2004 to March 2005 were obtained for all general practices in two English Primary Care Trusts. These data were linked to data for emergency hospital admissions (for asthma, cancer, chronic obstructive pulmonary disease, coronary hear disease, diabetes, stroke and all other conditions) and all cause mortality for the period September 2004 to August 2005. Multilevel logistic regression models explored the association between health outcomes (hospital admission and death) and practice QOF scores (clinical, additional services and organisational domains), age, sex and socio-economic deprivation.

Results
Higher clinical domain scores were generally associated with lower admission rates and this was significant for cancer and other conditions in PCT 2. Higher scores in the additional services domain were associated with higher admission rates, significantly so for asthma, CHD, stroke and other conditions in PCT 1 and cancer in PCT 2. Little association was observed between the organisational domain scores and admissions. The relationship between the QOF variables and mortality was less clear. Being female was associated with fewer admissions for cancer and CHD and lower mortality rates. Increasing age was mainly associated with an increased number of events. Increasing deprivation was associated with higher admission rates for all conditions and with higher mortality rates.

Conclusion
The associations between QOF scores and emergency admissions and mortality were small and inconsistent, whilst the impact of socio-economic deprivation on the outcomes was much stronger. These results have implications for the use of target-based remuneration of general practitioners and emphasise the need to tackle inequalities and improve the health of disadvantaged groups and the population as a whole.
Molecular signatures define two main classes of meningiomas
Authors: Carvalho Lucia Helena , Smirnov Ivan , Baia Gilson S , Modrusan Zora , Smith Justin S , Jun Peter , Costello Joseph F , McDermott Michael W , VandenBerg Scott R , Lal Anita 
Published: October 2007

AbstractBackgroundMeningiomas are common brain tumors that are classified into three World Health Organization grades (benign, atypical and malignant) and are molecularly ill-defined tumors. The purpose of this study was identify molecular signatures unique to the different grades of meningiomas and to unravel underlying molecular mechanisms driving meningioma tumorigenesis.ResultsWe have used a combination of gene expression microarrays and array comparative genomic hybridization (aCGH) to show that meningiomas of all three grades fall into two main molecular groups designated 'low-proliferative' and 'high-proliferative' meningiomas. While all benign meningiomas fall into the low-proliferative group and all malignant meningiomas fall into the high-proliferative group, atypical meningiomas distribute into either one of these groups. High-proliferative atypical meningiomas had an elevated median MIB-1 labeling index and a greater frequency of copy number aberrations (CNAs) compared to low-proliferative atypical meningiomas. Additionally, losses on chromosome 6q, 9p, 13 and 14 were found exclusively in the high-proliferative meningiomas. We have identified genes that distinguish benign low-proliferative meningiomas from malignant high-proliferative meningiomas and have found that gain of cell-proliferation markers and loss of components of the transforming growth factor-beta signaling pathway were the major molecular mechanisms that distinguish these two groups.ConclusionCollectively, our data suggests that atypical meningiomas are not a molecularly distinct group but are similar to either benign or malignant meningiomas. It is anticipated that identified molecular and CNA markers will potentially be more accurate prognostic markers of meningiomas.
Variable expressivity of the tumour suppressor protein TRP53 in cryopreserved human blastocysts
Authors: Chandrakanthan Vashe , Chami Omar , Stojanov Tomas , O'Neill Chris 
Published: October 2007

Abstract
In a mouse model, in vitro fertilization or extended embryo culture leads to the increased expression of TRP53 in susceptible embryos. Ablation of the TRP53 gene improved embryo viability indicating that increased expression of TRP53 is a cause of the reduction of embryo viability resulting from in vitro fertilization or embryo culture. This study investigates the status of TRP53 expression in human embryos produced by intracytoplasmic sperm injection. Following fertilization, embryos were cultured for 96 h and then cryopreserved. Immediately upon thawing they were fixed in formaldehyde and subjected to immunostaining for TRP53. Staining was visualized by confocal microscopy. Negative controls were incubated with isotype control immunoglobulin and showed negligible staining. All embryos showed TRP53 staining above negative controls. TRP53 staining was heterogenous within and between embryos. An embryo that showed retarded development showed high levels of TRP53 expression. A blastocyst that had a collapsed blastocoel also showed high levels of TRP53 compared to morphologically normal blastocysts. Most TRP53 staining was in the region of the nucleus. Morphologically normal blastocysts tended to show little nuclear accumulation of stain. However, some cells within these embryos had high levels of nuclear TRP53 expression. The results show that embryos have varying sensitivity to the stresses of production and culture in vitro, and this resulted in variable expressivity of TRP53.
Mycobacterium avium complex immune reconstitution inflammatory syndrome: Long term outcomes
Authors: Riddell James , Kaul Daniel R , Karakousis Petros C , Gallant Joel E , Mitty Jennifer , Kazanjian Powel H 
Published: October 2007

Abstract

Background
To describe long term outcomes of Mycobacterium avium complex (MAC) immune reconstitution inflammatory syndrome (IRIS).

Methods
Cases of MAC IRIS were retrospectively identified at four HIV clinics (Michigan, Maryland, Rhode Island, and Indiana) from 1996–2004. Patients were included if they were initially diagnosed with AIDS and found to have evidence of focal MAC infection documented by tissue culture or PCR after initiating HAART, and at least 6 months of follow up.

Results
Among the 20 patients included, the mean age was 40 years, mean CD4 cell count was 24/mm3 at pretreatment baseline and 100/mm3 at time of MAC IRIS diagnosis. Sites of disease included lymph nodes (15 patients [8 peripheral, 8 abdominal and 1 peripheral and abdominal]), gastrointestinal tract (7) and liver (3). Sixteen patients (80%) responded to treatment and were disease free after a mean of 17.4 months of therapy for MAC IRIS; IRIS therapy was withdrawn in 6 without relapse. Four patients (non-responder group) had persistent or relapsing disease despite 27 months of ongoing MAC IRIS treatment. At the time of resolution or last follow-up, the mean CD4 cell count and viral load was 143/mm3 and 7,000 c/mL for responders, and 65/mm3 and 17,000 c/mL for non-responders, respectively. Most patients with peripheral adenopathy were responders (7/8; 88%); many with abdominal adenopathy (4/8; 50%) were nonresponders.

Conclusion
The majority of patients with MAC IRIS eventually responded to treatment. Our sample size was not adequate to perform statistical analysis, but there was a tendency towards adequate CD4 response to HAART and peripheral rather than intraabdominal adenopathy among responders.
Visualizing regulatory interactions in metabolic networks
Authors: Noack Stephan , Wahl Aljoscha , Qeli Ermir , Wiechert Wolfgang 
Published: October 2007

Abstract

Background

Direct visualization of data sets in the context of biochemical network drawings is one of the most appealing approaches in the field of data evaluation within systems biology. One important type of information that is very helpful in interpreting and understanding metabolic networks has been overlooked so far. Here we focus on the representation of this type of information given by the strength of regulatory interactions between metabolite pools and reaction steps.

Results

The visualization of such interactions in a given metabolic network is based on a novel concept defining the regulatory strength (RS) of effectors regulating certain reaction steps. It is applicable to any mechanistic reaction kinetic formula. The RS values are measures for the strength of an up- or down-regulation of a reaction step compared with the completely non-inhibited or non-activated state, respectively. One numerical RS value is associated to any effector edge contained in the network. The RS is approximately interpretable on a percentage scale where 100% means the maximal possible inhibition or activation, respectively, and 0% means the absence of a regulatory interaction. If many effectors influence a certain reaction step, the respective percentages indicate the proportion in which the different effectors contribute to the total regulation of the reaction step. The benefits of the proposed method are demonstrated with a complex example system of a dynamic E. coli network.

Conclusion

The presented visualization approach is suitable for an intuitive interpretation of simulation data of metabolic networks under dynamic as well as steady-state conditions. Huge amounts of simulation data can be analyzed in a quick and comprehensive way. An extended time-resolved graphical network presentation provides a series of information about regulatory interaction within the biological system under investigation.
Small non-coding RNAs, mammalian cells, and viruses: regulatory interactions?
Authors: Yeung Man Lung , Benkirane Monsef , Jeang Kuan-Teh 
Published: October 2007

AbstractRecent findings suggest that mammalian cells can use small non-coding RNAs (ncRNA) to regulate physiological viral infections. Here, we comment on several lines of evidence that support this concept. We discuss how viruses may in turn protect, suppress, evade, modulate, or adapt to the host cell's ncRNA regulatory schema.
Requirements for the selective degradation of CD4 receptor molecules by the human immunodeficiency virus type 1 Vpu protein in the endoplasmic reticulum
Authors: Binette Julie , Dubé Mathieu , Mercier Johanne , Halawani Dalia , Latterich Martin , Cohen Éric A 
Published: October 2007

Abstract

Background
HIV-1 Vpu targets newly synthesized CD4 receptor for rapid degradation by a process reminiscent of endoplasmic reticulum (ER)-associated protein degradation (ERAD). Vpu is thought to act as an adaptor protein, connecting CD4 to the ubiquitin (Ub)-proteasome degradative system through an interaction with β-TrCP, a component of the SCFβ-TrCP E3 Ub ligase complex.

Results
Here, we provide direct evidence indicating that Vpu promotes trans-ubiquitination of CD4 through recruitment of SCFβ-TrCP in human cells. To examine whether Ub conjugation occurs on the cytosolic tail of CD4, we substituted all four Ub acceptor lysine residues for arginines. Replacement of cytosolic lysine residues reduced but did not prevent Vpu-mediated CD4 degradation and ubiquitination, suggesting that Vpu-mediated CD4 degradation is not entirely dependent on the ubiquitination of cytosolic lysines and as such might also involve ubiquitination of other sites. Cell fractionation studies revealed that Vpu enhanced the levels of ubiquitinated forms of CD4 detected in association with not only the ER membrane but also the cytosol. Interestingly, significant amounts of membrane-associated ubiquitinated CD4 appeared to be fully dislocated since they could be recovered following sodium carbonate salt treatment. Finally, expression of a transdominant negative mutant of the AAA ATPase Cdc48/p97 involved in the extraction of ERAD substrates from the ER membrane inhibited Vpu-mediated CD4 degradation.

Conclusion
Taken together, these results are consistent with a model whereby HIV-1 Vpu targets CD4 for degradation by an ERAD-like process involving most likely poly-ubiquitination of the CD4 cytosolic tail by SCFβ-TrCP prior to dislocation of receptor molecules across the ER membrane by a process that depends on the AAA ATPase Cdc48/p97.
The wild boar (Sus scrofa) Lymphocyte function-associated antigen-1 (CD11a/CD18) receptor: cDNA sequencing, structure analysis and comparison with homologues
Authors: Bergh Philippe GAC Vanden , Zecchinon Laurent LM , Fett Thomas , Desmecht Daniel JM 
Published: October 2007

AbstractBackgroundThe most predominantbeta2-integrin lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18,alphaLbeta2), expressed on all leukocytes, is essential for many adhesive functions of the immune system. Interestingly, RTX toxin-producing bacteria specifically target this leukocytebeta2-integrin which exacerbates lesions and disease development.ResultsThis study reports the sequencing of the wild boarbeta2-integrin CD11a and CD18 cDNAs. Predicted CD11a and CD18 subunits share all the main structural characteristics of their mammalian homologues, with a larger interspecies conservation for the CD18 than the CD11a. Besides these strong overall similarities, wild boar and domestic pig LFA-1 differ by 2 (CD18) and 1 or 3 (CD11a) substitutions, of which one is located in the crucial I-domain (CD11a, E168D).ConclusionAs most wild boars are seropositive to the RTX toxin-producing bacteriumActinobacillus pleuropneumoniaeand because they have sustained continuous natural selection, future studies addressing the functional impact of these polymorphisms could bring interesting new information on the physiopathology ofActinobacillus pleuropneumoniae-associated pneumonia in domestic pigs.
Neutrophil granulocytes uniquely express, among human blood cells, high levels of Methionine-sulfoxide-reductase enzymes
Authors: Achilli Cesare , Ciana Annarita , Rossi Antonio , Balduini Cesare , Minetti Giampaolo 
Published: October 2007

AbstractL-Methionine (Met), in its free form or when inserted in proteins, is sensitive to oxidation of its thioether group by reactive oxygen species from exogenous or endogenous sources. Two stable diastereomers of Met sulfoxide [Met-(O)] may be formed [Met-S-(O) and Met-R-(O)], but these can be reduced by two classes of Methionine-sulfoxide-reductase (Msr) enzymes: MsrA, which reduces the S, and MsrB, which reduces the R sulfoxide. In this study, we have examined the levels of expression of Msr in human blood cells by enzymatic activity assay, Western blotting, and RT-PCR of purified populations of polymorphonuclear neutrophils and eosinophils, mononuclear cells, platelets, and erythrocytes. Our data indicate that of the blood cells analyzed, neutrophils expressed the highest activity, which was mainly of MsrB type. During degranulation of activated neutrophils, Msr activity was not released but remained confined within the cell, indicating a non-granular localization. Immunoprecipitation and RT-PCR studies indicated the almost complete lack of mitochondrial forms of Msrs in granulocytes. It is thus likely that Msrs are important as antioxidant/repair systems for neutrophils, cells with enormous capacity for the generation of reactive oxidants and hence, susceptible to oxidative damage.
Distinct receptor repertoire formation in mouse NK cell subsets regulated by MHC class I expression
Authors: Hayakawa Yoshihiro , Watt Sally V , Takeda Kazuyoshi , Smyth Mark J 
Published: October 2007

AbstractThe acquisition of inhibitory MHC-specific receptors occurs during NK cell differentiation and has been considered important in regulating NK cell responsiveness. NK cell differentiation has been studied on the basis of cell surface phenotype, function, and proliferative capacity. Together with phenotypically immature Mac-1lo NK cells, the mature Mac-1hi NK cell pool can be dissected further into two functionally distinct CD27hi and CD27lo subsets. Two major inhibitory receptors, CD94/NKG2A and Ly-49, are expressed on mouse NK cells. The acquisition of the CD94/NKG2A receptor seems to be an early event, whereas Ly-49 receptor expression is considered a relatively late event during NK cell ontogeny. In this study, we demonstrated a distinct NK cell inhibitory receptor repertoire formation within mature NK cell populations as defined by Mac-1 and CD27. By analyzing mice deficient in MHC class I expression or NKG2D ligand transgenic mice, we have shown that the inhibitory receptor repertoire can be modulated according to the differentiation/maturation status of NK cells, and the receptor acquisition is imprinted at an early stage of NK cell development by MHC class I interactions.