bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three novel ABCC5 splice variants in human retina and their role as regulators of ABCC5 gene expression
Authors: Stojic Jelena , Stöhr Heidi , Weber Bernhard HF 
Published: May 2007

Abstract

Background
The ABCC5 gene encodes an organic anion pump of the ATP-binding cassette (ABC) transporter family, subclass C. The exact physiological function of ABCC5 however is not known. Here, we have isolated three novel ABCC5 splice variants and characterized their role in the regulation of ABCC5 gene expression.

Results
Two additional exons within intron 5 of the ABCC5 gene were identified; one of the exons exhibits alternative donor splice sites. Differential usage of these exons generates three short ABCC5 transcripts named ABCC5_SV1, ABCC5_SV2 and ABCC5_SV3. The variants share the first five exons with the ABCC5 gene but differ in their 3' sequences. ABCC5 and its novel isoforms are abundantly expressed in the human retina. Splice variant ABCC5_SV1 and ABCC5_SV2 contain premature stop codons. While inhibition of nonsense-mediated mRNA decay selectively stabilized ABCC5_SV1 but not ABCC5_SV2, the amount of full length ABCC5 mRNA was simultaneously reduced. A negative regulatory effect on full length ABCC5 expression was also observed when the ABCC5 isoforms were silenced with siRNA duplexes. Finally, we show that the evolutionarily conserved ABCC5_SV2 transcript is translated into a protein abundantly present in endothelial cells of inner retinal blood vessels and along RPE membranes.

Conclusion
Our data suggest that alternative splicing of the ABCC5 gene has functional consequences by modulating ABCC5 gene expression. In addition, at least one ABCC5 splice variant is protein-coding and produces a truncated ABCC5 protein isoform with thus far unknown functional properties in the retina.
Novel in vivo targets of ΔNp63 in keratinocytes identified by a modified chromatin immunoprecipitation approach
Authors: Birkaya Barbara , Ortt Kori , Sinha Satrajit 
Published: May 2007

Abstract

Background
p63 is a transcription factor that plays an important role in skin epidermal development and differentiation. The p63 gene encodes for two major protein isoforms, those containing an amino-terminal trans-activation domain (TAp63) and those lacking this domain (ΔNp63). Both the TA and ΔN transcripts are also alternatively spliced at the 3' end producing proteins with unique C-termini that are designated as α, β and γ isoforms. Recent research has suggested that ΔNp63 is the predominant isoform expressed and active in keratinocytes.

Results
To better elucidate the biological role of p63 in regulating gene expression in keratinocytes we performed chromatin immunoprecipitation (ChIP) experiments with ΔNp63-specific antibodies. We included an additional step in the ChIP procedure to enrich for ΔNp63 targets by screening the library of immunoprecipitated DNA for its ability to bind recombinant GST-ΔNp63. Cloning of ΔNp63-ChIP-derived DNA fragments identified more than 60 potential ΔNp63 target loci that were located close to or embedded within known or predicted genes. Identity of these target genes suggests that they may participate in a myriad of cellular processes including transcriptional regulation, signaling and metabolism. Here we confirm the binding of ΔNp63 to several of these genomic loci both by EMSA and replicate ChIP assays. Finally we show that the expression of many of these target genes is altered when ΔNp63 levels in keratinocytes are reduced by siRNA, further confirming that these are bona fide targets.

Conclusion
This unbiased genomic approach has allowed us to uncover functional targets of ΔNp63 and serves as the initial step in further analysis of the transcriptional regulatory mechanisms that are governed by p63 in keratinocytes.
A set of multiplex panels of microsatellite markers for rapid molecular characterization of rice accessions
Authors: Pessoa-Filho Marco , Beló André , Alcochete António AN , Rangel Paulo HN , Ferreira Márcio E 
Published: May 2007

Abstract

Background
This study aimed to analyze the efficiency of three new microsatellite multiplex panels, which were designed to evaluate a total of 16 loci of the rice genome, based on single PCR reactions of each panel. A sample of 548 accessions of traditional upland rice landraces collected in Brazil in the last 25 years was genotyped, a database of allelic frequencies was established, estimates of genetic parameters were performed and analysis of genetic structure of the collection was developed.

Results
The three panels yielded a combined matching probability of 6.4 × 10-21, polymorphism information content (PIC) of 0.637, and a combined power of exclusion greater than 99.99%. A few samples presented a genetic background of indica rice. The 16 SSR loci produced a total of 229 alleles. Gene diversity values averaged 0.667, and PIC values averaged 0.637. Genetic structure analysis of the collection using a Bayesian approach detected three possible major clusters, with an overall F
ST value of 0.177. Important inputs on the knowledge about upland rice germplasm differentiations which happened in Brazil in the last few centuries were also achieved and are discussed.

Conclusion
The three multiplex panels described here represent a powerful tool for rice genetic analysis, offering a rapid and efficient option for rice germplasm characterization. The data gathered demonstrates the feasibility of genotyping extensive germplasm collections using panels of multiplexed microsatellite markers. It contributes to the advancement of research on large scale characterization and management of germplasm banks, as well as identification, protection and assessments of genetic relationship of rice germplasm.
Hygienic safety of reusable tap water filters (Germlyser®) with an operating time of 4 or 8 weeks in a haematological oncology transplantation unit
Authors: Daeschlein Georg , Krüger William H , Selepko Christian , Rochow Markus , Dölken Gottfried , Kramer Axel 
Published: May 2007

Abstract

Background
Microbial safe tap water is crucial for the safety of immunosuppressed patients.

Methods
To evaluate the suitability of new, reusable point-of-use filters (Germlyser®, Aquafree GmbH, Hamburg, Germany), three variations of a reusable filter with the same filter principle but with different outlets (with and without silver) and inner surface coating of the filter encasements (with and without nano-crystalline silver) were tested. The filter efficacy was monitored over 1, 4 and 8 weeks operating time in a haematological oncology transplantation unit equipped with 18 water outlets (12 taps, 6 showers).

Results
The filtered water fulfilled the requirements of absence of pathogens over time. From 348 samples, 8 samples (2.3%) exceeded 100 cfu/ml (no sample ≥ 500 cfu/ml). As no reprocessed filter exhibited 100% filter efficacy in the final quality control after each reprocessing, these contaminations could be explained by retrograde contamination during use.

Conclusion
As a consequence of the study, the manufacturer recommends changing filters after 4 weeks in high risk areas and after 8 weeks in moderate infectious risk areas, together with routine weekly alcohol-based surface disinfection and additionally in case of visible contamination. The filter efficacy of the 3 filters types did not differ significantly regarding total bacterial counts. Manual reprocessing proved to be insufficient. Using a validated reprocessing in a washer/disinfector with alkaline, acid treatment and thermic disinfection, the filters were effectively reprocessable and now provide tap water meeting the German drinking water regulations as well as the WHO guidelines, including absence of pathogens.
Renin-angiotensin-aldosterone system polymorphisms: a role or a hole in occurrence and long-term prognosis of acute myocardial infarction at young age
Authors: Franco Erica , Palumbo Luigi , Crobu Francesca , Anselmino Matteo , Frea Simone , Matullo Giuseppe , Piazza Alberto , Trevi Gian Paolo , Bergerone Serena 
Published: May 2007

Abstract

Background
The renin-angiotensin-aldosterone system (RAAS) is involved in the cardiovascular homeostasis as shown by previous studies reporting a positive association between specific RAAS genotypes and an increased risk of myocardial infarction. Anyhow the prognostic role in a long-term follow-up has not been yet investigated.
Aim of the study was to evaluate the influence of the most studied RAAS genetic Single Nucleotide Polymorphisms (SNPs) on the occurrence and the long-term prognosis of acute myocardial infarction (AMI) at young age in an Italian population.

Methods
The study population consisted of 201 patients and 201 controls, matched for age and sex (mean age 40 ± 4 years; 90.5% males). The most frequent conventional risk factors were smoke (p < 0.001), family history for coronary artery diseases (p < 0.001), hypercholesterolemia (p = 0.001) and hypertension (p = 0.002). The tested genetic polymorphisms were angiotensin converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AGTR1) A1166C and aldosterone synthase (CYP11B2) C-344T. Considering a long-term follow-up (9 ± 4 years) we compared genetic polymorphisms of patients with and without events (cardiac death, myocardial infarction, revascularization procedures).

Results
We found a borderline significant association of occurrence of AMI with the ACE D/I polymorphism (DD genotype, 42% in cases vs 31% in controls; p = 0.056). DD genotype remained statistically involved in the incidence of AMI also after adjustment for clinical confounders.
On the other hand, during the 9-year follow-up (65 events, including 13 deaths) we found a role concerning the AGTR1: the AC heterozygous resulted more represented in the event group (p = 0.016) even if not independent from clinical confounders. Anyhow the Kaplan-Meier event free curves seem to confirm the unfavourable role of this polymorphism.

Conclusion
Polymorphisms in RAAS genes can be important in the onset of a first AMI in young patients (ACE, CYP11B2 polymorphisms), but not in the disease progression after a long follow-up period. Larger collaborative studies are needed to confirm these results.
Can asthma control be improved by understanding the patient's perspective?
Authors: Horne Rob , Price David , Cleland Jen , Costa Rui , Covey Donna , Gruffydd-Jones Kevin , Haughney John , Henrichsen Svein Hoegh , Kaplan Alan , Langhammer Arnulf , Østrem Anders , Thomas Mike , van der Molen Thys , Virchow J Christian , Williams Siân 
Published: May 2007

Abstract

Background
Clinical trials show that asthma can be controlled in the majority of patients, but poorly controlled asthma still imposes a considerable burden. The level of asthma control achieved reflects the behaviour of both healthcare professionals and patients. A key challenge for healthcare professionals is to help patients to engage in self-management behaviours with optimal adherence to appropriate treatment. These issues are particularly relevant in primary care, where most asthma is managed. An international panel of experts invited by the International Primary Care Respiratory Group considered the evidence and discussed the implications for primary care practice.

Discussion

Causes of poor control

Clinical factors such as exposure to triggers and concomitant rhinitis are important but so are patient behavioural factors. Behaviours such as smoking and nonadherence may reduce the efficacy of treatment and patients' perceptions influence these behaviours. Perceptual barriers to adherence include doubting the need for treatment when symptoms are absent and concerns about potential adverse effects. Under-treatment may also be related to patients' underestimation of the significance of symptoms, and lack of awareness of achievable control.

Implications

Three key implications for healthcare professionals emerged from the debate. First, the need for simple tools to assess asthma control. Two approaches considered were the monitoring of biometric markers of control and questionnaires to record patient-reported outcomes. Second, to understand the reasons for poor control for individual patients, identifying both clinical (e.g. rhinitis) and behavioural factors (e.g. smoking and nonadherence to treatment). Third was the need to incorporate, within asthma review, an assessment of patient perspectives including their goals and aspirations and to elicit their beliefs and concerns about asthma and its treatment. This can be used as a basis for agreement between the healthcare professional and patient on a predefined target regarding asthma control and a treatment plan to achieve this.

Summary
Optimum review of asthma is essential to improve control. A key priority is the development of simple and effective tools for identifying poor control for individual patients coupled with a tailored approach to treatment to enable patients to set and achieve realistic goals for asthma control.
Rapid and specific biotin labelling of the erythrocyte surface antigens of both cultured and ex-vivo Plasmodium parasites
Authors: Sharling Lisa , Sowa Kordai MP , Thompson Joanne , Kyriacou Helen M , Arnot David E 
Published: May 2007

Abstract

Background
Sensitive detection of parasite surface antigens expressed on erythrocyte membranes is necessary to further analyse the molecular pathology of malaria. This study describes a modified biotin labelling/osmotic lysis method which rapidly produces membrane extracts enriched for labelled surface antigens and also improves the efficiency of antigen recovery compared with traditional detergent extraction and surface radio-iodination. The method can also be used with ex-vivo parasites.

Methods
After surface labelling with biotin in the presence of the inhibitor furosemide, detergent extraction and osmotic lysis methods of enriching for the membrane fractions were compared to determine the efficiency of purification and recovery. Biotin-labelled proteins were identified on silver-stained SDS-polyacrylamide gels.

Results
Detergent extraction and osmotic lysis were compared for their capacity to purify biotin-labelled Plasmodium falciparum and Plasmodium chabaudi erythrocyte surface antigens. The pellet fraction formed after osmotic lysis of P. falciparum-infected erythrocytes is notably enriched in suface antigens, including PfEMP1, when compared to detergent extraction. There is also reduced co-extraction of host proteins such as spectrin and Band 3.

Conclusion
Biotinylation and osmotic lysis provides an improved method to label and purify parasitised erythrocyte surface antigen extracts from both in vitro and ex vivo Plasmodium parasite preparations.
Selective activation of TCR-γδ+ cells in endemic Burkitt's lymphoma
Authors: Futagbi Godfred , Welbeck Jennifer E , Tetteh John Kweku A , Hviid Lars , Akanmori Bartholomew D 
Published: May 2007

AbstractBackgroundThe overlap in geographical distribution ofPlasmodium falciparummalaria and endemic Burkitt's lymphoma (eBL) – an aggressive Epstein-Barr virus (EBV)-associated B-cell tumour occurring almost exclusively in the tropics – strongly suggests a link between the two diseases. It is suspected that the polyclonal B-cell activation inP. falciparummalaria may precipitate a breakdown in homeostatic T-cell control of EBV-immortalized B-cell proliferation. Previous studies have suggested that a particular T-cell subset, characterized by expression of Vδ1+γδT-cell receptors, is important for maintaining B-cell homeostasis, both inP. falciparum- exposed populations and in individuals subject to polyclonal B-cell activation of other aetiology. The objective of the present study was, therefore, to characterize lymphocyte phenotypes and to investigate possible differences in T-cell subset composition and activation status inP. falciparum-exposed Ghanaian children with and without eBL.MethodsVenous blood samples in heparin from 21 eBL patients (mean age: 7.0 years; range: 3–11 years), referred to the Burkitt's Tumour Centre at Korle-Bu Teaching Hospital, Accra and 15 healthy, age and sex matched children, were stained with fluorescein isothiocyanate (FITC)-, phycoerythrin (PE)-, R-phycoerythrin (RPE)- and RPE-Cy5-conjugated antibodies (CD3, CD4, CD8, CD25, CD69, CD95, HLA-DR, TCR-γδ, Vδ1, Vδ3, Vγ9 and B-cells) and acquired on a flow cytometer.ResultsA reduction in the proportion of CD3+cells in eBL patients, due mainly to perturbations among TCR-γδ+cells was observed. In contrast, the proportions of CD4+or CD8+cells were relatively unaffected, as were the mean numbers of peripheral blood mononuclear cells.ConclusionSelective changes in numbers and activation status of TCR-γδ+cells occurs in Ghanaian children with eBL, a pattern which is similar toP. falciparum-induced changes. The data supports the hypothesis of a regulatory role for Vδ1+TcR-γδT-cells in maintaining B-cell homeostasis and provides insights into the pathogenesis of eBL.
Recovery of transplantable organs after cardiac or circulatory death: Transforming the paradigm for the ethics of organ donation
Authors: Verheijde Joseph L , Rady Mohamed Y , McGregor Joan 
Published: May 2007

AbstractOrgan donation after cardiac or circulatory death (DCD) has been introduced to increase the supply of transplantable organs. In this paper, we argue that the recovery of viable organs useful for transplantation in DCD is not compatible with the dead donor rule and we explain the consequential ethical and legal ramifications. We also outline serious deficiencies in the current consent process for DCD with respect to disclosure of necessary elements for voluntary informed decision making and respect for the donor's autonomy. We compare two alternative proposals for increasing organ donation consent in society: presumed consent and mandated choice. We conclude that proceeding with the recovery of transplantable organs from decedents requires a paradigm change in the ethics of organ donation. The paradigm change to ensure the legitimacy of DCD practice must include: (1) societal agreement on abandonment of the dead donor rule, (2) legislative revisions reflecting abandonment of the dead donor rule, and (3) requirement of mandated choice to facilitate individual participation in organ donation and to ensure that decisions to participate are made in compliance with the societal values of respect for autonomy and self-determination.
Proton-pump inhibitors are associated with a reduced risk for bleeding and perforated gastroduodenal ulcers attributable to non-steroidal anti-inflammatory drugs: a nested case-control study
Authors: Vonkeman Harald E , Fernandes Robert W , van der Palen Job , van Roon Eric N , van de Laar Mart AFJ 
Published: May 2007

AbstractTreatment with non-steroidal anti-inflammatory drugs (NSAIDs) is hampered by gastrointestinal ulcer complications, such as ulcer bleeding and perforation. The efficacy of proton-pump inhibitors in the primary prevention of ulcer complications arising from the use of NSAIDs remains unproven. Selective cyclooxygenase-2 (COX-2) inhibitors reduce the risk for ulcer complications, but not completely in high-risk patients. This study determines which patients are especially at risk for NSAID ulcer complications and investigates the effectiveness of different preventive strategies in daily clinical practice. With the use of a nested case-control design, a large cohort of NSAID users was followed for 26 months. Cases were patients with NSAID ulcer complications necessitating hospitalisation; matched controls were selected from the remaining cohort of NSAID users who did not have NSAID ulcer complications. During the observational period, 104 incident cases were identified from a cohort of 51,903 NSAID users with 10,402 patient years of NSAID exposure (incidence 1% per year of NSAID use, age at diagnosis 70.4 ± 16.7 years (mean ± SD), 55.8% women), and 284 matched controls. Cases were characterised by serious, especially cardiovascular, co-morbidity. In-hospital mortality associated with NSAID ulcer complications was 10.6% (incidence 21.2 per 100,000 NSAID users). Concomitant proton-pump inhibitors (but not selective COX-2 inhibitors) were associated with a reduced risk for NSAID ulcer complications (the adjusted odds ratio 0.33; 95% confidence interval 0.17 to 0.67; p = 0.002). Especially at risk for NSAID ulcer complications are elderly patients with cardiovascular co-morbidity. Proton-pump inhibitors are associated with a reduced risk for NSAID ulcer complications.
Cystatin C and beta2-microglobulin: markers of glomerular filtration in critically ill children
Authors: Herrero-Morín José David , Málaga Serafín , Fernández Nuria , Rey Corsino , Diéguez María Ángeles , Solís Gonzalo , Concha Andrés , Medina Alberto 
Published: May 2007

Abstract
Introduction
Parameters allowing regular evaluation of renal function in a paediatric intensive care unit (PICU) are not optimal. The aim of the present study was to analyse the utility of serum cystatin C and beta2-microglobulin (B2M) in detecting decreased glomerular filtration rate in critically ill children.

Methods
This was a prospective, observational study set in an eight-bed PICU. Twenty-five children were included. The inverses of serum creatinine, cystatin C, and B2M were correlated with creatinine clearance (CrC) using a 24-hour urine sample and CrC estimation by Schwartz formula (Schwartz). The diagnostic value of serum creatinine, cystatin C, and B2M to identify a glomerular filtration rate under 80 ml/minute per 1.73 m2 was evaluated using receiver operating characteristic (ROC) curve analysis.

Results
Mean age was 2.9 years (range, 0.1 to 13.9 years). CrC was less than 80 ml/minute per 1.73 m2 in 14 children, and Schwartz was less than 80 ml/minute per 1.73 m2 in 9 children. Correlations between inverse of B2M and CrC (r = 0.477) and between inverse of B2M and Schwartz (r = 0.697) were better than correlations between inverse of cystatin C and CrC (r = 0.390) or Schwartz (r = 0.586) and better than correlations between inverse of creatinine and CrC (r = 0.104) or Schwartz (r = 0.442). The ability of serum cystatin C and B2M to identify a CrC rate and a Schwartz CrC rate under 80 ml/minute per 1.73 m2 was better than that of creatinine (areas under the ROC curve: 0.851 and 0.792 for cystatin C, 0.802 and 0.799 for B2M, and 0.633 and 0.625 for creatinine).

Conclusion
Serum cystatin C and B2M were confirmed as easy and useful markers, better than serum creatinine, to detect acute kidney injury in critically ill children.
Water Drinking Induces Thermogenesis through Osmosensitive Mechanisms
Authors: Boschmann Michael , Steiniger Jochen , Franke Gabriele , Birkenfeld Andreas L. , Luft Friedrich C. , Jordan Jens 
Published: May 2007

Abstract
Context: Recently, we showed that drinking 500 ml water induces thermogenesis in normal-weight men and women.
Objective: We now repeated these studies in a randomized, controlled, crossover trial in overweight or obese otherwise healthy subjects (eight men and eight women), comparing also the effects of 500 ml isoosmotic saline or 50 ml water.
Results: Only 500 ml water increased energy expenditure by 24% over the course of 60 min after ingestion, whereas isoosmotic saline and 50 ml water had no effect. Heart rate and blood pressure did not change in these young, healthy subjects.
Conclusions: Our data exclude volume-related effects or gastric distension as the mediator of the thermogenic response to water drinking. Instead, we hypothesize the existence of a portal osmoreceptor, most likely an ion channel.