bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allopolyploid speciation and ongoing backcrossing between diploid progenitor and tetraploid progeny lineages in the Achillea millefoliumspecies complex: analyses of single-copy nuclear genes and genomic AFLP
Authors: Ma Jin-Xiu , Li Yan-Nan , Vogl Claus , Ehrendorfer Friedrich , Guo Yan-Ping 
Published: April 2010

AbstractBackgroundIn the flowering plants, many polyploid species complexes display evolutionary radiation. This could be facilitated by gene flow between otherwise separate evolutionary lineages in contact zones.Achillea collinais a widespread tetraploid species within theAchillea millefoliumpolyploid complex (Asteraceae-Anthemideae). It is morphologically intermediate between the relic diploids,A. setacea-2x in xeric andA. asplenifolia-2x in humid habitats, and often grows in close contact with either of them. By analyzing DNA sequences of two single-copy nuclear genes and the genomic AFLP data, we assess the allopolyploid origin ofA. collina-4x from ancestors corresponding toA. setacea-2x andA. asplenifolia-2x, and the ongoing backcross introgression between these diploid progenitor and tetraploid progeny lineages.ResultsIn both the ncpGSand thePgiCgene tree, haplotype sequences of the diploidA. setacea-2x andA. asplenifolia-2x group into two clades corresponding to the two species, though lineage sorting seems incomplete for thePgiCgene. In contrast,A. collina-4x and its suspected backcross plants show homeologous gene copies: sequences from the same tetraploid individual plant are placed in both diploid clades. Semi-congruent splits of an AFLP Neighbor Net link not onlyA. collina-4x to both diploid species, but some 4x individuals in a polymorphic population with mixed ploidy levels toA. setacea-2x on one hand and toA. collina-4x on the other, indicating allopolyploid speciation as well as hybridization across ploidal levels.ConclusionsThe findings of this study clearly demonstrate the hybrid origin ofAchillea collina-4x, the ongoing backcrossing between the diploid progenitor and their tetraploid progeny lineages. Such repeated hybridizations are likely the cause of the great genetic and phenotypic variation and ecological differentiation of the polyploid taxa inAchillea millefoliumagg.
Dissecting grain yield pathways and their interactions with grain dry matter content by a two-step correlation approach with maize seedling transcriptome
Authors: Fu Junjie , Thiemann Alexander , Schrag Tobias A , Melchinger Albrecht E , Scholten Stefan , Frisch Matthias 
Published: April 2010

Abstract

Background
The importance of maize for human and animal nutrition, but also as a source for bio-energy is rapidly increasing. Maize yield is a quantitative trait controlled by many genes with small effects, spread throughout the genome. The precise location of the genes and the identity of the gene networks underlying maize grain yield is unknown. The objective of our study was to contribute to the knowledge of these genes and gene networks by transcription profiling with microarrays.

Results
We assessed the grain yield and grain dry matter content (an indicator for early maturity) of 98 maize hybrids in multi-environment field trials. The gene expression in seedlings of the parental inbred lines, which have four different genetic backgrounds, was assessed with genome-scale oligonucleotide arrays. We identified genes associated with grain yield and grain dry matter content using a newly developed two-step correlation approach and found overlapping gene networks for both traits. The underlying metabolic pathways and biological processes were elucidated. Genes involved in sucrose degradation and glycolysis, as well as genes involved in cell expansion and endocycle were found to be associated with grain yield.

Conclusions
Our results indicate that the capability of providing energy and substrates, as well as expanding the cell at the seedling stage, highly influences the grain yield of hybrids. Knowledge of these genes underlying grain yield in maize can contribute to the development of new high yielding varieties.
Outbreak of leptospirosis among triathlon participants in Germany, 2006
Authors: Brockmann Stefan , Piechotowski Isolde , Bock-Hensley Oswinde , Winter Christian , Oehme Rainer , Zimmermann Stefan , Hartelt Katrin , Luge Enno , Nöckler Karsten , Schneider Thomas , Stark Klaus , Jansen Andreas 
Published: April 2010

Abstract

Background
In August 2006, a case of leptospirosis occurred in an athlete after a triathlon held around Heidelberg and in the Neckar river. In order to study a possible outbreak and to determine risk factors for infection an epidemiological investigation was performed.

Methods
Participants of the triathlon were contacted by e-mail and were asked to fill out a standardized questionnaire. In addition, they were asked to supply a serum sample for laboratory diagnosis of leptospirosis. A confirmed case patient was defined as a clinical case (i.e. fever and at least one additional symptom suggestive for leptospirosis) with at least two of the following tests positive: ELISA IgM, latex agglutination testing, or microscopic agglutination testing. Rainfall and temperature records were obtained.

Results
A total of 142 of 507 triathletes were contacted; among these, five confirmed leptospirosis cases were found. Open wounds were identified as the only significant risk factor for illness (p = 0.02). Heavy rains that preceded the swimming event likely increased leptospiral contamination of the Neckar River.

Discussion
This is the first outbreak of leptospirosis related to a competitive sports event in Germany. Among people with contact to freshwater, the risk of contracting leptospirosis should be considered by health care providers also in temperate countries, particularly in the summer after heavy rains.
Genetic modifiers of Hb E/β0 thalassemia identified by a two-stage genome-wide association study
Authors: Sherva Richard , Sripichai Orapan , Abel Kenneth , Ma Qianli , Whitacre Johanna , Angkachatchai Vach , Makarasara Wattanan , Winichagoon Pranee , Svasti Saovaros , Fucharoen Suthat , Braun Andreas , Farrer Lindsay A 
Published: April 2010

Abstract

Background
Patients with Hb E/β0 thalassemia display remarkable variability in disease severity. To identify genetic modifiers influencing disease severity, we conducted a two-stage genome scan in groups of 207 mild and 305 severe unrelated patients from Thailand with Hb E/β0 thalassemia and normal α-globin genes.

Methods
First, we estimated and compared the allele frequencies of approximately 110,000 gene-based single nucleotide polymorphisms (SNPs) in pooled DNAs from different severity groups. The 756 SNPs that showed reproducible allelic differences at P < 0.02 by pooling were selected for individual genotyping.

Results
After adjustment for age, gender and geographic region, logistic regression models showed 50 SNPs significantly associated with disease severity (P < 0.05) after Bonferroni adjustment for multiple testing. Forty-one SNPs in a large LD block within the β-globin gene cluster had major alleles associated with severe disease. The most significant was bthal_bg200 (odds ratio (OR) = 5.56, P = 2.6 × 10-13). Seven SNPs in two distinct LD blocks within a region centromeric to the β-globin gene cluster that contains many olfactory receptor genes were also associated with disease severity; rs3886223 had the strongest association (OR = 3.03, P = 3.7 × 10-11). Several previously unreported SNPs were also significantly associated with disease severity.

Conclusions
These results suggest that there may be an additional regulatory region centromeric to the β-globin gene cluster that affects disease severity by modulating fetal hemoglobin expression.
Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation
Authors: Kirschning Carsten J , Dreher Stefan , Maaß Björn , Fichte Sylvia , Schade Jutta , Köster Mario , Noack Andreas , Lindenmaier Werner , Wagner Hermann , Böldicke Thomas 
Published: April 2010

AbstractBackgroundToll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser)3amino acid sequence.ResultsCoexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV)-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM). Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well as TNFα translation and release by macrophages were largely abrogated upon transduction of αT2ib. αT2ib was expressed in BMM and splenocytes over 6 days upon systemic infection with AdVαT2ib. Systemic transduction applying AdVαT2ib rendered immune cells largely non-responsive to tripalmitoyl-peptide challenge. Our results show persistent paralysis of TLR2 activity and thus inhibition of immune activation.ConclusionThe generated anti-TLR2 scFv intrabody inhibits specifically and very efficiently TLR2 ligand-driven cell activationin vitroandex vivo. This indicates a therapeutic potential of αT2ib in microbial or viral infections.
Factors that affect mass transport from drug eluting stents into the artery wall
Authors: O'Connell Barry M , McGloughlin Tim M , Walsh Michael T 
Published: April 2010

Abstract
Coronary artery disease can be treated by implanting a stent into the blocked region of an artery, thus enabling blood perfusion to distal vessels. Minimally invasive procedures of this nature often result in damage to the arterial tissue culminating in the re-blocking of the vessel. In an effort to alleviate this phenomenon, known as restenosis, drug eluting stents were developed. They are similar in composition to a bare metal stent but encompass a coating with therapeutic agents designed to reduce the overly aggressive healing response that contributes to restenosis. There are many variables that can influence the effectiveness of these therapeutic drugs being transported from the stent coating to and within the artery wall, many of which have been analysed and documented by researchers. However, the physical deformation of the artery substructure due to stent expansion, and its influence on a drugs ability to diffuse evenly within the artery wall have been lacking in published work to date. The paper highlights previous approaches adopted by researchers and proposes the addition of porous artery wall deformation to increase model accuracy.
Labelling of live cells using fluorescent aptamers: binding reversal with DNA nucleases
Authors: Terazono Hideyuki , Anzai Yu , Soloviev Mikhail , Yasuda Kenji 
Published: April 2010

Abstract
A reversible cell labelling method has been developed for non-destructive and non-invasive cell labelling and purification. Our method uses high affinity single strand DNA (ssDNA) aptamers against surface exposed target molecules on cells. The aptamers are subsequently removed from the cell surface using DNase nuclease treatment. We exemplified our method by labelling human acute lymphoblastic leukemia cells with Qdot-ssDNA aptamers, and restoring them to the label-free condition by treatment with Benzonase. Binding of the fluorescent-aptamers to the cells was evaluated by measuring fluorescence intensity and was further confirmed using flow cytometry. Removal of the aptamers can be achieved in ~10 min by the DNase nuclease digestion. Incubation of cells with aptamers or with the nucleases results in no apparent damage to the cells and does not affect their growth rates. The latter were equivalent to the rates measured for the untreated cells. Our method provides an alternative to traditional antibody-based techniques and could be especially suitable for non-invasive reversible cell labelling and cell separations where maintaining native cell activity is needed.
Decay accelerating factor (CD55) protects neuronal cells from chemical hypoxia-induced injury
Authors: Wang Ying , Li Yansong , Dalle Lucca Shawn L , Simovic Milomir , Tsokos George C , Dalle Lucca Jurandir J 
Published: April 2010

AbstractBackgroundActivated complement system is known to mediate neuroinflammation and neurodegeneration following exposure to hypoxic-ischemic insults. Therefore, inhibition of the complement activation cascade may represent a potential therapeutic strategy for the management of ischemic brain injury. Decay-accelerating factor (DAF, also known as CD55) inhibits complement activation by suppressing the function of C3/C5 convertases, thereby limiting local generation or deposition of C3a/C5a and membrane attack complex (MAC or C5b-9) production. The present study investigates the ability of DAF to protect primary cultured neuronal cells subjected to sodium cyanide (NaCN)-induced hypoxia from degeneration and apoptosis.MethodsCultured primary cortical neurons from embryonic Sprague-Dawley rats were assigned one of four groups: control, DAF treatment alone, hypoxic, or hypoxic treated with DAF. Hypoxic cultures were exposed to NaCN for 1 hour, rinsed, followed by 24 hour exposure to 200 ng/ml of recombinant human DAF in normal medium. Human DAF was used in the present study and it has been shown to effectively regulate complement activation in rats. Neuronal cell function, morphology and viability were investigated by measuring plateau depolarization potential, counting the number dendritic spines, and observing TUNEL and MTT assays. Complement C3, C3a, C3a receptor (R) production, C3a-C3aR interaction and MAC formation were assessed along with the generation of activated caspase-9, activated caspase-3, and activated Src.ResultsWhen compared to controls, hypoxic cells had fewer dendritic spines, reduced plateau depolarization accompanied by increased apoptotic activity and accumulation of MAC, as well as up-regulation of C3, C3a and C3aR, enhancement of C3a-C3aR engagement, and elevated caspase and Src activity. Treatment of hypoxic cells with 200 ng/ml of recombinant human DAF resulted in attenuation of neuronal apoptosis and exerted significant protection against neuronal dendritic spine loss and plateau depolarization reduction. Furthermore, treatment with DAF resulted in decreased accumulation of C3a, MAC, C3a-C3aR interaction, caspase-9, activated caspase-3, and pTyr416-Src (activated Src) tyrosine kinase.ConclusionDAF was found to reduce neuronal cell death and apoptosis in NaCN induced hypoxia. This effect is attributed to the ability of DAF to limit complement activation and inhibit the activity of Src and caspases 9 and 3. This study supports the inhibiting of complement as a neuroprotective strategy against CNS ischemia/reperfusion injury.
CNAReporter: a GenePattern pipeline for the generation of clinical reports of genomic alterations
Authors: Kotliarov Yuri , Bozdag Serdar , Cheng Hangjiong , Wuchty Stefan , Zenklusen Jean-Claude , Fine Howard A 
Published: April 2010

Abstract

Background
Genomic copy number alterations are widely associated with a broad range of human tumors and offer the potential to be used as a diagnostic tool. Especially in the emerging era of personalized medicine medical informatics tools that allow the fast visualization and analysis of genomic alterations of a patient's genomic profile for diagnostic and potential treatment purposes increasingly gain importance.

Results
We developed CNAReporter, a software tool that allows users to visualize SNP-specific data obtained from Affymetrix arrays and generate PDF-reports as output. We combined standard algorithms for the analysis of chromosomal alterations, utilizing the widely applied GenePattern framework. As an example, we show genome analyses of two patients with distinctly different CNA profiles using the tool.

Conclusions
Glioma subtypes, characterized by different genomic alterations, are often treated differently but can be difficult to differentiate pathologically. CNAReporter offers a user-friendly way to visualize and analyse genomic changes of any given tumor genomic profile, thereby leading to an accurate diagnosis and patient-specific treatment.
Pulmonary edema and blood volume after aneurysmal subarachnoid hemorrhage: a prospective observational study
Authors: Hoff Reinier G , Rinkel Gabriel JE , Verweij Bon H , Algra Ale , Kalkman Cor J 
Published: April 2010

Abstract
Introduction
Pulmonary edema (PED) is a severe complication after aneurysmal subarachnoid hemorrhage (SAH). PED is often treated with diuretics and a reduction in fluid intake, but this may cause intravascular volume depletion, which is associated with secondary ischemia after SAH. We prospectively studied intravascular volume in SAH patients with and without PED.

Methods
Circulating blood volume (CBV) was determined daily during the first 10 days after SAH by means of pulse dye densitometry. CBV of 60-80 ml/kg was considered normal. PED was diagnosed from clinical signs and characteristic bilateral pulmonary infiltrates on the chest radiograph. We compared CBV, cardiac index, and fluid balance between patients with and without PED with weighted linear regression, taking into account only measurements from the first day after SAH through to the day on which PED was diagnosed. Differences were adjusted for age, bodyweight, and clinical condition.

Results
In total, 102 patients were included, 17 of whom developed PED after a mean of 4 days after SAH. Patients developing PED had lower mean CBV (56.6 ml/kg) than did those without PED (66.8 ml/kg). The mean difference in CBV was -11.3 ml/kg (95% CI, -16.5 to -6.1); adjusted mean difference, -8.0 ml/kg (95% CI, -14.0 to -2.0). After adjusting, no differences were found in cardiac index or fluid balance between patients with and without PED.

Conclusions
SAH patients developing pulmonary edema have a lower blood volume than do those without PED and are hypovolemic. Measures taken to counteract pulmonary edema must be balanced against the risk of worsening hypovolemia.

Trial registration
NTR1255.
One-year mortality, quality of life and predicted life-time cost-utility in critically ill patients with acute respiratory failure
Authors: Linko Rita , Suojaranta-Ylinen Raili , Karlsson Sari , Ruokonen Esko , Varpula Tero , Pettilä Ville ,   the FINNALI study investigators
Published: April 2010

Abstract
Introduction
High daily intensive care unit (ICU) costs are associated with the use of mechanical ventilation (MV) to treat acute respiratory failure (ARF), and assessment of quality of life (QOL) after critical illness and cost-effectiveness analyses are warranted.

Methods
Nationwide, prospective multicentre observational study in 25 Finnish ICUs. During an eight-week study period 958 consecutive adult ICU patients were treated with ventilatory support over 6 hours. Of those 958, 619 (64.6%) survived one year, of whom 288 (46.5%) answered the quality of life questionnaire (EQ-5D). We calculated EQ-5D index and predicted lifetime quality-adjusted life years (QALYs) gained using the age- and sex-matched life expectancy for survivors after one year. For expired patients the exact lifetime was used. We divided all hospital costs for all ARF patients by the number of hospital survivors, and by all predicted lifetime QALYs. We also adjusted for those who died before one year and for those with missing QOL to be able to estimate the total QALYs.

Results
One-year mortality was 35% (95% CI 32 to 38%). For the 288 respondents median [IQR] EQ-5D index after one year was lower than that of the age- and sex-matched general population 0.70 [0.45 to 0.89] vs. 0.84 [0.81 to 0.88]. For these 288, the mean (SD) predicted lifetime QALYs was 15.4 (13.3). After adjustment for missing QOL the mean predicted lifetime (SD) QALYs was 11.3 (13.0) for all the 958 ARF patients. The mean estimated costs were 20.739 € per hospital survivor, and mean predicted lifetime cost-utility for all ARF patients was 1391 € per QALY.

Conclusions
Despite lower health-related QOL compared to reference values, our result suggests that cost per hospital survivor and lifetime cost-utility remain reasonable regardless of age, disease severity, and type or duration of ventilation support in patients with ARF.
Standard International Prognostic Index Remains a Valid Predictor of Outcome for Patients With Aggressive CD20+B-Cell Lymphoma in the Rituximab Era
Authors: Ziepert Marita , Hasenclever Dirk , Kuhnt Evelyn , Glass Bertram , Schmitz Norbert , Pfreundschuh Michael , Loeffler Markus 
Published: April 2010

PurposeThe International Prognostic Index (IPI) is widely used for risk stratification of patients with aggressive B-cell lymphoma. The introduction of rituximab has markedly improved outcome, and R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisone) has become the standard treatment for CD20+diffuse large B-cell lymphoma. To investigate whether the IPI has maintained its power for risk stratification when rituximab is combined with CHOP, we analyzed the prognostic relevance of IPI in three prospective clinical trials.Patients and MethodsIn total, 1,062 patients treated with rituximab were included (MabThera International Trial [MInT], 380 patients; dose-escalated regimen of cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (MegaCHOEP) trial, 72 patients; CHOP + rituximab for patients older than age 60 years [RICOVER-60] trial, 610 patients). A multivariate proportional hazards modeling was performed for single IPI factors under rituximab on event-free, progression-free, and overall survival.ResultsIPI score was significant for all three end points. Rituximab significantly improved treatment outcome within each IPI group resulting in a quenching of the Kaplan-Meier estimators. However, IPI was a significant prognostic factor in all three end points and the ordering of the IPI groups remained valid. The relative risk estimates of single IPI factors and their order in patients treated with R-CHOP were similar to those found with CHOP.ConclusionThe effects of rituximab were superimposed on the effects of CHOP with no interactions between chemotherapy and antibody therapy. These results demonstrate that the IPI is still valid in the R-CHOP era.