bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sinus venosus atrial septal defect in a 31-year-old female patient: a case for surgical repair
Authors: Gatzoulis M.A. , Giannakoulas G. 
Published: December 2010

A 31-yr-old female patient previously diagnosed with idiopathic pulmonary arterial hypertension (PAH) was referred to our centre for further evaluation. Cardiac magnetic resonance imaging (MRI) and echocardiography revealed a superior sinus venosus atrial septal defect (ASD) with partial anomalous pulmonary venous drainage. Following re-diagnosis, surgical repair was considered. Despite a disproportionately high mean pulmonary artery pressure (P̄pa) of 47 mmHg relative to the patient's age and defect, the decision to operate was based on the absence of oxygen desaturation (either at rest or during exercise), cyanosis or abnormally elevated haemoglobin. Other operability criteria included normal sinus rhythm at rest, vasoreactivity and a pulmonary to systemic blood flow ratio of 1.9 at rest.Surgical repair and continued advanced therapy with bosentan 125 mgb.i.d. and aspirin 75 mgo.d. proved successful, with post-operative improvements in exercise capacity and dyspnoea, and a reduction inP̄pato 25 mmHg. Keen to start a family, the risks of pregnancy were discussed. This case illustrates the importance of secondary PAH in sinus venosus ASD and the need to exclude a sinus venosus ASD in unexplained right ventricular dilatation. Access to expertise in congenital heart disease and use of cardiac MRI can improve diagnosis and, in turn, treatment decisions.
A hybrid blob-slice model for accurate and efficient detection of fluorescence labeled nuclei in 3D
Authors: Santella Anthony , Du Zhuo , Nowotschin Sonja , Hadjantonakis Anna-Katerina , Bao Zhirong 
Published: November 2010

Abstract

Background
To exploit the flood of data from advances in high throughput imaging of optically sectioned nuclei, image analysis methods need to correctly detect thousands of nuclei, ideally in real time. Variability in nuclear appearance and undersampled volumetric data make this a challenge.

Results
We present a novel 3D nuclear identification method, which subdivides the problem, first segmenting nuclear slices within each 2D image plane, then using a shape model to assemble these slices into 3D nuclei. This hybrid 2D/3D approach allows accurate accounting for nuclear shape but exploits the clear 2D nuclear boundaries that are present in sectional slices to avoid the computational burden of fitting a complex shape model to volume data. When tested over C. elegans, Drosophila, zebrafish and mouse data, our method yielded 0 to 3.7% error, up to six times more accurate as well as being 30 times faster than published performances. We demonstrate our method's potential by reconstructing the morphogenesis of the C. elegans pharynx. This is an important and much studied developmental process that could not previously be followed at this single cell level of detail.

Conclusions
Because our approach is specialized for the characteristics of optically sectioned nuclear images, it can achieve superior accuracy in significantly less time than other approaches. Both of these characteristics are necessary for practical analysis of overwhelmingly large data sets where processing must be scalable to hundreds of thousands of cells and where the time cost of manual error correction makes it impossible to use data with high error rates. Our approach is fast, accurate, available as open source software and its learned shape model is easy to retrain. As our pharynx development example shows, these characteristics make single cell analysis relatively easy and will enable novel experimental methods utilizing complex data sets.
Signatures of selection in loci governing major colour patterns in Heliconius butterflies and related species
Authors: Wu Grace C , Joron Mathieu , Jiggins Chris D 
Published: November 2010

Abstract

Background
Protein-coding change is one possible genetic mechanism underlying the evolution of adaptive wing colour pattern variation in Heliconius butterflies. Here we determine whether 38 putative genes within two major Heliconius patterning loci, HmYb and HmB, show evidence of positive selection. Ratios of nonsynonymous to synonymous nucleotide changes (ω) were used to test for selection, as a means of identifying candidate genes within each locus that control wing pattern.

Results
Preliminary analyses using 454 transcriptome and Bacterial Artificial Chromosome (BAC) sequences from three Heliconius species highlighted a cluster of genes within each region showing relatively higher rates of sequence evolution. Other genes within the region appear to be highly constrained, and no ω estimates exceeded one. Three genes from each locus with the highest average pairwise ω values were amplified from additional Heliconius species and races. Two selected genes, fizzy-like (HmYb) and DALR (HmB), were too divergent for amplification across species and were excluded from further analysis. Amongst the remaining genes, HM00021 and Kinesin possessed the highest background ω values within the HmYb and HmB loci, respectively. After accounting for recombination, these two genes both showed evidence of having codons with a signature of selection, although statistical support for this signal was not strong in any case.

Conclusions
Tests of selection reveal a cluster of candidate genes in each locus, suggesting that weak directional selection may be occurring within a small region of each locus, but coding changes alone are unlikely to explain the full range of wing pattern diversity. These analyses pinpoint many of the same genes believed to be involved in the control of colour patterning in Heliconius that have been identified through other studies implementing different research methods.
Novel intron markers to study the phylogeny of closely related mammalian species
Authors: Igea Javier , Juste Javier , Castresana Jose 
Published: November 2010

Abstract

Background
Multilocus phylogenies can be used to infer the species tree of a group of closely related species. In species trees, the nodes represent the actual separation between species, thus providing essential information about their evolutionary history. In addition, multilocus phylogenies can help in analyses of species delimitation, gene flow and genetic differentiation within species. However, few adequate markers are available for such studies.

Results
In order to develop nuclear markers that can be useful in multilocus studies of mammals, we analyzed the mammalian genomes of human, chimpanzee, macaque, dog and cow. Rodents were excluded due to their unusual genomic features. Introns were extracted from the mammalian genomes because of their greater genetic variability and ease of amplification from the flanking exons. To an initial set of more than 10,000 one-to-one orthologous introns we applied several filters to select introns that belong to single-copy genes, show neutral evolutionary rates and have an adequate length for their amplification. This analysis led to a final list of 224 intron markers randomly distributed along the genome. To experimentally test their validity, we amplified twelve of these introns in a panel of six mammalian species. The result was that seven of these introns gave rise to a PCR band of the expected size in all species. In addition, we sequenced these bands and analyzed the accumulation of substitutions in these introns in five pairs of closely related species. The results showed that the estimated genetic distances in the five species pairs was quite variable among introns and that this divergence cannot be directly predicted from the overall intron divergence in mammals.

Conclusions
We have designed a new set of 224 nuclear introns with optimal features for the phylogeny of closely related mammalian species. A large proportion of the introns tested experimentally showed a perfect amplification and enough variability in most species, indicating that this marker set can be very helpful in multilocus phylogenetics of mammals. Due to the lower variability and stronger stochasticity of nuclear markers with respect to mitochondrial genes, studies should be designed to make use of several markers like the ones designed here.
Bacillus cereus cytotoxins Hbl, Nhe and CytK are secreted via the Sec translocation pathway
Authors: Fagerlund Annette , Lindbäck Toril , Granum Per Einar 
Published: November 2010

Abstract

Background

Bacillus cereus and the closely related Bacillus thuringiensis are Gram positive opportunistic pathogens that may cause food poisoning, and the three secreted pore-forming cytotoxins Hbl, Nhe and CytK have been implicated as the causative agents of diarrhoeal disease. It has been proposed that the Hbl toxin is secreted using the flagellar export apparatus (FEA) despite the presence of Sec-type signal peptides. As protein secretion is of key importance in virulence of a microorganism, the mechanisms by which these toxins are secreted were further investigated.

Results
Sec-type signal peptides were identified in all toxin components, and secretion of Hbl component B was shown to be dependent on an intact Sec-type signal peptide sequence. Further indication that secretion of Hbl, Nhe and CytK is dependent on the Sec translocation pathway, the main pathway on which bacterial secretion relies, was suggested by the observed intracellular accumulation and reduced secretion of the toxins in cultures supplemented with the SecA inhibitor sodium azide. Although a FEA deficient strain (a flhA mutant) showed reduced toxin expression and reduced cytotoxicity, it readily secreted overexpressed Hbl B, showing that the FEA is not required for Hbl secretion. Thus, the concurrent lack of flagella and reduced toxin secretion in the FEA deficient strain may point towards the presence of a regulatory link between motility and virulence genes, rather than FEA-dependent toxin secretion.

Conclusions
The Hbl, Nhe and CytK toxins appear to be secreted using the Sec pathway, and the reduced Hbl expression of a FEA deficient strain was shown not to be due to a secretion defect.
Ampicillin/Sulbactam versus Cefuroxime as antimicrobial prophylaxis for cesarean delivery: a randomized study
Authors: Ziogos Eleftherios , Tsiodras Sotirios , Matalliotakis Ioannis , Giamarellou Helen , Kanellakopoulou Kyriaki 
Published: November 2010

Abstract

Background
The efficacy and safety of a single dose of ampicillin/sulbactam compared to a single dose of cefuroxime at cord clamp for prevention of post-cesarean infectious morbidity has not been assessed.

Methods
Women scheduled for cesarean delivery were randomized to receive a single dose of either 3 g of ampicillin-sulbactam or 1.5 g of cefuroxime intravenously, after umbilical cord clamping. An evaluation for development of postoperative infections and risk factor analysis was performed.

Results
One hundred and seventy-six patients (median age 28 yrs, IQR: 24-32) were enrolled in the study during the period July 2004 - July 2005. Eighty-five (48.3%) received cefuroxime prophylaxis and 91 (51.7%) ampicillin/sulbactam. Postoperative infection developed in 5 of 86 (5.9%) patients that received cefuroxime compared to 8 of 91 (8.8%) patients that received ampicillin/sulbactam (p = 0.6). In univariate analyses 6 or more vaginal examinations prior to the operation (p = 0.004), membrane rupture for more than 6 hours (p = 0.08) and blood loss greater than 500 ml (p = 0.018) were associated with developing a postoperative surgical site infection (SSI). In logistic regression having 6 or more vaginal examinations was the most significant risk factor for a postoperative SSI (OR 6.8, 95% CI: 1.4-33.4, p = 0.019). Regular prenatal follow-up was associated with a protective effect (OR 0.04, 95% CI: 0.005-0.36, p = 0.004).

Conclusions
Ampicillin/sulbactam was as safe and effective as cefuroxime when administered for the prevention of infections following cesarean delivery.

Trial registration
Clinicaltrials.gov identifier: NCT01138852
Genetic variants in the TIRAP gene are associated with increased risk of sepsis-associated acute lung injury
Authors: Song Zhenju , Tong Chaoyang , Sun Zhan , Shen Yao , Yao Chenling , Jiang Jinjun , Yin Jun , Gao Lei , Song Yuanlin , Bai Chunxue 
Published: November 2010

Abstract

Background
Toll like receptors (TLRs) signaling pathways, including the adaptor protein Mal encoded by the TIRAP gene, play a central role in the development of acute lung injury (ALI). Recently, the TIRAP variants have been described association with susceptibility to inflammatory diseases. The aim of this study was to investigate whether genetic variants in TIRAP are associated with the development of ALI.

Methods
A case-control collection from Han Chinese of 298 healthy subjects, 278 sepsis-associated ALI and 288 sepsis alone patients were included. Three tag single nucleotide polymorphisms (SNPs) of the TIRAP gene and two additional SNPs that have previously showed association with susceptibility to other inflammatory diseases were genotyped by direct sequencing. The differences of allele, genotype and haplotype frequencies were evaluated between three groups.

Results
The minor allele frequencies of both rs595209 and rs8177375 were significantly increased in ALI patients compared with both healthy subjects (odds ratio (OR) = 1.47, 95% confidence interval (CI):1.15-1.88, P = 0.0027 and OR = 1.97, 95% CI: (1.38-2.80), P = 0.0001, respectively) and sepsis alone patients (OR = 1.44, 95% CI: 1.12-1.85, P = 0.0041 and OR = 1.82, 95% CI: 1.28-2.57, P = 0.00079, respectively). Haplotype consisting of these two associated SNPs strengthened the association with ALI susceptibility. The frequency of haplotype AG (rs595209A, rs8177375G) in the ALI samples was significantly higher than that in the healthy control group (OR = 2.13, 95% CI: 1.46-3.09, P = 0.00006) and the sepsis alone group (OR = 2.24, 95% CI: 1.52-3.29, P = 0.00003). Carriers of the haplotype CA (rs595209C, rs8177375A) had a lower risk for ALI compared with healthy control group (OR = 0.69, 95% CI: 0.54-0.88, P = 0.0003) and sepsis alone group (OR = 0.71, 95% CI: 0.55-0.91, P = 0.0006). These associations remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons.

Conclusions
These results indicated that genetic variants in the TIRAP gene might be associated with susceptibility to sepsis-associated ALI in Han Chinese population. However, the association needs to be replicated in independent studies.
Focused ultrasound-mediated bbb disruption is associated with an increase in activation of AKT: experimental study in rats
Authors: Jalali Shahrzad , Huang Yuexi , Dumont Daniel J , Hynynen Kullervo 
Published: December 2010

Abstract

Background
The Blood Brain Barrier (BBB) maintains the homeostasis of central nervous system by preventing the free passage of macromolecules from the systemic circulation into the brain. This normal physiological function of the BBB presents a challenge for delivery of therapeutic compounds into the brain. Recent studies have shown that the application of focused ultrasound together with ultrasound contrast agent (microbubbles) temporarily increases the permeability of the BBB. This effect is associated with breakdown of tight junctions, the structures that regulate the paracellular permeability of the endothelial cell layer. The influence of this ultrasound effect on the activation of intracellular signaling proteins is currently not well understood. Therefore, the aim of this study was to investigate the activation of cell survival signaling molecules in response to ultrasound-mediated BBB opening;

Methods
The BBB was disrupted in two four-spot lines (1-1.5 mm spacing) along the right hemisphere of rat brain with ultrasound beams (0.3 MPa, 120 s, 10 ms bursts, repetition frequency = 1 Hz) in the presence Definity microbubbles. Contrast-enhanced MRI images were acquired to assess the extent of BBB opening upon which the animals were sacrificed and the brains removed and processed for biochemical and immunohistochemical analyses;

Results
Immunoblotting of sonicated brain lysates resolved by SDS-PAGE demonstrated an increase in phosphorylation of Akt and its downstream signaling molecule, GSK3β, while the phosphorylation of MAPK remained unchanged. The elevated levels of pAkt and pGSK3β are still evident after 24 hours post-sonication, a time point where the integrity of the BBB is known to be re-established. Furthermore, immunofluoresence staining localized this increase in pAkt and pGSK3β levels to neuronal cells flanking the region of the disrupted BBB;

Conclusions
Our data demonstrates that ultrasound-mediated BBB disruption causes an activation of the Akt signaling pathway in neuronal cells surrounding the disrupted BBB.
BRCA1-mutated and basal-like breast cancers have similar aCGH profiles and a high incidence of protein truncating TP53 mutations
Authors: Holstege Henne , Horlings Hugo M , Velds Arno , Langerød Anita , Børresen-Dale Anne-Lise , van de Vijver Marc J , Nederlof Petra M , Jonkers Jos 
Published: November 2010

AbstractBackgroundBasal-like breast cancers (BLBC) are aggressive breast cancers for which, so far, no targeted therapy is available because they typically lack expression of hormone receptors and HER2. Phenotypic features of BLBCs, such as clinical presentation and early age of onset, resemble those of breast tumors fromBRCA1-mutation carriers. The genomic instability ofBRCA1-mutated tumors can be effectively targeted with DNA-damaging agents and poly-(ADP-ribose) polymerase 1 (PARP1) inhibitors. Molecular similarities between BLBCs andBRCA1-mutated tumors may therefore provide predictive markers for therapeutic response of BLBCs.MethodsThere are several known molecular features characteristic forBRCA1-mutated breast tumors: 1) increased numbers of genomic aberrations, 2) a distinct pattern of genomic aberrations, 3) a high frequency ofTP53mutations and 4) a high incidence of complex, protein-truncatingTP53mutations. We compared the frequency ofTP53mutations and the pattern and amount of genomic aberrations betweenBRCA1-mutated breast tumors, BLBCs and luminal breast tumors byTP53gene sequencing and array-based comparative genomics hybridization (aCGH) analysis.ResultsWe found that the high incidence of protein truncatingTP53mutations and the pattern and amount of genomic aberrations specific for BRCA1-mutated breast tumors are also characteristic for BLBCs and different from luminal breast tumors.ConclusionsComplex, protein truncating TP53 mutations in BRCA1-mutated tumors may be a direct consequence of genomic instability caused by BRCA1 loss, therefore, the presence of these types of TP53 mutations in sporadic BLBCs might be a hallmark of BRCAness and a potential biomarker for sensitivity to PARP inhibition. Also, our data suggest that a small subset of genomic regions may be used to identify BRCA1-like BLBCs. BLBCs share molecular features that were previously found to be specific for BRCA1-mutated breast tumors. These features might be useful for the identification of tumors with increased sensitivity to (high-dose or dose-dense) alkylating agents and PARP inhibitors.
Tissue-specific human beta-defensins (HBD)1, HBD2, and HBD3 secretion from human extra-placental membranes stimulated with Escherichia coli
Authors: Garcia-Lopez Guadalupe , Flores-Espinosa Pilar , Zaga-Clavellina Veronica 
Published: December 2010

AbstractBackgroundDuring an ascending infection along the reproductive tract, the extra-placental membranes must act as a selective and competent barrier against pathogens. Human beta defensins (HBD)1, HBD2, and HBD3 are key elements of innate immunity that are secreted to neutralize/control the progression of infection.MethodsFull-thickness membranes were mounted on a Transwell device, constituted by two independent chambers, 1 × 10(6) CFU/ml ofEscherichia coliwere added to either the amnion (AMN) or the choriodecidual (CHD) face or to both. Secretion profiles of HBD1, HBD2, and HBD3 to the culture medium were quantified by ELISA.ResultsIn comparison with basal conditions, the secretion profile of HBD1 remained without significant changes; HBD2 level in CHD and AMN increased 1.9- and 1.4-times, respectively, after stimulation with bacteria. HBD3 secretion level increased significantly (7.8 +/- 1.9 pg/micrograms) in the CHD but only if the stimulus was applied on the AMN side.ConclusionsSelective stimulation of extra-placental membranes withE. coli, results in a tissue specific secretion of HBD1, HBD2, and HBD3 mainly in the CHD, which is the first infected region during an ascending infection.
Epigenetic regulation of CD133 and tumorigenicity of CD133 positive and negative endometrial cancer cells
Authors: Friel Anne M , Zhang Ling , Curley Michael D , Therrien Vanessa A , Sergent Petra A , Belden Sarah E , Borger Darrell R , Mohapatra Gayatry , Zukerberg Lawrence R , Foster Rosemary , Rueda Bo R 
Published: December 2010

AbstractBackgroundRecent data provide significant evidence to support the hypothesis that there are sub-populations of cells within solid tumors that have an increased tumor initiating potential relative to the total tumor population. CD133, a cell surface marker expressed on primitive cells of neural, hematopoietic, endothelial and epithelial lineages has been identified as a marker for tumor initiating cells in solid tumors of the brain, colon, pancreas, ovary and endometrium. Our objectives were to assess the relative level of CD133 expressing cells in primary human endometrial tumors, confirm their tumorigenic potential, and determine whether CD133 expression was epigenetically modified.MethodsWe assessed CD133 expression in primary human endometrial tumors by flow cytometry and analyzed the relative tumorigenicity of CD133+ and CD133- cells in anin vivoNOD/SCID mouse model. We assessed potential changes in CD133 expression over the course of serial transplantation by immunofluorescence and flow cytometry. We further examined CD133 promoter methylation and expression in normal endometrium and malignant tumors.ResultsAs determined by flow cytometric analysis, the percentage of CD133+ cells in primary human endometrial cancer samples ranged from 5.7% to 27.4%. In addition, we confirmed the tumor initiating potential of CD133+ and CD133-cell fractions in NOD/SCID mice. Interestingly, the percentage of CD133+ cells in human endometrial tumor xenografts, as evidenced by immunofluorescence, increased with serial transplantation although this trend was not consistently detected by flow cytometry. We also determined that the relative levels of CD133 increased in endometrial cancer cell lines following treatment with 5-aza-2'-deoxycytidine suggesting a role for methylation in the regulation of CD133. To support this finding, we demonstrated that regions of the CD133 promoter were hypomethylated in malignant endometrial tissue relative to benign control endometrial tissue. Lastly, we determined that methylation of the CD133 promoter decreases over serial transplantation of an endometrial tumor xenograft.ConclusionsThese findings support the hypotheses that CD133 expression in endometrial cancer may be epigenetically regulated and that cell fractions enriched for CD133+ cells may well contribute to endometrial cancer tumorigenicity, pathology and recurrence.