Resampling methods to reduce the selection bias in genetic effect estimation in genome-wide scans

Using the simulated data of Problem 2 for Genetic Analysis Workshop 14 (GAW14), we investigated the ability of three bootstrap-based resampling estimators (a shrinkage, an out-of-sample, and a weighted estimator) to reduce the selection bias for genetic effect estimation in genome-wide linkage scans. For the given marker density in the preliminary genome scans (7 cM for microsatellite and 3 cM for SNP), we found that the two sets of markers produce comparable results in terms of power to detect linkage, localization accuracy, and magnitude of test statistic at the peak location. At the locations detected in the scan, application of the three bootstrap-based estimators substantially reduced the upward selection bias in genetic effect estimation for both true and false positives. The relative effectiveness of the estimators depended on the true genetic effect size and the inherent power to detect it. The shrinkage estimator is recommended when the power to detect the disease locus is low. Otherwise, the weighted estimator is recommended

Comparison of family-based association tests in chromosome regions selected by linkage-based confidence intervals

We use the Genetic Analysis Workshop 14 simulated data to explore the effectiveness of a two-stage strategy for mapping complex disease loci consisting of an initial genome scan with confidence interval construction for gene location, followed by fine mapping with family-based tests of association on a dense set of single-nucleotide polymorphisms. We considered four types of intervals: the 1-LOD interval, a basic percentile bootstrap confidence interval based on the position of the maximum Zlr score, and asymptotic and bootstrap confidence intervals based on a generalized estimating equations method. For fine mapping we considered two family-based tests of association: a test based on a likelihood ratio statistic and a transmission-disequilibrium-type test implemented in the software FBAT. In two of the simulation replicates, we found that the bootstrap confidence intervals based on the peak Zlr and the 1-LOD support interval always contained the true disease loci and that the likelihood ratio test provided further strong confirmatory evidence of the presence of disease loci in these regions

Gastrojejunocolic fistula after gastrojejunostomy: a case series

<p>Abstract</p> <p>Introduction</p> <p>Gastrojejunocolic (GJC) fistulae represent a significant post-surgical cause of morbidity and mortality. GJC fistulae represent rare post-surgical complications, and most are associated with gastric surgery. In the past, this complication has been under-recognized because a fistula may form years after surgery.</p> <p>Case presentation</p> <p>We describe two cases of gastrojejunocolic fistula in men aged 67 and 60 who both initially presented with watery diarrhea and weight loss. Upper GI studies with small bowel follow-through or barium contrast enema studies allowed a conclusive diagnosis to be made. Both patients underwent one-stage en bloc resection, and their postoperative course was uneventful.</p> <p>Conclusion</p> <p>With surgery, this condition is entirely correctable. Pre-operative nutritional status should be evaluated in patients undergoing corrective surgery, and total parenteral nutrition plays a major role in the provision of bowel rest to allow recovery in malnourished patients.</p

Automatically extracting functionally equivalent proteins from SwissProt

In summary, FOSTA provides an automated analysis of annotations in UniProtKB/Swiss-Prot to enable groups of proteins already annotated as functionally equivalent, to be extracted. Our results demonstrate that the vast majority of UniProtKB/Swiss-Prot functional annotations are of high quality, and that FOSTA can interpret annotations successfully. Where FOSTA is not successful, we are able to highlight inconsistencies in UniProtKB/Swiss-Prot annotation. Most of these would have presented equal difficulties for manual interpretation of annotations. We discuss limitations and possible future extensions to FOSTA, and recommend changes to the UniProtKB/Swiss-Prot format, which would facilitate text-mining of UniProtKB/Swiss-Prot

Fe3O4–Au and Fe2O3–Au Hybrid Nanorods: Layer-by-Layer Assembly Synthesis and Their Magnetic and Optical Properties

A layer-by-layer technique has been developed to synthesize FeOOH–Au hybrid nanorods that can be transformed into Fe2O3–Au and Fe3O4–Au hybrid nanorods via controllable annealing process. The homogenous deposition of Au nanoparticles onto the surface of FeOOH nanorods can be attributed to the strong electrostatic attraction between metal ions and polyelectrolyte-modified FeOOH nanorods. The annealing atmosphere controls the phase transformation from FeOOH–Au to Fe3O4–Au and α-Fe2O3–Au. Moreover, the magnetic and optical properties of as-synthesized Fe2O3–Au and Fe3O4–Au hybrid nanorods have been investigated

Frequency and predictors of the lupus low disease activity state in a multi-national and multi-ethnic cohort

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MiR-339-5p inhibits breast cancer cell migration and invasion in vitro and may be a potential biomarker for breast cancer prognosis

<p>Abstract</p> <p>Background</p> <p>MicroRNAs (miRNAs) play an important role in the regulation of cell growth, differentiation, apoptosis, and carcinogenesis. Detection of their expression may lead to identifying novel markers for breast cancer.</p> <p>Methods</p> <p>We profiled miRNA expression in three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and then focused on one miRNA, miR-339-5p, for its role in regulation of tumor cell growth, migration, and invasion and target gene expression. We then analyzed miR-339-5p expression in benign and cancerous breast tissue specimens.</p> <p>Results</p> <p>A number of miRNAs were differentially expressed in these cancer cell lines. Real-time PCR indicated that miR-339-5p expression was downregulated in the aggressive cell lines MDA-MB-468 and MDA-MB-231 and in breast cancer tissues compared with benign tissues. Transfection of miR-339-5p oligonucleotides reduced cancer cell growth only slightly but significantly decreased tumor cell migration and invasion capacity compared with controls. Real-time PCR analysis showed that BCL-6, a potential target gene of miR-339-5p, was downregulated in MDA-MB-231 cells by miR-339-5p transfection. Furthermore, the reduced miR-339-5p expression was associated with an increase in metastasis to lymph nodes and with high clinical stages. Kaplan-Meier analyses found that the patients with miR-339-5p expression had better overall and relapse-free survivals compared with those without miR-339-5p expression. Cox proportional hazards analyses showed that miR-339-5p expression was an independent prognostic factor for breast cancer patients.</p> <p>Conclusions</p> <p>MiR-339-5p may play an important role in breast cancer progression, suggesting that miR-339-5p should be further evaluated as a biomarker for predicting the survival of breast cancer patients.</p

Immunolocalization of the short neuropeptide F receptor in queen brains and ovaries of the red imported fire ant (Solenopsis invicta Buren)

<p>Abstract</p> <p>Background</p> <p>Insect neuropeptides are involved in diverse physiological functions and can be released as neurotransmitters or neuromodulators acting within the central nervous system, and as circulating neurohormones in insect hemolymph. The insect short neuropeptide F (sNPF) peptides, related to the vertebrate neuropeptide Y (NPY) peptides, have been implicated in the regulation of food intake and body size, and play a gonadotropic role in the ovaries of some insect species. Recently the sNPF peptides were localized in the brain of larval and adult <it>Drosophila</it>. However, the location of the sNPF receptor, a G protein-coupled receptor (GPCR), has not yet been investigated in brains of any adult insect. To elucidate the sites of action of the sNPF peptide(s), the sNPF receptor tissue expression and cellular localization were analyzed in queens of the red imported fire ant, <it>Solenopsis invicta </it>Buren (Hymenoptera), an invasive social insect.</p> <p>Results</p> <p>In the queen brains and subesophageal ganglion about 164 cells distributed in distinctive cell clusters (C1-C9 and C12) or as individual cells (C10, C11) were immuno-positive for the sNPF receptor. Most of these neurons are located in or near important sensory neuropils including the mushroom bodies, the antennal lobes, the central complex, and in different parts of the protocerebrum, as well as in the subesophageal ganglion. The localization of the sNPF receptor broadly links the receptor signaling pathway with circuits regulating learning and feeding behaviors. In ovaries from mated queens, the detection of sNPF receptor signal at the posterior end of oocytes in mid-oogenesis stage suggests that the sNPF signaling pathway may regulate processes at the oocyte pole.</p> <p>Conclusions</p> <p>The analysis of sNPF receptor immunolocalization shows that the sNPF signaling cascade may be involved in diverse functions, and the sNPF peptide(s) may act in the brain as neurotransmitter(s) or neuromodulator(s), and in the ovaries as neurohormone(s). To our knowledge, this is the first report of the cellular localization of a sNPF receptor on the brain and ovaries of adult insects.</p