A resampling-based meta-analysis for detection of differential gene expression in breast cancer

<p>Abstract</p> <p>Background</p> <p>Accuracy in the diagnosis of breast cancer and classification of cancer subtypes has improved over the years with the development of well-established immunohistopathological criteria. More recently, diagnostic gene-sets at the mRNA expression level have been tested as better predictors of disease state. However, breast cancer is heterogeneous in nature; thus extraction of differentially expressed gene-sets that stably distinguish normal tissue from various pathologies poses challenges. Meta-analysis of high-throughput expression data using a collection of statistical methodologies leads to the identification of robust tumor gene expression signatures.</p> <p>Methods</p> <p>A resampling-based meta-analysis strategy, which involves the use of resampling and application of distribution statistics in combination to assess the degree of significance in differential expression between sample classes, was developed. Two independent microarray datasets that contain normal breast, invasive ductal carcinoma (IDC), and invasive lobular carcinoma (ILC) samples were used for the meta-analysis. Expression of the genes, selected from the gene list for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes were tested on 10 independent primary IDC samples and matched non-tumor controls by real-time qRT-PCR. Other existing breast cancer microarray datasets were used in support of the resampling-based meta-analysis.</p> <p>Results</p> <p>The two independent microarray studies were found to be comparable, although differing in their experimental methodologies (Pearson correlation coefficient, R = 0.9389 and R = 0.8465 for ductal and lobular samples, respectively). The resampling-based meta-analysis has led to the identification of a highly stable set of genes for classification of normal breast samples and breast tumors encompassing both the ILC and IDC subtypes. The expression results of the selected genes obtained through real-time qRT-PCR supported the meta-analysis results.</p> <p>Conclusion</p> <p>The proposed meta-analysis approach has the ability to detect a set of differentially expressed genes with the least amount of within-group variability, thus providing highly stable gene lists for class prediction. Increased statistical power and stringent filtering criteria used in the present study also make identification of novel candidate genes possible and may provide further insight to improve our understanding of breast cancer development.</p

siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy

Autophagy is a vital response to nutrient starvation. Here, we screened a kinase-specific siRNA library using an autophagy assay in human embryonic kidney 293 cells that measures lipidation of the marker protein GFP-LC3 following amino acid starvation. This screen identified ULK1 in addition to other novel candidates that could be confirmed with multiple siRNAs. Knockdown of ULK1, but not the related kinase ULK2, inhibited the autophagic response. Also, ULK1 knockdown inhibited rapamycin-induced autophagy consistent with a role downstream of mTOR. Overexpression of ULK1 inhibited autophagy and this inhibition was independent of its kinase activity. Deletion of the PDZ domain-binding Val-Tyr-Ala motif at the ULK1 C terminus generated a more potent dominant-negative protein. Further deletions revealed that the minimal ULK1 dominant-negative region could be mapped to residues 1-351. Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive, and this localization required the conserved C-terminal domain. In contrast, ULK1-(1-351) was diffuse in the cytoplasm. These experiments reveal at least two domains in ULK1 which likely function via unique sets of effectors to regulate autophagy

Preparation and characterisation of thiol functionalised p-tert-butylcalix[4]arene-embedded polymer inclusion membranes: performance and selectivity

Sayin, Serkan/0000-0003-0518-3208; Kir, Esengul/0000-0002-6641-3444WOS: 000471447100001Here in we report the syntheses of the thiol functionalised p-tert-butylcalix[4]arene from the reaction of p-tert-butylcalix[4]arene-dialkylbromide derivative with thiourea. The structure of the thiol functionalised p-tert-butylcalix[4]arene was determined by using (HNMR)-H-1, (CNMR)-C-13 and elemental analysis techniques. Furthermore, the thiol functionalised p-tert-butylcalix[4]arene, cellulose triacetate (CTA) and 2-nitrophenyl octyl ether (o-NPPE) in dichloromethane were used to make a new calixarene-embedded polymer inclusion membrane (Bu-t-C@PIM). The surface and structure morphology of Bu-t-C@PIM was detected using thermogravimetric analysis, elemental analysis techniques and scanning electron microscopy. The affinity (the percentage of metal ion transferred from the source solution) of a PIM towards a range of divalent cations was found to follow the order Pb2+ > Zn2+ > Ni2+ > Cu2+ > Cd2+ > Co2+. The results also indicated that the transport efficiency of Bu-t-C@PIM was repeatable and may be beneficial in the development of a simplistic and highly influential trace metal recovery method from aqueous solution.Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [215Z570]This work was supported by the Scientific and Technological Research Council of Turkey [215Z570]

RISK FACTORS OF INTRAVENOUS IMMUNOGLOBULIN RESISTANCE AND CORONARY ARTERIAL LESIONS IN TURKISH CHILDREN WITH KAWASAKI DISEASE

Kawasaki disease (KD) is the most common cause of childhood coronary artery disease. The incidence of coronary artery lesions (CALs) has declined with the routine use of intravenous immunoglobulin (IVIG) treatment, but there is still considerable risk for resistance to IVIG treatment and development of CALs. The present study was aimed to determine the risk factors in Turkish children with IVIG resistant KD and coronary artery involvement. Clinical, laboratory and echocardiographic data were retrospectively analyzed in 94 Kawasaki patients. IVIG resistant and responsive groups were compared. The IVIG resistant group had a higher rate of CALs compared to the IVIG responsive group (p= 9.5 days, C-reactive protein (CRP) >= 88 mg/L and Neutrophil/lymphocyte ratio (NLR) >= 1.69 were the best cutoff values for predicting IVIG resistance before treatment. The criteria for at least two of these three predictors were considered to be statistically significant risk factors for detecting IVIG resistance in KD before treatment (76.47% sensitivity, 71.05% specificity and 95% CI were 50.1-93.19% and 59.51-80.89%, respectively). Based on the clinical and laboratory features, we established a new risk-scoring system for predicting IVIG resistance in a cohort of Turkish children with KD. This may be useful for choosing optimal treatment for KD to prevent coronary artery involvement

Medical control of intraocular pressure after phacoemulsification

Purpose: To compare the effectiveness of oral acetazolamide, topical brinzolamide 1%, and no ocular hypotensive medication after phacoemulsification. Setting: Adnan Menderes University Department of Ophthalmology, Aydin, Turkey

Does Familial Mediterranean Fever Provoke Atherosclerosis in Children? Evaluation of Arterial Stiffness and Serum Endocan Levels

Objectives This study aimed to evaluate the risk for atherosclerosis by using echocardiographic arterial stiffness (AS) parameters and serum endocan levels, as a biomarker of endothelial dysfunction (ED) in children with FMF

Prevalence of factor V Leiden in patients with retinal vein occlusion

Purpose: Factor V Leiden mutation is a common genetic defect associated with a tendency to venous thrombosis. The aim of this study was to evaluate the prevalence of factor V Leiden in patients with retinal vein occlusion (RVO)