Genomic analysis of metabolic pathway gene expression in mice

BACKGROUND: A segregating population of (C57BL/6J × DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice. RESULTS: We integrated global gene-expression data with phenotypic and genetic segregation analyses to evaluate metabolic pathways associated with obesity. Using two approaches we identified 13 metabolic pathways whose genes are coordinately regulated in association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19 were found to control the coordinated expression of these pathways. Using criteria that included trait correlation, differential gene expression, and linkage to genomic regions, we identified novel genes potentially associated with the identified pathways. CONCLUSION: This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Location determination Algorithms for Distributed

Wireless ad-hoc networks are self-organizing, rapidly deployable and require no fixed infrastructure. Localization is defined as the ability of the sensors in a network to determine their position in the same co-ordinate system. The most prevalent technique of localization in sensor networks is use of a global positioning system (GPS).However it has the disadvantage of working only outdoors, on lands with sparse foliage environments and generally has high power consumption. Our project aims location determination or localization in Wireless Ad-Hoc sensor networks. It requires a simple average hop distance based algorithm allowing a distributed set of "dumb" nodes to determine their location by calculating their distance to known landmarks, i.e. the "smart nodes". We propose the "Distance Vector -- Hop Propagation" algorithm for localization in sensor networks

Genome-wide screening for genetic loci associated with noise-induced hearing loss

Noise-induced hearing loss (NIHL) is one of the more common sources of environmentally induced hearing loss in adults. In a mouse model, Castaneous (CAST/Ei) is an inbred strain that is resistant to NIHL, while the C57BL/6J strain is susceptible. We have used the genome-tagged mice (GTM) library of congenic strains, carrying defined segments of the CAST/Ei genome introgressed onto the C57BL/6J background, to search for loci modifying the noise-induced damage seen in the C57BL/6J strain. NIHL was induced by exposing 6-8-week old mice to 108 dB SPL intensity noise. We tested the hearing of each mouse strain up to 23 days after noise exposure using auditory brainstem response (ABR). This study identifies a number of genetic loci that modify the initial response to damaging noise, as well as long-term recovery. The data suggest that multiple alleles within the CAST/Ei genome modify the pathogenesis of NIHL and that screening congenic libraries for loci that underlie traits of interest can be easily carried out in a high-throughput fashion.</p

Assessment of the anterior segment of patients with primary congenital glaucoma using handheld optical coherence tomography.

PURPOSE: To investigate the potential of handheld optical coherence tomography (HH-OCT) in assessing the anterior segment of the eye in patients with primary congenital glaucoma. DESIGN: A prospective, case-controlled observational study. PARTICIPANTS: Twenty-two patients with primary congenital glaucoma (PCG, 9 females and 13 males; mean age 4.36 ± 3.4 years) and age-, gender- and ethnicity-matched healthy participants. METHODS: Anterior OCT was performed in all participants using a high-resolution HH SD-OCT device (Envisu 2300, Leica Microsystems, Germany) without anaesthesia or sedation. RESULTS: Anterior HH-OCT in PCG visualised Haab's striae in 14.3%, uneven internal cornea in 9.5% and epithelial thickening in 11.9% of patients with central corneal thickening (CCT, p < 0.001). CCT was significantly correlated with the intraocular pressure (IOP, p < 0.001). The flat iris with a thin collarette zone was found in 59.5%, anterior iris insertion in 11.90% of eyes affected by PCG. Two independent examiners showed sensitivity and specificity of 87% and 77%, respectively, by instating iris thinning and flattening of the anterior profile. CONCLUSIONS: Anterior HH-OCT has significant potential to improve diagnosis and management of PCG. Clinically relevant information can be obtained non-invasively and without sedation. High specificity makes anterior HH-OCT an important adjunct for management of PCG. Excellent visualisation of the iris insertion on OCT indicates potential for AS OCT to assist with surgical planning, including decision on the type of surgery and location of the incision

Prospective Evaluation of High Titer Autoantibodies and Fetal Home Monitoring in the Detection of Atrioventricular Block Among Anti-SSA/Ro Pregnancies

OBJECTIVE: This prospective study of pregnant patients, Surveillance To Prevent AV Block Likely to Occur Quickly (STOP BLOQ), addresses the impact of anti-SSA/Ro titers and utility of ambulatory monitoring in the detection of fetal second-degree atrioventricular block (AVB). METHODS: Women with anti-SSA/Ro autoantibodies by commercial testing were stratified into high and low anti-52-kD and/or 60-kD SSA/Ro titers applying at-risk thresholds defined by previous evaluation of AVB pregnancies. The high-titer group performed fetal heart rate and rhythm monitoring (FHRM) thrice daily and weekly/biweekly echocardiography from 17-26 weeks. Abnormal FHRM prompted urgent echocardiography to identify AVB. RESULTS: Anti-52-kD and/or 60-kD SSA/Ro met thresholds for monitoring in 261 of 413 participants (63%); for those, AVB frequency was 3.8%. No cases occurred with low titers. The incidence of AVB increased with higher levels, reaching 7.7% for those in the top quartile for anti-60-kD SSA/Ro, which increased to 27.3% in those with a previous child who had AVB. Based on levels from 15 participants with paired samples from both an AVB and a non-AVB pregnancy, healthy pregnancies were not explained by decreased titers. FHRM was considered abnormal in 45 of 30,920 recordings, 10 confirmed AVB by urgent echocardiogram, 7 being second-degree AVB, all \u3c12 hours from normal FHRM and within another 0.75 to 4 hours to echocardiogram. The one participant with second/third-degree and two participants with third-degree AVB were diagnosed by urgent echocardiogram \u3e17 to 72 hours from an FHRM. Surveillance echocardiograms detected no AVB when the preceding interval FHRM recordings were normal. CONCLUSION: High-titer antibodies are associated with an increased incidence of AVB. Anti-SSA/Ro titers remain stable over time and do not explain the discordant recurrence rates, suggesting that other factors are required. Fetal heart rate and rhythm (FHRM) with results confirmed by a pediatric cardiologist reliably detects conduction abnormalities, which may reduce the need for serial echocardiograms