GIVE: portable genome browsers for personal websites.

Growing popularity and diversity of genomic data demand portable and versatile genome browsers. Here, we present an open source programming library called GIVE that facilitates the creation of personalized genome browsers without requiring a system administrator. By inserting HTML tags, one can add to a personal webpage interactive visualization of multiple types of genomics data, including genome annotation, "linear" quantitative data, and genome interaction data. GIVE includes a graphical interface called HUG (HTML Universal Generator) that automatically generates HTML code for displaying user chosen data, which can be copy-pasted into user's personal website or saved and shared with collaborators. GIVE is available at: https://www.givengine.org/

A ruthenium(II) hydride carbonyl complex with 4-phenylpyrimidine as co-ligand

The reaction of [RuHCl(CO)(PPh3)3] with 4-phenylpyrimidine gave a new ruthenium(II) complex, namely [RuHCl(CO)(PPh3)2(pyrim-4-Ph)]. The complex has been studied by IR and UV–vis spectroscopy and by X-ray crystallography. The molecular orbitals of the complex have been calculated by density functional theory. The spin-allowed singlet–singlet electronic transitions of the complex have been calculated by time-dependent DFT, and the UV–vis spectrum of the compound has been discussed on this basis. The emission properties of the complex were also studied

The Transient Receptor Potential Ion Channel TRPV6 Is Expressed at Low Levels in Osteoblasts and Has Little Role in Osteoblast Calcium Uptake

Background: TRPV6 ion channels are key mediators of regulated transepithelial absorption of Ca2+ within the small intestine. Trpv6-/- mice were reported to have lower bone density than wild-type littermates and significant disturbances in calcium homeostasis that suggested a role for TRPV6 in osteoblasts during bone formation and mineralization. TRPV6 and molecules related to transepithelial Ca2+ transport have been reported to be expressed at high levels in human and mouse osteoblasts. Results: Transmembrane ion currents in whole cell patch clamped SaOS-2 osteoblasts did not show sensitivity to ruthenium red, an inhibitor of TRPV5/6 ion channels, and 45Ca uptake was not significantly affected by ruthenium red in either SaOS-2 (P = 0.77) or TE-85 (P = 0.69) osteoblastic cells. In contrast, ion currents and 45Ca uptake were both significantly affected in a human bronchial epithelial cell line known to express TRPV6. TRPV6 was expressed at lower levels in osteoblastic cells than has been reported in some literature. In SaOS-2 TRPV6 mRNA was below the assay detection limit; in TE-85 TRPV6 mRNA was detected at 6.90±1.9 × 10−5 relative to B2M. In contrast, TRPV6 was detected at 7.7±3.0 × 10−2 and 2.38±0.28 × 10−4 the level of B2M in human carcinoma-derived cell lines LNCaP and CaCO-2 respectively. In murine primary calvarial osteoblasts TRPV6 was detected at 3.80±0.24 × 10−5 relative to GAPDH, in contrast with 4.3±1.5 × 10−2 relative to GAPDH in murine duodenum. By immunohistochemistry, TRPV6 was expressed mainly in myleocytic cells of the murine bone marrow and was observed only at low levels in murine osteoblasts, osteocytes or growth plate cartilage. Conclusions: TRPV6 is expressed only at low levels in osteoblasts and plays little functional role in osteoblastic calcium uptake

Membrane Sealant Poloxamer P188 Protects Against Isoproterenol Induced Cardiomyopathy in Dystrophin Deficient Mice

<p>Abstract</p> <p>Background</p> <p>Cardiomyopathy in Duchenne muscular dystrophy (DMD) is an increasing cause of death in patients. The absence of dystrophin leads to loss of membrane integrity, cell death and fibrosis in cardiac muscle. Treatment of cardiomyocyte membrane instability could help prevent cardiomyopathy.</p> <p>Methods</p> <p>Three month old female mdx mice were exposed to the β₁receptor agonist isoproterenol subcutaneously and treated with the non-ionic tri-block copolymer Poloxamer P188 (P188) (460 mg/kg/dose i.p. daily). Cardiac function was assessed using high frequency echocardiography. Tissue was evaluated with Evans Blue Dye (EBD) and picrosirius red staining.</p> <p>Results</p> <p>BL10 control mice tolerated 30 mg/kg/day of isoproterenol for 4 weeks while death occurred in mdx mice at 30, 15, 10, 5 and 1 mg/kg/day within 24 hours. Mdx mice tolerated a low dose of 0.5 mg/kg/day. Isoproterenol exposed mdx mice showed significantly increased heart rates (p < 0.02) and cardiac fibrosis (p < 0.01) over 4 weeks compared to unexposed controls. P188 treatment of mdx mice significantly increased heart rate (median 593 vs. 667 bpm; p < 0.001) after 2 weeks and prevented a decrease in cardiac function in isoproterenol exposed mice (Shortening Fraction = 46 ± 6% vs. 35 ± 6%; p = 0.007) after 4 weeks. P188 treated mdx mice did not show significant differences in cardiac fibrosis, but demonstrated significantly increased EBD positive fibers.</p> <p>Conclusions</p> <p>This model suggests that chronic intermittent intraperitoneal P188 treatment can prevent isoproterenol induced cardiomyopathy in dystrophin deficient mdx mice.</p

A Search for Energy Minimized Sequences of Proteins

In this paper, we present numerical evidence that supports the notion of minimization in the sequence space of proteins for a target conformation. We use the conformations of the real proteins in the Protein Data Bank (PDB) and present computationally efficient methods to identify the sequences with minimum energy. We use edge-weighted connectivity graph for ranking the residue sites with reduced amino acid alphabet and then use continuous optimization to obtain the energy-minimizing sequences. Our methods enable the computation of a lower bound as well as a tight upper bound for the energy of a given conformation. We validate our results by using three different inter-residue energy matrices for five proteins from protein data bank (PDB), and by comparing our energy-minimizing sequences with 80 million diverse sequences that are generated based on different considerations in each case. When we submitted some of our chosen energy-minimizing sequences to Basic Local Alignment Search Tool (BLAST), we obtained some sequences from non-redundant protein sequence database that are similar to ours with an E-value of the order of 10-7. In summary, we conclude that proteins show a trend towards minimizing energy in the sequence space but do not seem to adopt the global energy-minimizing sequence. The reason for this could be either that the existing energy matrices are not able to accurately represent the inter-residue interactions in the context of the protein environment or that Nature does not push the optimization in the sequence space, once it is able to perform the function

Enhanced Discrimination of Malignant from Benign Pancreatic Disease by Measuring the CA 19-9 Antigen on Specific Protein Carriers

The CA 19-9 assay detects a carbohydrate antigen on multiple protein carriers, some of which may be preferential carriers of the antigen in cancer. We tested the hypothesis that the measurement of the CA 19-9 antigen on individual proteins could improve performance over the standard CA 19-9 assay. We used antibody arrays to measure the levels of the CA 19-9 antigen on multiple proteins in serum or plasma samples from patients with pancreatic adenocarcinoma or pancreatitis. Sample sets from three different institutions were examined, comprising 531 individual samples. The measurement of the CA 19-9 antigen on any individual protein did not improve upon the performance of the standard CA 19-9 assay (82% sensitivity at 75% specificity for early-stage cancer), owing to diversity among patients in their CA 19-9 protein carriers. However, a subset of cancer patients with no elevation in the standard CA 19-9 assay showed elevations of the CA 19-9 antigen specifically on the proteins MUC5AC or MUC16 in all sample sets. By combining measurements of the standard CA 19-9 assay with detection of CA 19-9 on MUC5AC and MUC16, the sensitivity of cancer detection was improved relative to CA 19-9 alone in each sample set, achieving 67–80% sensitivity at 98% specificity. This finding demonstrates the value of measuring glycans on specific proteins for improving biomarker performance. Diagnostic tests with improved sensitivity for detecting pancreatic cancer could have important applications for improving the treatment and management of patients suffering from this disease

Ectopic Catalase Expression in Mitochondria by Adeno-Associated Virus Enhances Exercise Performance in Mice

Oxidative stress is thought to compromise muscle contractility. However, administration of generic antioxidants has failed to convincingly improve performance during exhaustive exercise. One possible explanation may relate to the inability of the supplemented antioxidants to effectively eliminate excessive free radicals at the site of generation. Here, we tested whether delivering catalase to the mitochondria, a site of free radical production in contracting muscle, could improve treadmill performance in C57Bl/6 mice. Recombinant adeno-associated virus serotype-9 (AV.RSV.MCAT) was generated to express a mitochondria-targeted catalase gene. AV.RSV.MCAT was delivered to newborn C57Bl/6 mouse circulation at the dose of 1012 vector genome particles per mouse. Three months later, we observed a ∼2 to 10-fold increase of catalase protein and activity in skeletal muscle and the heart. Subcellular fractionation western blot and double immunofluorescence staining confirmed ectopic catalase expression in the mitochondria. Compared with untreated control mice, absolute running distance and body weight normalized running distance were significantly improved in AV.RSV.MCAT infected mice during exhaustive treadmill running. Interestingly, ex vivo contractility of the extensor digitorum longus muscle was not altered. Taken together, we have demonstrated that forced catalase expression in the mitochondria enhances exercise performance. Our result provides a framework for further elucidating the underlying mechanism. It also raises the hope of applying similar strategies to remove excessive, pathogenic free radicals in certain muscle diseases (such as Duchenne muscular dystrophy) and ameliorate muscle disease

Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Culture Shapes Efficiency of Facial Age Judgments

Background: Cultural differences in socialization can lead to characteristic differences in how we perceive the world. Consistent with this influence of differential experience, our perception of faces (e.g., preference, recognition ability) is shaped by our previous experience with different groups of individuals. Methodology/Principal Findings: Here, we examined whether cultural differences in social practices influence our perception of faces. Japanese, Chinese, and Asian-Canadian young adults made relative age judgments (i.e., which of these two faces is older?) for East Asian faces. Cross-cultural differences in the emphasis on respect for older individuals was reflected in participants ’ latency in facial age judgments for middle-age adult faces—with the Japanese young adults performing the fastest, followed by the Chinese, then the Asian-Canadians. In addition, consistent with the differential behavioural and linguistic markers used in the Japanese culture when interacting with individuals younger than oneself, only the Japanese young adults showed an advantage in judging the relative age of children’s faces. Conclusions/Significance: Our results show that different sociocultural practices shape our efficiency in processing facia

Genetic and epigenetic silencing of the beclin 1 gene in sporadic breast tumors

<p>Abstract</p> <p>Background</p> <p>Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. <it>Beclin 1 </it>mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of <it>beclin 1 </it>gene was frequently observed in breast tumors, whether there was other regulatory mechanism of <it>beclin 1 </it>was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors.</p> <p>Methods</p> <p>20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs) were collected. The mRNA expression of <it>beclin 1 </it>was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH) was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island.</p> <p>Results</p> <p>Decreased <it>beclin 1 </it>mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of <it>beclin 1 </it>mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the <it>beclin 1 </it>gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression.</p> <p>Conclusions</p> <p>These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of <it>beclin 1 </it>in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer.</p