Summit of the N=40 Island of Inversion: precision mass measurements and ab initio calculations of neutron-rich chromium isotopes

Mass measurements continue to provide invaluable information for elucidating nuclear structure and scenarios of astrophysical interest. The transition region between the $Z = 20$ and $28$ proton shell closures is particularly interesting due to the onset and evolution of nuclear deformation as nuclei become more neutron rich. This provides a critical testing ground for emerging ab-initio nuclear structure models. Here, we present high-precision mass measurements of neutron-rich chromium isotopes using the sensitive electrostatic Multiple-Reflection Time-Of-Flight Mass Spectrometer (MR-TOF-MS) at TRIUMF's Ion Trap for Atomic and Nuclear Science (TITAN) facility. Our high-precision mass measurements of $^{59, 61-63}$Cr confirm previous results, and the improved precision in measurements of $^{64-65}$Cr refine the mass surface beyond N=40. With the ab initio in-medium similarity renormalization group, we examine the trends in collectivity in chromium isotopes and give a complete picture of the N=40 island of inversion from calcium to nickel.Comment: 12 pages, 7 figure

Prediction of specificity-determining residues for small-molecule kinase inhibitors

<p>Abstract</p> <p>Background</p> <p>Designing small-molecule kinase inhibitors with desirable selectivity profiles is a major challenge in drug discovery. A high-throughput screen for inhibitors of a given kinase will typically yield many compounds that inhibit more than one kinase. A series of chemical modifications are usually required before a compound exhibits an acceptable selectivity profile. Rationalizing the selectivity profile for a small-molecule inhibitor in terms of the specificity-determining kinase residues for that molecule can be an important step toward the goal of developing selective kinase inhibitors.</p> <p>Results</p> <p>Here we describe S-Filter, a method that combines sequence and structural information to predict specificity-determining residues for a small molecule and its kinase selectivity profile. Analysis was performed on seven selective kinase inhibitors where a structural basis for selectivity is known. S-Filter correctly predicts specificity determinants that were described by independent groups. S-Filter also predicts a number of novel specificity determinants that can often be justified by further structural comparison.</p> <p>Conclusion</p> <p>S-Filter is a valuable tool for analyzing kinase selectivity profiles. The method identifies potential specificity determinants that are not readily apparent, and provokes further investigation at the structural level.</p

Understanding Streptococcus suis serotype 2 infection in pigs through a transcriptional approach

<p>Abstract</p> <p>Background</p> <p><it>Streptococcus suis </it>serotype 2 (<it>S. suis </it>2) is an important pathogen of pigs. <it>S suis 2 </it>infections have high mortality rates and are characterized by meningitis, septicemia and pneumonia. <it>S. suis </it>2 is also an emerging zoonotic agent and can infect humans that are exposed to pigs or their by-products. To increase our knowledge of the pathogenesis of meningitis, septicemia and pneumonia in pigs caused by <it>S. suis </it>2, we profiled the response of peripheral blood mononuclear cells <b>(</b>PBMC), brain and lung tissues to infection with <it>S. suis </it>2 strain SC19 using the Affymetrix Porcine Genome Array.</p> <p>Results</p> <p>A total of 3,002 differentially expressed transcripts were identified in the three tissues, including 417 unique genes in brain, 210 in lung and 213 in PBMC. These genes showed differential expression (DE) patterns on analysis by visualization and integrated discovery (DAVID). The DE genes involved in the immune response included genes related to the inflammatory response (CD163), the innate immune response (TLR2, TLR4, MYD88, TIRAP), cell adhesion (CD34, SELE, SELL, SELP, ICAM-1, ICAM-2, VCAM-1), antigen processing and presentation (MHC protein complex) and angiogenesis (VEGF), together with genes encoding cytokines (interleukins). Five selected genes were validated by qRT-PCR analysis.</p> <p>Conclusions</p> <p>We studied the response to infection with <it>S. suis </it>2 strain SC19 by microarray analysis. Our findings confirmed some genes identified in previous studies and discovered numerous additional genes that potentially function in <it>S. suis </it>2 infections in vivo. This new information will form the foundation of future investigations into the pathogenesis of <it>S. suis</it>.</p

Statistical method on nonrandom clustering with application to somatic mutations in cancer

<p>Abstract</p> <p>Background</p> <p>Human cancer is caused by the accumulation of tumor-specific mutations in oncogenes and tumor suppressors that confer a selective growth advantage to cells. As a consequence of genomic instability and high levels of proliferation, many passenger mutations that do not contribute to the cancer phenotype arise alongside mutations that drive oncogenesis. While several approaches have been developed to separate driver mutations from passengers, few approaches can specifically identify activating driver mutations in oncogenes, which are more amenable for pharmacological intervention.</p> <p>Results</p> <p>We propose a new statistical method for detecting activating mutations in cancer by identifying nonrandom clusters of amino acid mutations in protein sequences. A probability model is derived using order statistics assuming that the location of amino acid mutations on a protein follows a uniform distribution. Our statistical measure is the differences between pair-wise order statistics, which is equivalent to the size of an amino acid mutation cluster, and the probabilities are derived from exact and approximate distributions of the statistical measure. Using data in the Catalog of Somatic Mutations in Cancer (COSMIC) database, we have demonstrated that our method detects well-known clusters of activating mutations in KRAS, BRAF, PI3K, and <it>β</it>-catenin. The method can also identify new cancer targets as well as gain-of-function mutations in tumor suppressors.</p> <p>Conclusions</p> <p>Our proposed method is useful to discover activating driver mutations in cancer by identifying nonrandom clusters of somatic amino acid mutations in protein sequences.</p

A Comprehensive Expression Profile of MicroRNAs in Porcine Pituitary

MicroRNAs (miRNAs) are an abundant class of small RNAs that regulate expressions of most genes. miRNAs play important roles in the pituitary, the “master” endocrine organ.However, we still don't know which role miRNAs play in the development of pituitary tissue or how much they contribute to the pituitary function. By applying a combination of microarray analysis and Solexa sequencing, we detected a total of 450 miRNAs in the porcine pituitary. Verification with RT-PCR showed a high degree of confidence for the obtained data. According to the current miRBase release17.0, the detected miRNAs included 169 known porcine miRNAs, 163 conserved miRNAs not yet identified in the pig, and 12 potentially new miRNAs not yet identified in any species, three of which were revealed using Northern blot. The pituitary might contain about 80.17% miRNA types belonging to the animal. Analysis of 10 highly expressed miRNAs with the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that the enriched miRNAs were involved not only in the development of the organ but also in a variety of inter-cell and inner cell processes or pathways that are involved in the function of the organ

Charge radii and electromagnetic moments of 195-211At

Hyperfine-structure parameters and isotope shifts of At195-211 have been measured for the first time at CERN-ISOLDE, using the in-source resonance-ionization spectroscopy method. The hyperfine structures of isotopes were recorded using a triad of experimental techniques for monitoring the photo-ion current. The Multi-Reflection Time-of-Flight Mass Spectrometer, in connection with a high-resolution electron multiplier, was used as an ion-counting setup for isotopes that either were affected by strong isobaric contamination or possessed a long half-life; the ISOLDE Faraday cups were used for cases with high-intensity beams; and the Windmill decay station was used for short-lived, predominantly α-decaying nuclei. The electromagnetic moments and changes in the mean-square charge radii of the astatine nuclei have been extracted from the measured hyperfine-structure constants and isotope shifts. This was only made possible by dedicated state-of-the-art large-scale atomic computations of the electronic factors and the specific mass shift of atomic transitions in astatine that are needed for these extractions. By comparison with systematics, it was possible to assess the reliability of the results of these calculations and their ascribed uncertainties. A strong deviation in the ground-state mean-square charge radii of the lightest astatine isotopes, from the trend of the (spherical) lead isotopes, is interpreted as the result of an onset of deformation. This behavior bears a resemblance to the deviation observed in the isotonic polonium isotopes. Cases for shape coexistence have been identified in At197,199, for which a significant difference in the charge radii for ground (9/2-) and isomeric (1/2+) states has been observed

MicroRNAome of Porcine Pre- and Postnatal Development

The domestic pig is of enormous agricultural significance and valuable models for many human diseases. Information concerning the pig microRNAome (miRNAome) has been long overdue and elucidation of this information will permit an atlas of microRNA (miRNA) regulation functions and networks to be constructed. Here we performed a comprehensive search for porcine miRNAs on ten small RNA sequencing libraries prepared from a mixture of tissues obtained during the entire pig lifetime, from the fetal period through adulthood. The sequencing results were analyzed using mammalian miRNAs, the precursor hairpins (pre-miRNAs) and the first release of the high-coverage porcine genome assembly (Sscrofa9, April 2009) and the available expressed sequence tag (EST) sequences. Our results extend the repertoire of pig miRNAome to 867 pre-miRNAs (623 with genomic coordinates) encoding for 1,004 miRNAs, of which 777 are unique. We preformed real-time quantitative PCR (q-PCR) experiments for selected 30 miRNAs in 47 tissue-specific samples and found agreement between the sequencing and q-PCR data. This broad survey provides detailed information about multiple variants of mature sequences, precursors, chromosomal organization, development-specific expression, and conservation patterns. Our data mining produced a broad view of the pig miRNAome, consisting of miRNAs and isomiRs and a wealth of information of pig miRNA characteristics. These results are prelude to the advancement in pig biology as well the use of pigs as model organism for human biological and biomedical studies

The Magnitude and Kinetics of the Mucosal HIV-Specific CD8+ T Lymphocyte Response and Virus RNA Load in Breast Milk

BACKGROUND: The risk of postnatal HIV transmission is associated with the magnitude of the milk virus load. While HIV-specific cellular immune responses control systemic virus load and are detectable in milk, the contribution of these responses to the control of virus load in milk is unknown. METHODS: We assessed the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+ T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian women throughout the period of lactation and correlated this response to milk virus RNA load and markers of breast inflammation. RESULTS: The magnitude and kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood and milk of the right and left breast, indicating independent regulation of these responses in each breast. However, there was no correlation between the magnitude of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load. Further, there was no correlation between the magnitude of this response and markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific CD8+ T lymphocyte response in milk does not appear to be solely determined by the milk virus RNA load and is likely only one of the factors contributing to maintenance of low virus load in milk