Toro Times: Raising Our Voices!

During the Spring 2019 semester, Dr. Noah Asher Golden\u27s Teaching of Writing K-12 students partnered with the Journalism class at Yorba Academy for the Arts. Through collaboration over a four-month period, Chapman\u27s future teachers and Yorba\u27s junior high journalists engaged a deep writing process to write a series of features, editorials, and news articles related to a number of global issues. Thank you to Principal Preciado-Martin, former principal Tracy Knibb, Mrs. Andrea Lopez, Mrs. Kori Shelton, and the Lloyd E. and Elisabeth H. Klein Family Foundation for supporting this project.https://digitalcommons.chapman.edu/yorba-chapman/1004/thumbnail.jp

Integration of sequence data from a consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2×10-6). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. © 2014 Plenge et al

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Low-Dose and In-Painting Methods for (Near) Atomic Resolution STEM Imaging of Metal Organic Frameworks (MOFs)

Metal-organic Frameworks (MOFs) are a group of crystalline and highly porous materials consisting of inorganic metal ions/clusters (nodes) that are coordinated by organic linkers. The ability to create a wide range of porous structures, where the pore size can be easily changed in size and shape offers the potential for many applications in gas storage/separation and catalysis. The presence of the organic linkers or “struts” in the sample creates challenges for high resolution microscopy as the sample itself is very sensitive to beam damage. A key challenge for understanding the structures of MOFs and how the applications can be modified by doping the nodes and changing the nature of the organic linkers, is therefore to be able to image the samples on the sub-nm length scale (the nodes are ~1 nm). The study of organics, where large single crystals with long-range order cannot be synthesized, is usually performed by either electron crystallography or direct imaging in the (scanning) transmission electron microscope (S/TEM). In the (S)TEM, large single crystals are not needed as the electron beam can be focused to a very small area (sub-nm if needed). The downside to this ability to see small areas is that because the electron beam has a strong interaction with the sample, it can cause significant levels of electron beam damage. However, the last 40 years of protein crystallography and more recently the use of in-situ liquid stages to study chemical reactions in the (S)TEM, have shown that this beam damage effect can in most cases be mitigated by the use of extremely low-dose imaging (a dose rate of less than 0.1 electrons/angstrom2/s and a cumulative dose of less than 10 electrons/angstrom2). In addition to simply lowering the dose through conventional means (changing the emission current and probe dwell time), more recent use of compressive sensing/in-painting methods for STEM has also been shown to lower the effective dose and dose rate

Methane Oxidation to Methanol Catalyzed by Cu-Oxo Clusters Stabilized in NU-1000 Metal–Organic Framework

Copper oxide clusters synthesized via atomic layer deposition on the nodes of the metal–organic framework (MOF) NU-1000 are active for oxidation of methane to methanol under mild reaction conditions. Analysis of chemical reactivity, in situ X-ray absorption spectroscopy, and density functional theory calculations are used to determine structure/activity relations in the Cu-NU-1000 catalytic system. The Cu-loaded MOF contained Cu-oxo clusters of a few Cu atoms. The Cu was present under ambient conditions as a mixture of ∼15% Cu⁺ and ∼85% Cu²⁺. The oxidation of methane on Cu-NU-1000 was accompanied by the reduction of 9% of the Cu in the catalyst from Cu²⁺ to Cu⁺. The products, methanol, dimethyl ether, and CO₂, were desorbed with the passage of 10% water/He at 135 °C, giving a carbon selectivity for methane to methanol of 45–60%. Cu oxo clusters stabilized in NU-1000 provide an active, first generation MOF-based, selective methane oxidation catalyst

Bridging Zirconia Nodes within a Metal–Organic Framework via Catalytic Ni-Hydroxo Clusters to Form Heterobimetallic Nanowires

Metal–organic frameworks (MOFs), with their well-ordered pore networks and tunable surface chemistries, offer a versatile platform for preparing well-defined nanostructures wherein functionality such as catalysis can be incorporated. Notably, atomic layer deposition (ALD) in MOFs has recently emerged as a versatile approach to functionalize MOF surfaces with a wide variety of catalytic metal-oxo species. Understanding the structure of newly deposited species and how they are tethered within the MOF is critical to understanding how these components couple to govern the active material properties. By combining local and long-range structure probes, including X-ray absorption spectroscopy, pair distribution function analysis, and difference envelope density analysis, with electron microscopy imaging and computational modeling, we resolve the precise atomic structure of metal-oxo species deposited in the MOF NU-1000 through ALD. These analyses demonstrate that deposition of NiO_<i>x</i>H_<i>y</i> clusters occurs selectively within the smallest pores of NU-1000, between the zirconia nodes, serving to connect these nodes along the <i>c</i>-direction to yield heterobimetallic metal-oxo nanowires. This bridging motif perturbs the NU-1000 framework structure, drawing the zirconia nodes closer together, and also underlies the sintering resistance of these clusters during the hydrogenation of light olefins

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that -80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAFPeer reviewe

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research