Alterations in SAMD9, AHSG, FRG2C, and FGFR4 Genes in a Case of Late-Onset Massive Tumoral Calcinosis

Background/Objective: Tumoral calcinosis (TC) is a rare, arcane, and debilitating disorder of phosphate metabolism manifesting as hard masses in soft tissues. Primary hyperphosphatemic TC has been shown to be caused by pathogenic variants in the genes encoding FGF23, GALNT3, and KLOTHO. We report a case of massive TC mechanistically associated with phosphatonin resistance associated with heterozygous alterations in the sterile alfa motif domain–containing protein-9 gene (SAMD9), alfa 2-Heremans-Schmid glycoprotein gene (AHSG), FSHD region gene 2-family member-C gene (FRG2C), and fibroblast growth factor receptor-4 gene (FGFR4). Case Report: A middle-aged Malay woman with systemic sclerosis presented with painful hard lumps of her axillae, lower limbs, and external genitalia. She was eucalcemic with mild hyperphosphatemia associated with reduced urinary phosphate excretion. Magnetic resonance imaging revealed calcified soft tissue masses. Paradoxically, the serum intact FGF23 level increased to 89.6 pg/mL, corroborated by Western blots, which also showed overexpression of sFRP4 and MEPE, consistent with phosphatonin resistance. Discussion: Whole genome sequencing identified 2 heterozygous alterations (p.A454T and p.T479M) in SAMD9, 2 heterozygous alterations (p.M248T and p.S256T) in AHSG, a frameshift alteration (p.Arg156fs) in FRG2C, and a heterozygous alteration (p.G388R) in FGFR4, all of which are associated with calcinosis. Nonsynonymous alterations of FRP4 and MEPE were also detected. Conclusion: This highlights that the simultaneous occurrence of alterations in several genes critical in phosphate homeostasis may trigger massive TC despite their heterozygosity. These findings should prompt functional studies in cell and animal models to reveal mechanistic insights in the pathogenesis of such crippling mineralization disorders

Transcriptome-Based Exon Capture Enables Highly Cost-Effective Comparative Genomic Data Collection At Moderate Evolutionary Scales

Background: To date, exon capture has largely been restricted to species with fully sequenced genomes, which has precluded its application to lineages that lack high quality genomic resources. We developed a novel strategy for designing array-based exon capture in chipmunks (Tamias) based on de novo transcriptome assemblies. We evaluated the performance of our approach across specimens from four chipmunk species. Results: We selectively targeted 11,975 exons (similar to 4 Mb) on custom capture arrays, and enriched over 99% of the targets in all libraries. The percentage of aligned reads was highly consistent (24.4-29.1%) across all specimens, including in multiplexing up to 20 barcoded individuals on a single array. Base coverage among specimens and within targets in each species library was uniform, and the performance of targets among independent exon captures was highly reproducible. There was no decrease in coverage among chipmunk species, which showed up to 1.5% sequence divergence in coding regions. We did observe a decline in capture performance of a subset of targets designed from a much more divergent ground squirrel genome (30 My), however, over 90% of the targets were also recovered. Final assemblies yielded over ten thousand orthologous loci (similar to 3.6 Mb) with thousands of fixed and polymorphic SNPs among species identified. Conclusions: Our study demonstrates the potential of a transcriptome-enabled, multiplexed, exon capture method to create thousands of informative markers for population genomic and phylogenetic studies in non-model species across the tree of life

Welcome, How Can I Help You? Design Considerations for a Virtual Reality Environment to Support the Orientation of Online Initial Teacher Education Students

Alongside the rapid and broad uptake of online learning in higher education, fully online students report feeling isolated and disconnected from their institutions. Although formal course content may be expertly designed to engage online learners, much of the information provided to support higher education students’ orientation to the institution and to study is presented online in a written static form. Such presentations may not be accessible and engaging and may contribute to feelings of disconnection. Technologies such as virtual reality (VR) are being used in higher education to engage, motivate and connect students in their learning. This paper reports on the early design stages for a VR that aims to support initial teacher education students to connect and engage with key orienting information. The design of the VR was achieved by following a user-centred, iterative engineering design process and design principles of spatiality, interaction and narrative. The VR environment emulates the School of Education’s physical, on-campus reception area to provide an immersive experience where students have a choice in the types and format of key study information they receive. This experience was designed to be utilised in online orientation but also throughout students’ first year of study. Future research directions include collecting student responses to the VR to inform how students can be involved in enhancing the VR so that it supports their learning and sense of connection. Furthermore, future research can aim for the expansion of the VR inclusive of additional information, rooms and buildings and increased capabilities such as gamification and mobile access. This will enable the creation of a valuable teaching resource for online programs

Temporal genomic contrasts reveal rapid evolutionary responses in an alpine mammal during recent climate change

Many species have experienced dramatic changes in their abundance and distribution during recent climate change, but it is often unclear whether such ecological responses are accompanied by evolutionary change. We used targeted exon sequencing of 294 museum specimens (160 historic, 134 modern) to generate independent temporal genomic contrasts spanning a century of climate change (1911–2012) for two co-distributed chipmunk species: an endemic alpine specialist (Tamias alpinus) undergoing severe range contraction and a stable mid-elevation species (T. speciosus). Using a novel analytical approach, we reconstructed the demographic histories of these populations and tested for evidence of recent positive directional selection. Only the retracting species showed substantial population genetic fragmentation through time and this was coupled with positive selection and substantial shifts in allele frequencies at a gene, Alox15, involved in regulation of inflammation and response to hypoxia. However, these rapid population and gene-level responses were not detected in an analogous temporal contrast from another area where T. alpinus has also undergone severe range contraction. Collectively, these results highlight that evolutionary responses may be variable and context dependent across populations, even when they show seemingly synchronous ecological shifts. Our results demonstrate that temporal genomic contrasts can be used to detect very recent evolutionary responses within and among contemporary populations, even in the face of complex demographic changes. Given the wealth of specimens archived in natural history museums, comparative analyses of temporal population genomic data have the potential to improve our understanding of recent and ongoing evolutionary responses to rapidly changing environments

Observations of SN 2017ein Reveal Shock Breakout Emission and A Massive Progenitor Star for a Type Ic Supernova

We present optical and ultraviolet observations of nearby type Ic supernova SN 2017ein as well as detailed analysis of its progenitor properties from both the early-time observations and the prediscovery Hubble Space Telescope (HST) images. The optical light curves started from within one day to $\sim$275 days after explosion, and optical spectra range from $\sim$2 days to $\sim$90 days after explosion. Compared to other normal SNe Ic like SN 2007gr and SN 2013ge, \mbox{SN 2017ein} seems to have more prominent C{\footnotesize II} absorption and higher expansion velocities in early phases, suggestive of relatively lower ejecta mass. The earliest photometry obtained for \mbox{SN 2017ein} show indications of shock cooling. The best-fit obtained by including a shock cooling component gives an estimate of the envelope mass as $\sim$0.02 M$_{\odot}$ and stellar radius as 8$\pm$4 R$_{\odot}$. Examining the pre-explosion images taken with the HST WFPC2, we find that the SN position coincides with a luminous and blue point-like source, with an extinction-corrected absolute magnitude of M$_V$$\sim$$-$8.2 mag and M$_I$$\sim$$-$7.7 mag.Comparisons of the observations to the theoretical models indicate that the counterpart source was either a single WR star or a binary with whose members had high initial masses, or a young compact star cluster. To further distinguish between different scenarios requires revisiting the site of the progenitor with HST after the SN fades away.Comment: 28 pages, 19 figures; accepted for publication in The Astrophysical Journa

Distinguishing Dark Matter Annihilation Enhancement Scenarios via Halo Shapes

Sommerfeld enhancement and Breit-Wigner enhancement of the dark matter annihilation have been proposed to explain the "boost factor" which is suggested by observed cosmic ray excesses. Although these two scenarios can provide almost indistinguishable effects on the cosmic ray fluxes, the cross sections of the self-interaction in those enhancement mechanisms are drastically different. As a result, we show that they can be distinguished by examining the effects of the self-interaction on the halo shapes. In Sommerfeld enhancement models with m_phi<100MeV and m_DM<3TeV, the self-interaction can leave observable imprints in the galactic dynamics, while dark matter is effectively collisionless in Breit-Wigner models.Comment: 4 pages, 1 figur

Transcriptional profiles of bovine in vivo pre-implantation development

© 2014 Jiang et al.; licensee BioMed Central Ltd. Background: During mammalian pre-implantation embryonic development dramatic and orchestrated changes occur in gene transcription. The identification of the complete changes has not been possible until the development of the Next Generation Sequencing Technology.Results: Here we report comprehensive transcriptome dynamics of single matured bovine oocytes and pre-implantation embryos developed in vivo. Surprisingly, more than half of the estimated 22,000 bovine genes, 11,488 to 12,729 involved in more than 100 pathways, is expressed in oocytes and early embryos. Despite the similarity in the total numbers of genes expressed across stages, the nature of the expressed genes is dramatically different. A total of 2,845 genes were differentially expressed among different stages, of which the largest change was observed between the 4- and 8-cell stages, demonstrating that the bovine embryonic genome is activated at this transition. Additionally, 774 genes were identified as only expressed/highly enriched in particular stages of development, suggesting their stage-specific roles in embryogenesis. Using weighted gene co-expression network analysis, we found 12 stage-specific modules of co-expressed genes that can be used to represent the corresponding stage of development. Furthermore, we identified conserved key members (or hub genes) of the bovine expressed gene networks. Their vast association with other embryonic genes suggests that they may have important regulatory roles in embryo development; yet, the majority of the hub genes are relatively unknown/under-studied in embryos. We also conducted the first comparison of embryonic expression profiles across three mammalian species, human, mouse and bovine, for which RNA-seq data are available. We found that the three species share more maternally deposited genes than embryonic genome activated genes. More importantly, there are more similarities in embryonic transcriptomes between bovine and humans than between humans and mice, demonstrating that bovine embryos are better models for human embryonic development.Conclusions: This study provides a comprehensive examination of gene activities in bovine embryos and identified little-known potential master regulators of pre-implantation development

A Water Resource Management Model, Upper Jordan River Drainage, Utah

As demands upon available water supplies increase within a river basin, there is an accompanying increase in the need to assess the downstream consequences resulting from changes at specific locations within the hydrologic system. This problem is approached in this study by digital computer simulation of the hydrologic system. Modeling concepts are based upon basic relationships which describe the various hydrologic processes. Within a hydrologic system these relationships are linked by the continuity-of-mass principle which requires a mass balance at all points. Spatial resolution is achieved by considering the modeled area as a series of subbasins. The time increment adopted for the model is one month, so that time varying quantities are expressed in terms of mean monthly values. The model is general in nature and is applied to a particular hydrologic system through a programmed verification procedure whereby model coefficients are evaluated for the particular system. In this study the model was applied to the Provo River basin of northern Utah, with emphases being placed upon water rights and operation of storage reservoirs within the system, including Utah Lake. The simulation model consists of three specific parts, namely: (1) parameter optimization; (2) river basin management; and (3) Utah Lake operation. The parameter optimization submodel identifies the model parameters for each subbasin through application of a parameter optimization technique. The river basin management submodel, using the optimized parameters, simulated the hydrologic response of the system to various water resources management alternatives. The Utah Lake operation submodel is linked with the river basin management submodel to comprise a combined Utah Lake operations model. Some comparisons between observed and computed outflow hydrographs at various points within the Provo River basin are shown. The utility of the model for predicting the effects of various possible water resource management alternatives is demonstrated