Analyzing Symmetry of Stream Valleys to Characterize Possible Neogene Uplift in the Blue Ridge Mountains of North Carolina

Recent work has suggested that parts of the Appalachian Mountains were uplifted during the Neogene, based on stream knickpoint analysis (Gallen et al., 2013; Miller et al., 2013). Analysis of the symmetry of valleys has the potential to indicate tectonic activity by determining migration trends of channels. Tectonic quiescence promotes lateral migration of stream bends. This creates asymmetrical bend valleys with shallow point bars and steep cut banks. Uplift promotes downcutting over lateral migration, producing symmetrical stream valleys. Using LIDAR data and ArcMap software, I quantified the symmetry of stream valleys in the Blue Ridge Mountains of western North Carolina. I calculated the symmetry of valleys by dividing the right valley slope by the left valley slope to form ratios ranging from 0 to 1, with 1 indicative of a symmetrical valley. Where the right slope exceeded the left slope, I inverted the ratio to avoid numbers greater than 1. I measured slope ratios across the Broad, Cullasaja, French Broad, Linville, New, Pigeon, Toe, and Tuckasegee Rivers. To separate similar symmetry values between areas of gentle and steep topography, I multiplied the symmetry value by the average of the right and left slopes. The resultant values were then combined with a knickpoint propagation model to project areas of equilibrating streams and relict topography. Active landscapes were projected across most of the Blue Ridge Mountains in North Carolina, excluding the French Broad river valley, which was either unaffected by Neogene activity or equilibrated in the distant past. These conclusions agree with hypothesized locations of active landscapes, in addition to projecting new potential locations of rejuvenation.Bachelor of Scienc

Linking Proteomic and Transcriptional Data through the Interactome and Epigenome Reveals a Map of Oncogene-induced Signaling

Cellular signal transduction generally involves cascades of post-translational protein modifications that rapidly catalyze changes in protein-DNA interactions and gene expression. High-throughput measurements are improving our ability to study each of these stages individually, but do not capture the connections between them. Here we present an approach for building a network of physical links among these data that can be used to prioritize targets for pharmacological intervention. Our method recovers the critical missing links between proteomic and transcriptional data by relating changes in chromatin accessibility to changes in expression and then uses these links to connect proteomic and transcriptome data. We applied our approach to integrate epigenomic, phosphoproteomic and transcriptome changes induced by the variant III mutation of the epidermal growth factor receptor (EGFRvIII) in a cell line model of glioblastoma multiforme (GBM). To test the relevance of the network, we used small molecules to target highly connected nodes implicated by the network model that were not detected by the experimental data in isolation and we found that a large fraction of these agents alter cell viability. Among these are two compounds, ICG-001, targeting CREB binding protein (CREBBP), and PKF118–310, targeting β-catenin (CTNNB1), which have not been tested previously for effectiveness against GBM. At the level of transcriptional regulation, we used chromatin immunoprecipitation sequencing (ChIP-Seq) to experimentally determine the genome-wide binding locations of p300, a transcriptional co-regulator highly connected in the network. Analysis of p300 target genes suggested its role in tumorigenesis. We propose that this general method, in which experimental measurements are used as constraints for building regulatory networks from the interactome while taking into account noise and missing data, should be applicable to a wide range of high-throughput datasets.National Science Foundation (U.S.) (DB1-0821391)National Institutes of Health (U.S.) (Grant U54-CA112967)National Institutes of Health (U.S.) (Grant R01-GM089903)National Institutes of Health (U.S.) (P30-ES002109

Designing Hybrid Gifts

Hybrid gifting combines physical artefacts and experiences with digital interactivity to generate new kinds of gifts. Our review details how gifting is a complex social phenomenon and how digital gifting is less engaging than physical gifting for both givers and receivers. Employing a Research Through Design approach, we developed a portfolio of four hybrid gifting experiences: an augmented advent calendar; edible music tracks; personalised museum tours; and a narrated city walk. Our reflection addresses three concepts: hybrid wrapping where physical gifts become wrapped in digital media and vice versa; the importance of effortful interactions that are visible and pleasurable; and the need to consider social obligation, including opportunities for acknowledgement and reciprocation, dealing with embarrassment, and recognising the distinction between giving and sharing. Our concepts provide guidance to practitioners who wish to design future gifting experiences while helping HCI researchers engage with the concept of gifting in a nuanced way

Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.

We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development

Universal DNA methylation age across mammalian tissues

DATA AVAILABILITY STATEMENT : The individual-level data from the Mammalian Methylation Consortium can be accessed from several online locations. All data from the Mammalian Methylation Consortium are posted on Gene Expression Omnibus (complete dataset, GSE223748). Subsets of the datasets can also be downloaded from accession numbers GSE174758, GSE184211, GSE184213, GSE184215, GSE184216, GSE184218, GSE184220, GSE184221, GSE184224, GSE190660, GSE190661, GSE190662, GSE190663, GSE190664, GSE174544, GSE190665, GSE174767, GSE184222, GSE184223, GSE174777, GSE174778, GSE173330, GSE164127, GSE147002, GSE147003, GSE147004, GSE223943 and GSE223944. Additional details can be found in Supplementary Note 2. The mammalian data can also be downloaded from the Clock Foundation webpage: https://clockfoundation.org/MammalianMethylationConsortium. The mammalian methylation array is available through the non-profit Epigenetic Clock Development Foundation (https://clockfoundation.org/). The manifest file of the mammalian array and genome annotations of CpG sites can be found on Zenodo (10.5281/zenodo.7574747). All other data supporting the findings of this study are available from the corresponding author upon reasonable request. The chip manifest files, genome annotations of CpG sites and the software code for universal pan-mammalian clocks can be found on GitHub95 at https://github.com/shorvath/MammalianMethylationConsortium/tree/v2.0.0. The individual R code for the universal pan-mammalian clocks, EWAS analysis and functional enrichment studies can be also found in the Supplementary Code.SUPPLEMENTARY MATERIAL 1 : Supplementary Tables 1–3 and Notes 1–6.SUPPLEMENTARY MATERIAL 2 : Reporting SummarySUPPLEMENTARY MATERIAL 3 : Supplementary Data 1–14.SUPPLEMENTARY MATERIAL 4 : Supplementary Code.Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.https://www.nature.com/nataginghj2024Zoology and EntomologySDG-15:Life on lan

Dating the Cenozoic Incision History of the Tennessee and Shenandoah Rivers with Cosmogenic Nuclides and 40AR/39AR in Manganese Oxides

The post-orogenic history of the Appalachian Mountains, particularly the persistence of rough topography and the degree of river incision throughout the region, has been a longstanding focus of geomorphology studies. Numerous models have been developed to explain the evolution of this landscape, variously invoking episodic or continuous processes of uplift and erosion to drive the generation or reduction of topographic relief. Recently, late Cenozoic uplift has found favor as a mechanism for rejuvenating the topography of the southern and central Appalachians. This hypothesis has drawn on longitudinal river profiles, seismic tomography, and offshore sediment records as evidence of Neogene uplift. Radiometric dating of surficial deposits provides a means to directly test models of episodic and continuous landscape evolution, as well as the Neogene uplift hypothesis. The research described in this thesis dates surficial sediments (river terraces, alluvial fans, and a filled sinkhole) and supergene manganese oxides using 26Al/10Be burial dating and 40Ar/39Ar geochronology, respectively. Our cosmogenic 26Al/10Be dating provides detailed histories of aggradation and incision along the Shenandoah and Tennessee Rivers since the early Pliocene. 40Ar/39Ar dating of manganese oxides permits estimates of surface preservation and denudation in the Shenandoah Valley and nearby watersheds throughout the Cenozoic. The results of our work in the Shenandoah Valley, Tennessee River basin, and intervening areas indicate that the Appalachians experienced no significant pulse of uplift during the Cenozoic. Long-term preservation of supergene manganese oxides dates as far back as the Eocene, demonstrating minimal denudation and discontinuous formation that lend evidence to episodic landscape evolution models. Cosmogenic 26Al/10Be burial ages along the Shenandoah and Tennessee Rivers reveal Pliocene aggradation, with enhanced deposition in the Shenandoah Valley during the mid-Piacenzian Warm Period. Both rivers likely experienced incision during the Pleistocene, likely due to climatic fluctuations. These results demonstrate that while the Appalachian landscape has remained largely unchanged for tens of millions of years, rapid Pleistocene changes in base level recently triggered significant incision of major drainages