Reward-Based Crowdfunding Research and Practice

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Validation of Skeletal Muscle cis-Regulatory Module Predictions Reveals Nucleotide Composition Bias in Functional Enhancers

We performed a genome-wide scan for muscle-specific cis-regulatory modules (CRMs) using three computational prediction programs. Based on the predictions, 339 candidate CRMs were tested in cell culture with NIH3T3 fibroblasts and C2C12 myoblasts for capacity to direct selective reporter gene expression to differentiated C2C12 myotubes. A subset of 19 CRMs validated as functional in the assay. The rate of predictive success reveals striking limitations of computational regulatory sequence analysis methods for CRM discovery. Motif-based methods performed no better than predictions based only on sequence conservation. Analysis of the properties of the functional sequences relative to inactive sequences identifies nucleotide sequence composition can be an important characteristic to incorporate in future methods for improved predictive specificity. Muscle-related TFBSs predicted within the functional sequences display greater sequence conservation than non-TFBS flanking regions. Comparison with recent MyoD and histone modification ChIP-Seq data supports the validity of the functional regions

Stable Isotope Biogeochemistry of Seabird Guano Fertilization: Results from Growth Chamber Studies with Maize (Zea Mays)

Stable isotope analysis is being utilized with increasing regularity to examine a wide range of issues (diet, habitat use, migration) in ecology, geology, archaeology, and related disciplines. A crucial component to these studies is a thorough understanding of the range and causes of baseline isotopic variation, which is relatively poorly understood for nitrogen (δ(15)N). Animal excrement is known to impact plant δ(15)N values, but the effects of seabird guano have not been systematically studied from an agricultural or horticultural standpoint.This paper presents isotopic (δ(13)C and δ(15)N) and vital data for maize (Zea mays) fertilized with Peruvian seabird guano under controlled conditions. The level of (15)N enrichment in fertilized plants is very large, with δ(15)N values ranging between 25.5 and 44.7‰ depending on the tissue and amount of fertilizer applied; comparatively, control plant δ(15)N values ranged between -0.3 and 5.7‰. Intraplant and temporal variability in δ(15)N values were large, particularly for the guano-fertilized plants, which can be attributed to changes in the availability of guano-derived N over time, and the reliance of stored vs. absorbed N. Plant δ(13)C values were not significantly impacted by guano fertilization. High concentrations of seabird guano inhibited maize germination and maize growth. Moreover, high levels of seabird guano greatly impacted the N metabolism of the plants, resulting in significantly higher tissue N content, particularly in the stalk.The results presented in this study demonstrate the very large impact of seabird guano on maize δ(15)N values. The use of seabird guano as a fertilizer can thus be traced using stable isotope analysis in food chemistry applications (certification of organic inputs). Furthermore, the fertilization of maize with seabird guano creates an isotopic signature very similar to a high-trophic level marine resource, which must be considered when interpreting isotopic data from archaeological material

Mapping genetic variations to three- dimensional protein structures to enhance variant interpretation: a proposed framework

The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to discuss unmet needs. The overarching goal of the workshop was to address the question: what can be done together as a community to advance the integration of genetic variants and 3D protein structures that could not be done by a single investigator or laboratory? Here we describe the workshop outcomes, review the state of the field, and propose the development of a framework with which to promote progress in this arena. The framework will include a set of standard formats, common ontologies, a common application programming interface to enable interoperation of the resources, and a Tool Registry to make it easy to find and apply the tools to specific analysis problems. Interoperability will enable integration of diverse data sources and tools and collaborative development of variant effect prediction methods

Refinement of Miocene sea level and monsoon events from the sedimentary archive of the Maldives (Indian Ocean)

International Ocean Discovery Program (IODP) Expedition 359 cored sediments from eight borehole locations in the carbonate platform of the Maldives in the Indian Ocean. The expedition set out to unravel the timing of Neogene climate changes, in particular the evolution of the South Asian monsoon and fluctuations of the sea level. The timing of these changes are assessed by dating resultant sedimentary alterations that mark stratigraphic turning points in the Neogene Maldives platform system. The first four turning points during the early and middle Miocene are related to sea-level changes. These are reliably recorded in the stratigraphy of the carbonate sequences in which sequence boundaries provide the ages of the sea-level lowstand. Phases of aggradational platform growth give precise age brackets of long-term sea-level high stands during the early Miocene and the early to middle Miocene Climate Optimum that is dated here between 17 to 15.1 Ma. The subsequent middle Miocene cooling coincident with the eastern Antarctic ice sheet expansion resulted in a long-term lowering of sea level that is reflected by a progradational platform growth. The change in platform architecture from aggradation to progradation marks this turning point at 15.1 Ma. An abrupt change in sedimentation pattern is recognized across the entire archipelago at a sequence boundary dated as 12.9–13 Ma. At this turning point, the platform sedimentation switched to a current-controlled mode when the monsoon-wind-driven circulation started in the Indian Ocean. The similar age of the onset of drift deposition from monsoon-wind-driven circulation across the entire archipelago indicates an abrupt onset of monsoon winds in the Indian Ocean. Ten unconformities dissect the drift sequences, attesting changes in current strength or direction that are likely caused by the combined product of changes in the monsoon-wind intensity and sea level fluctuations in the last 13 Ma. A major shift in the drift packages is dated with 3.8 Ma that coincides with the end of stepwise platform drowning and a reduction of the oxygen minimum zone in the Inner Sea. The strata of the Maldives platform provides a detailed record of the extrinsic controlling factors on carbonate platform growth through time. This potential of carbonate platforms for dating the Neogene climate and current changes has been exploited in other platforms drilled by the Ocean Drilling Program. For example, Great Bahama Bank, the Queensland Plateau, and the platforms on the Marion Plateau show similar histories with sediment architectures driven by sea level in their early history (early to middle Miocene) replaced by current-driven drowning or partial drowning during their later history (Late Miocene). In all three platform systems, the influence of currents on sedimentations is reported between 11 and 13 Ma

A genome-wide genetic map of NB-LRR disease resistance loci in potato

Like all plants, potato has evolved a surveillance system consisting of a large array of genes encoding for immune receptors that confer resistance to pathogens and pests. The majority of these so-called resistance or R proteins belong to the super-family that harbour a nucleotide binding and a leucine-rich-repeat domain (NB-LRR). Here, sequence information of the conserved NB domain was used to investigate the genome-wide genetic distribution of the NB-LRR resistance gene loci in potato. We analysed the sequences of 288 unique BAC clones selected using filter hybridisation screening of a BAC library of the diploid potato clone RH89-039-16 (S. tuberosum ssp. tuberosum) and a physical map of this BAC library. This resulted in the identification of 738 partial and full-length NB-LRR sequences. Based on homology of these sequences with known resistance genes, 280 and 448 sequences were classified as TIR-NB-LRR (TNL) and CC-NB-LRR (CNL) sequences, respectively. Genetic mapping revealed the presence of 15 TNL and 32 CNL loci. Thirty-six are novel, while three TNL loci and eight CNL loci are syntenic with previously identified functional resistance genes. The genetic map was complemented with 68 universal CAPS markers and 82 disease resistance trait loci described in literature, providing an excellent template for genetic studies and applied research in potato