Preparation and Rationale for a Patient-Centered Clinical Outcome Assessment Set of Fluid Overload for Drug Development in Nephrotic Syndrome.

Introduction: Fluid overload is a source of substantial morbidity for adults and children with nephrotic syndrome (NS). Preparation and Rationale for a Fluid Overload in Nephrotic Syndrome Clinical Outcomes Assessment Set for Drug Development (Prepare-NS, 5UG3FD007308) was funded by the US Food and Drug Administration to develop a core set of patient-reported and observer-reported (for young children) outcome measures of fluid overload for use in pharmaceutical trials across the lifespan.

Methods: The Prepare-NS study team developed the proposed context of use with input from stakeholders.

A contiguous de novo genome assembly of sugar beet EL10 (Beta vulgaris L.).

A contiguous assembly of the inbred 'EL10' sugar beet (Beta vulgaris ssp. vulgaris) genome was constructed using PacBio long-read sequencing, BioNano optical mapping, Hi-C scaffolding, and Illumina short-read error correction. The EL10.

Integration of multi-omics data reveals cis-regulatory variants that are associated with phenotypic differentiation of eastern from western pigs.

Background: The genetic mechanisms that underlie phenotypic differentiation in breeding animals have important implications in evolutionary biology and agriculture. However, the contribution of cis-regulatory variants to pig phenotypes is poorly understood. Therefore, our aim was to elucidate the molecular mechanisms by which non-coding variants cause phenotypic differences in pigs by combining evolutionary biology analyses and functional genomics.

Gaur genome reveals expansion of sperm odorant receptors in domesticated cattle.

Background: The gaur (Bos gaurus) is the largest extant wild bovine species, native to South and Southeast Asia, with unique traits, and is listed as vulnerable by the International Union for Conservation of Nature (IUCN).

Results: We report the first gaur reference genome and identify three biological pathways including lysozyme activity, proton transmembrane transporter activity, and oxygen transport with significant changes in gene copy number in gaur compared to other mammals. These may reflect adaptation to challenges related to climate and nutrition.

Generating lineage-resolved, complete metagenome-assembled genomes from complex microbial communities.

Microbial communities might include distinct lineages of closely related organisms that complicate metagenomic assembly and prevent the generation of complete metagenome-assembled genomes (MAGs). Here we show that deep sequencing using long (HiFi) reads combined with Hi-C binning can address this challenge even for complex microbial communities. Using existing methods, we sequenced the sheep fecal metagenome and identified 428 MAGs with more than 90% completeness, including 44 MAGs in single circular contigs.

The genome of the zebra mussel, Dreissena polymorpha: a resource for comparative genomics, invasion genetics, and biocontrol.

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves. Although the D.

Genomic Resources to Guide Improvement of the Shea Tree.

A defining component of agroforestry parklands across Sahelo-Sudanian Africa (SSA), the shea tree () is central to sustaining local livelihoods and the farming environments of rural communities. Despite its economic and cultural value, however, not to mention the ecological roles it plays as a dominant parkland species, shea remains semi-domesticated with virtually no history of systematic genetic improvement. In truth, shea's extended juvenile period makes traditional breeding approaches untenable; but the opportunity for genome-assisted breeding is immense, provided the foundational resources are available.

Extended haplotype-phasing of long-read de novo genome assemblies using Hi-C.

Haplotype-resolved genome assemblies are important for understanding how combinations of variants impact phenotypes. To date, these assemblies have been best created with complex protocols, such as cultured cells that contain a single-haplotype (haploid) genome, single cells where haplotypes are separated, or co-sequencing of parental genomes in a trio-based approach. These approaches are impractical in most situations.

Genome sequence of Monilinia vaccinii-corymbosi sheds light on mummy berry disease infection of blueberry and mating type.

Mummy berry disease, caused by the fungal pathogen Monilinia vaccinii-corymbosi (Mvc), is one of the most economically important diseases of blueberries in North America. Mvc is capable of inducing two separate blighting stages during its life cycle. Infected fruits are rendered mummified and unmarketable.

Identifying the causes and consequences of assembly gaps using a multiplatform genome assembly of a bird-of-paradise.

Genome assemblies are currently being produced at an impressive rate by consortia and individual laboratories. The low costs and increasing efficiency of sequencing technologies now enable assembling genomes at unprecedented quality and contiguity. However, the difficulty in assembling repeat-rich and GC-rich regions (genomic "dark matter") limits insights into the evolution of genome structure and regulatory networks.

Degradation of Recalcitrant Polyurethane and Xenobiotic Additives by a Selected Landfill Microbial Community and Its Biodegradative Potential Revealed by Proximity Ligation-Based Metagenomic Analysis.

Polyurethanes (PU) are the sixth most produced plastics with around 18-million tons in 2016, but since they are not recyclable, they are burned or landfilled, generating damage to human health and ecosystems. To elucidate the mechanisms that landfill microbial communities perform to attack recalcitrant PU plastics, we studied the degradative activity of a mixed microbial culture, selected from a municipal landfill by its capability to grow in a water PU dispersion (WPUD) as the only carbon source, as a model for the BP8 landfill microbial community. The WPUD contains a polyether-polyurethane-acrylate (PE-PU-A) copolymer and xenobiotic additives (-methylpyrrolidone, isopropanol and glycol ethers).

Mapping and Dynamics of Regulatory DNA in Maturing Siliques.

The genome is reprogrammed during development to produce diverse cell types, largely through altered expression and activity of key transcription factors. The accessibility and critical functions of epidermal cells have made them a model for connecting transcriptional events to development in a range of model systems. In and many other plants, fertilization triggers differentiation of specialized epidermal seed coat cells that have a unique morphology caused by large extracellular deposits of polysaccharides.

Divergent evolutionary trajectories following speciation in two ectoparasitic honey bee mites.

Multispecies host-parasite evolution is common, but how parasites evolve after speciating remains poorly understood. Shared evolutionary history and physiology may propel species along similar evolutionary trajectories whereas pursuing different strategies can reduce competition. We test these scenarios in the economically important association between honey bees and ectoparasitic mites by sequencing the genomes of the sister mite species and .

Assignment of virus and antimicrobial resistance genes to microbial hosts in a complex microbial community by combined long-read assembly and proximity ligation.

We describe a method that adds long-read sequencing to a mix of technologies used to assemble a highly complex cattle rumen microbial community, and provide a comparison to short read-based methods. Long-read alignments and Hi-C linkage between contigs support the identification of 188 novel virus-host associations and the determination of phage life cycle states in the rumen microbial community. The long-read assembly also identifies 94 antimicrobial resistance genes, compared to only seven alleles in the short-read assembly.

Linking the resistome and plasmidome to the microbiome.

The rapid spread of antibiotic resistance among bacterial pathogens is a serious human health threat. While a range of environments have been identified as reservoirs of antibiotic resistance genes (ARGs), we lack understanding of the origins of these ARGs and their spread from environment to clinic. This is partly due to our inability to identify the natural bacterial hosts of ARGs and the mobile genetic elements that mediate this spread, such as plasmids and integrons.

Integrated Functional Genomic Analysis Enables Annotation of Kidney Genome-Wide Association Study Loci.

Background: Linking genetic risk loci identified by genome-wide association studies (GWAS) to their causal genes remains a major challenge. Disease-associated genetic variants are concentrated in regions containing regulatory DNA elements, such as promoters and enhancers. Although researchers have previously published DNA maps of these regulatory regions for kidney tubule cells and glomerular endothelial cells, maps for podocytes and mesangial cells have not been available.

Chromosome rearrangements shape the diversification of secondary metabolism in the cyclosporin producing fungus Tolypocladium inflatum.

Background: Genes involved in production of secondary metabolites (SMs) in fungi are exceptionally diverse. Even strains of the same species may exhibit differences in metabolite production, a finding that has important implications for drug discovery. Unlike in other eukaryotes, genes producing SMs are often clustered and co-expressed in fungal genomes, but the genetic mechanisms involved in the creation and maintenance of these secondary metabolite biosynthetic gene clusters (SMBGCs) remains poorly understood.

Chromosome-scale scaffolding of the black raspberry ( L.) genome based on chromatin interaction data.

Black raspberry ( L.) is a niche fruit crop valued for its flavor and potential health benefits. The improvement of fruit and cane characteristics via molecular breeding technologies has been hindered by the lack of a high-quality reference genome.

Improvement of the Threespine Stickleback Genome Using a Hi-C-Based Proximity-Guided Assembly.

Scaffolding genomes into complete chromosome assemblies remains challenging even with the rapidly increasing sequence coverage generated by current next-generation sequence technologies. Even with scaffolding information, many genome assemblies remain incomplete. The genome of the threespine stickleback (Gasterosteus aculeatus), a fish model system in evolutionary genetics and genomics, is not completely assembled despite scaffolding with high-density linkage maps.

Single-molecule sequencing and chromatin conformation capture enable de novo reference assembly of the domestic goat genome.

The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus) based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping.

Mapping and dynamics of regulatory DNA and transcription factor networks in A. thaliana.

Our understanding of gene regulation in plants is constrained by our limited knowledge of plant cis-regulatory DNA and its dynamics. We mapped DNase I hypersensitive sites (DHSs) in A. thaliana seedlings and used genomic footprinting to delineate ∼ 700,000 sites of in vivo transcription factor (TF) occupancy at nucleotide resolution.

Low-cost and disposable pressure sensor mat for non-invasive sleep and movement monitoring applications.

Sleep has profound effects on the physical and mental well-being of an individual. The National Institutes of Health (NIH) Sleep Disorder Research Plan gives particular emphasis to non-invasive sleep monitoring methods. Older adults experience sleep fragmentation due to sleep disorders.

From transcriptome analysis to therapeutic anti-CD40L treatment in the SOD1 model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive loss of motor neurons. Using unbiased transcript profiling in an ALS mouse model, we identified a role for the co-stimulatory pathway, a key regulator of immune responses. Furthermore, we observed that this pathway is upregulated in the blood of 56% of human patients with ALS.

Controlled polymerization of substituted diacetylene self-organized monolayers confined in molecule corrals.

We have shown that STM-tip-induced chain polymerization of 10,12-tricosadiynoic acid (TCDA) in a self-organized monolayer at the liquid-solid interface of TCDA on highly oriented pyrolytic graphite is possible. The oligomers thus produced started at the point where a voltage pulse was applied between the STM tip and the sample during a short period when the feedback condition was momentarily suspended (as it is for scanning tunneling spectroscopy). Polymerization probabilities depended upon the length of the applied voltage pulse and were generally higher for longer pulse widths in the 10-ms to 100-micros time scales, approaching unit probability for the former and decreasing quickly to a few tens of percent for the latter.