Publications by authors named "Shawn Sullivan"

18 Publications

  • Page 1 of 1

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

G3 (Bethesda) 2021 Feb;11(2)

Department of Horticultural Science, North Carolina State University, Raleigh, NC 27695, USA.

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. Genomic data for this pathogen is lacking, but could be useful in understanding the reproductive biology of Mvc and the mechanisms it deploys to facilitate host infection. In this study, PacBio sequencing and Hi-C interaction data were utilized to create a chromosome-scale reference genome for Mvc. The genome comprises nine chromosomes with a total length of 30 Mb, an N50 length of 4.06 Mb, and an average 413X sequence coverage. A total of 9399 gene models were predicted and annotated, and BUSCO analysis revealed that 98% of 1,438 searched conserved eukaryotic genes were present in the predicted gene set. Potential effectors were identified, and the mating-type (MAT) locus was characterized. Biotrophic effectors allow the pathogen to avoid recognition by the host plant and evade or mitigate host defense responses during the early stages of fruit infection. Following locule colonization, necrotizing effectors promote the mummification of host tissues. Potential biotrophic effectors utilized by Mvc include chorismate mutase for reducing host salicylate and necrotrophic effectors include necrosis-inducing proteins and hydrolytic enzymes for macerating host tissue. The MAT locus sequences indicate the potential for homothallism in the reference genome, but a deletion allele of the MAT locus, characterized in a second isolate, indicates heterothallism. Further research is needed to verify the roles of individual effectors in virulence and to determine the role of the MAT locus in outcrossing and population genotypic diversity.
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http://dx.doi.org/10.1093/g3journal/jkaa052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022979PMC
February 2021

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

Mol Ecol Resour 2021 Jan 10;21(1):263-286. Epub 2020 Oct 10.

Department of Ecology and Genetics-Evolutionary Biology, Science for Life Laboratories, Uppsala University, Uppsala, Sweden.

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. Here, we compare the efficiency of currently available sequencing technologies (short/linked/long reads and proximity ligation maps) and combinations thereof in assembling genomic dark matter. By adopting different de novo assembly strategies, we compare individual draft assemblies to a curated multiplatform reference assembly and identify the genomic features that cause gaps within each assembly. We show that a multiplatform assembly implementing long-read, linked-read and proximity sequencing technologies performs best at recovering transposable elements, multicopy MHC genes, GC-rich microchromosomes and the repeat-rich W chromosome. Telomere-to-telomere assemblies are not a reality yet for most organisms, but by leveraging technology choice it is now possible to minimize genome assembly gaps for downstream analysis. We provide a roadmap to tailor sequencing projects for optimized completeness of both the coding and noncoding parts of nonmodel genomes.
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http://dx.doi.org/10.1111/1755-0998.13252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757076PMC
January 2021

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

Front Microbiol 2019 22;10:2986. Epub 2020 Jan 22.

Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico.

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). To identify the changes that the BP8 microbial community culture generates to the WPUD additives and copolymer, we performed chemical and physical analyses of the biodegradation process during 25 days of cultivation. These analyses included Nuclear magnetic resonance, Fourier transform infrared spectroscopy, Thermogravimetry, Differential scanning calorimetry, Gel permeation chromatography, and Gas chromatography coupled to mass spectrometry techniques. Moreover, for revealing the BP8 community structure and its genetically encoded potential biodegradative capability we also performed a proximity ligation-based metagenomic analysis. The additives present in the WPUD were consumed early whereas the copolymer was cleaved throughout the 25-days of incubation. The analysis of the biodegradation process and the identified biodegradation products showed that BP8 cleaves esters, C-C, and the recalcitrant aromatic urethanes and ether groups by hydrolytic and oxidative mechanisms, both in the soft and the hard segments of the copolymer. The proximity ligation-based metagenomic analysis allowed the reconstruction of five genomes, three of them from novel species. In the metagenome, genes encoding known enzymes, and putative enzymes and metabolic pathways accounting for the biodegradative activity of the BP8 community over the additives and PE-PU-A copolymer were identified. This is the first study revealing the genetically encoded potential biodegradative capability of a microbial community selected from a landfill, that thrives within a WPUD system and shows potential for bioremediation of polyurethane- and xenobiotic additives-contamitated sites.
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http://dx.doi.org/10.3389/fmicb.2019.02986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987047PMC
January 2020

Mapping and Dynamics of Regulatory DNA in Maturing Siliques.

Front Plant Sci 2019 14;10:1434. Epub 2019 Nov 14.

Department of Genome Sciences, University of Washington, Seattle, WA, United States.

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. Here, we used DNase I-seq to generate regulatory landscapes of seeds at two critical time points in seed coat maturation (4 and 7 DPA), enriching for seed coat cells with the INTACT method. We found over 3,000 developmentally dynamic regulatory DNA elements and explored their relationship with nearby gene expression. The dynamic regulatory elements were enriched for motifs for several transcription factors families; most notably the TCP family at the earlier time point and the MYB family at the later one. To assess the extent to which the observed regulatory sites in seeds added to previously known regulatory sites in we compared our data to 11 other data sets generated with 7-day-old seedlings for diverse tissues and conditions. Surprisingly, over a quarter of the regulatory, i.e. accessible, bases observed in seeds were novel. Notably, plant regulatory landscapes from different tissues, cell types, or developmental stages were more dynamic than those generated from bulk tissue in response to environmental perturbations, highlighting the importance of extending studies of regulatory DNA to single tissues and cell types during development.
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http://dx.doi.org/10.3389/fpls.2019.01434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868056PMC
November 2019

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

Commun Biol 2019 1;2:357. Epub 2019 Oct 1.

1Okinawa Institute of Science and Technology, 1919-1 Tancha Onna-son, 904-0495 Okinawa, Japan.

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 . These genomes were closely related, with 99.7% sequence identity. Among the 9,628 orthologous genes, 4.8% showed signs of positive selection in at least one species. Divergent selective trajectories were discovered in conserved chemosensory gene families (IGR, SNMP), and Halloween genes (CYP) involved in moulting and reproduction. However, there was little overlap in these gene sets and associated GO terms, indicating different selective regimes operating on each of the parasites. Based on our findings, we suggest that species-specific strategies may be needed to combat evolving parasite communities.
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http://dx.doi.org/10.1038/s42003-019-0606-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773775PMC
May 2020

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

Genome Biol 2019 08 2;20(1):153. Epub 2019 Aug 2.

USDA-ARS U.S. Meat Animal Research Center, Clay Center, NE, 68933, USA.

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. We demonstrate novel techniques that work synergistically to improve characterization of biological features in a highly complex rumen microbial community.
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http://dx.doi.org/10.1186/s13059-019-1760-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6676630PMC
August 2019

Linking the resistome and plasmidome to the microbiome.

ISME J 2019 10 30;13(10):2437-2446. Epub 2019 May 30.

Department of Biological Sciences, University of Idaho, Moscow, ID, 83844, USA.

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. Here we demonstrate that the in vivo proximity-ligation method Hi-C can reconstruct a known plasmid-host association from a wastewater community, and identify the in situ host range of ARGs, plasmids, and integrons by physically linking them to their host chromosomes. Hi-C detected both previously known and novel associations between ARGs, mobile genetic elements and host genomes, thus validating this method. We showed that IncQ plasmids and class 1 integrons had the broadest host range in this wastewater, and identified bacteria belonging to Moraxellaceae, Bacteroides, and Prevotella, and especially Aeromonadaceae as the most likely reservoirs of ARGs in this community. A better identification of the natural carriers of ARGs will aid the development of strategies to limit resistance spread to pathogens.
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http://dx.doi.org/10.1038/s41396-019-0446-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776055PMC
October 2019

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

J Am Soc Nephrol 2019 Feb 13. Epub 2019 Feb 13.

Department of Anatomic Pathology,

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.

Methods: We generated regulatory DNA maps (DNase-seq) and paired gene expression profiles (RNA-seq) from primary outgrowth cultures of human glomeruli that were composed mainly of podocytes and mesangial cells. We generated similar datasets from renal cortex cultures, to compare with those of the glomerular cultures. Because regulatory DNA elements can act on target genes across large genomic distances, we also generated a chromatin conformation map from freshly isolated human glomeruli.

Results: We identified thousands of unique regulatory DNA elements, many located close to transcription factor genes, which the glomerular and cortex samples expressed at different levels. We found that genetic variants associated with kidney diseases (GWAS) and kidney expression quantitative trait loci were enriched in regulatory DNA regions. By combining GWAS, epigenomic, and chromatin conformation data, we functionally annotated 46 kidney disease genes.

Conclusions: We demonstrate a powerful approach to functionally connect kidney disease-/trait-associated loci to their target genes by leveraging unique regulatory DNA maps and integrated epigenomic and genetic analysis. This process can be applied to other kidney cell types and will enhance our understanding of genome regulation and its effects on gene expression in kidney disease.
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http://dx.doi.org/10.1681/ASN.2018030309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405142PMC
February 2019

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

BMC Genomics 2019 Feb 7;20(1):120. Epub 2019 Feb 7.

Department of Plant and Microbial Biology, University of Minnesota, St. Paul, MN, USA.

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.

Results: In order to address the role of genome architecture and chromosome scale structural variation in generating diversity of SMBGCs, we generated chromosome scale assemblies of six geographically diverse isolates of the insect pathogenic fungus Tolypocladium inflatum, producer of the multi-billion dollar lifesaving immunosuppressant drug cyclosporin, and utilized a Hi-C chromosome conformation capture approach to address the role of genome architecture and structural variation in generating intraspecific diversity in SMBGCs. Our results demonstrate that the exchange of DNA between heterologous chromosomes plays an important role in generating novelty in SMBGCs in fungi. In particular, we demonstrate movement of a polyketide synthase (PKS) and several adjacent genes by translocation to a new chromosome and genomic context, potentially generating a novel PKS cluster. We also provide evidence for inter-chromosomal recombination between nonribosomal peptide synthetases located within subtelomeres and uncover a polymorphic cluster present in only two strains that is closely related to the cluster responsible for biosynthesis of the mycotoxin aflatoxin (AF), a highly carcinogenic compound that is a major public health concern worldwide. In contrast, the cyclosporin cluster, located internally on chromosomes, was conserved across strains, suggesting selective maintenance of this important virulence factor for infection of insects.

Conclusions: This research places the evolution of SMBGCs within the context of whole genome evolution and suggests a role for recombination between chromosomes in generating novel SMBGCs in the medicinal fungus Tolypocladium inflatum.
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http://dx.doi.org/10.1186/s12864-018-5399-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6367777PMC
February 2019

A near complete, chromosome-scale assembly of the black raspberry (Rubus occidentalis) genome.

Gigascience 2018 08 1;7(8). Epub 2018 Aug 1.

USDA-ARS National Clonal Germplasm Repository, 33447 Peoria Rd., Corvallis, OR, 97333, USA.

Background: The fragmented nature of most draft plant genomes has hindered downstream gene discovery, trait mapping for breeding, and other functional genomics applications. There is a pressing need to improve or finish draft plant genome assemblies.

Findings: Here, we present a chromosome-scale assembly of the black raspberry genome using single-molecule real-time Pacific Biosciences sequencing and high-throughput chromatin conformation capture (Hi-C) genome scaffolding. The updated V3 assembly has a contig N50 of 5.1 Mb, representing an ∼200-fold improvement over the previous Illumina-based version. Each of the 235 contigs was anchored and oriented into seven chromosomes, correcting several major misassemblies. Black raspberry V3 contains 47 Mb of new sequences including large pericentromeric regions and thousands of previously unannotated protein-coding genes. Among the new genes are hundreds of expanded tandem gene arrays that were collapsed in the Illumina-based assembly. Detailed comparative genomics with the high-quality V4 woodland strawberry genome (Fragaria vesca) revealed near-perfect 1:1 synteny with dramatic divergence in tandem gene array composition. Lineage-specific tandem gene arrays in black raspberry are related to agronomic traits such as disease resistance and secondary metabolite biosynthesis.

Conclusions: The improved resolution of tandem gene arrays highlights the need to reassemble these highly complex and biologically important regions in draft plant genomes. The updated, high-quality black raspberry reference genome will be useful for comparative genomics across the horticulturally important Rosaceae family and enable the development of marker assisted breeding in Rubus.
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http://dx.doi.org/10.1093/gigascience/giy094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131213PMC
August 2018

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

Hortic Res 2018 7;5. Epub 2018 Feb 7.

The New Zealand Institute for Plant & Food Research Limited, Private Bag 11600, Palmerston North, 4474 New Zealand.

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. The recently released draft genome for black raspberry (ORUS 4115-3) lacks assembly of scaffolds to chromosome scale. We used high-throughput chromatin conformation capture (Hi-C) and Proximity-Guided Assembly (PGA) to cluster and order 9650 out of 11,936 contigs of this draft genome assembly into seven pseudo-chromosomes. The seven pseudo-chromosomes cover ~97.2% of the total contig length (~223.8 Mb). Locating existing genetic markers on the physical map resolved multiple discrepancies in marker order on the genetic map. Centromeric regions were inferred from recombination frequencies of genetic markers, alignment of 303 bp centromeric sequence with the PGA, and heat map showing the physical contact matrix over the entire genome. We demonstrate a high degree of synteny between each of the seven chromosomes of black raspberry and a high-quality reference genome for strawberry ( L.) assembled using only PacBio long-read sequences. We conclude that PGA is a cost-effective and rapid method of generating chromosome-scale assemblies from Illumina short-read sequencing data.
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http://dx.doi.org/10.1038/s41438-017-0013-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802725PMC
February 2018

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

J Hered 2017 Sep;108(6):693-700

Department of Genetics, University of Georgia, 120 Green Street, Athens, GA 30602

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. Here, we first test the ability of a Hi-C based proximity-guided assembly (PGA) to perform a de novo genome assembly from relatively short contigs. Using Hi-C based PGA, we generated complete chromosome assemblies from a distribution of short contigs (20-100 kb). We found that 96.40% of contigs were correctly assigned to linkage groups (LGs), with ordering nearly identical to the previous genome assembly. Using available bacterial artificial chromosome (BAC) end sequences, we provide evidence that some of the few discrepancies between the Hi-C assembly and the existing assembly are due to structural variation between the populations used for the 2 assemblies or errors in the existing assembly. This Hi-C assembly also allowed us to improve the existing assembly, assigning over 60% (13.35 Mb) of the previously unassigned (~21.7 Mb) contigs to LGs. Together, our results highlight the potential of the Hi-C based PGA method to be used in combination with short read data to perform relatively inexpensive de novo genome assemblies. This approach will be particularly useful in organisms in which it is difficult to perform linkage mapping or to obtain high molecular weight DNA required for other scaffolding methods.
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http://dx.doi.org/10.1093/jhered/esx058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892396PMC
September 2017

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

Nat Genet 2017 Apr 6;49(4):643-650. Epub 2017 Mar 6.

US Meat Animal Research Center, ARS USDA, Clay Center, Nebraska, USA.

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. These combined technologies produced what is, to our knowledge, the most continuous de novo mammalian assembly to date, with chromosome-length scaffolds and only 649 gaps. Our assembly represents a ∼400-fold improvement in continuity due to properly assembled gaps, compared to the previously published C. hircus assembly, and better resolves repetitive structures longer than 1 kb, representing the largest repeat family and immune gene complex yet produced for an individual of a ruminant species.
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http://dx.doi.org/10.1038/ng.3802DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5909822PMC
April 2017

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

Cell Rep 2014 Sep 15;8(6):2015-2030. Epub 2014 Sep 15.

Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address:

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. We show that variation associated with 72 diverse quantitative phenotypes localizes within DHSs. TF footprints encode an extensive cis-regulatory lexicon subject to recent evolutionary pressures, and widespread TF binding within exons may have shaped codon usage patterns. The architecture of A. thaliana TF regulatory networks is strikingly similar to that of animals in spite of diverged regulatory repertoires. We analyzed regulatory landscape dynamics during heat shock and photomorphogenesis, disclosing thousands of environmentally sensitive elements and enabling mapping of key TF regulatory circuits underlying these fundamental responses. Our results provide an extensive resource for the study of A. thaliana gene regulation and functional biology.
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http://dx.doi.org/10.1016/j.celrep.2014.08.019DOI Listing
September 2014

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

Annu Int Conf IEEE Eng Med Biol Soc 2011 ;2011:4745-8

Kimberly-Clark Corporation, Neenah, WI 54956, USA.

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. Unobtrusive non-contact monitoring can be the only realistic solution for long term home-based sleep monitoring. The demand for a low-cost and non-invasive sleep monitoring system for in-home use is more than before due to an increasingly stressful life style. Cost and complexity of current sensor elements hinder the development of low-cost sleep monitoring devices for in-home use. This paper presents the design, development and implementation of a low-cost and disposable pressure sensor mat that could be useful for in-home sleep and movement monitoring applications. The sensor mat design is based on a compressible foam sandwiched between two orthogonal arrays of cPaper capacitance sensors. A low-cost conducting paper has been developed for use as the capacitance sensor electrode. Typical mat design uses a 3 mm thick foam with 5 mm row/column grid array shows that it has a measurement resolution of 0.1 PSI pressure. The resolution can be controlled by both modifying properties of the conducting paper and the foam. Since this pressure mat design is based on low-cost paper, the sensor electrodes are disposable or semi-durable and hence it is ideal for the use in point-of-care physiological monitoring, pervasive healthcare and consumer electronic devices.
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http://dx.doi.org/10.1109/IEMBS.2011.6091175DOI Listing
July 2012

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

Nat Genet 2010 May 28;42(5):392-9. Epub 2010 Mar 28.

ALS Therapy Development Institute, Cambridge, Massachusetts, USA.

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. A therapy using a monoclonal antibody to CD40L was developed that slows weight loss, delays paralysis and extends survival in an ALS mouse model. This work demonstrates that unbiased transcript profiling can identify cellular pathways responsive to therapeutic intervention in a preclinical model of human disease.
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http://dx.doi.org/10.1038/ng.557DOI Listing
May 2010

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

Langmuir 2005 Feb;21(4):1322-7

Department of Chemistry & Biochemistry, and University of Delaware Surface Analysis Facility, University of Delaware, Newark, Delaware 19716, USA.

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. The polymerization could be confined to certain nanometer-sized areas by using "molecule corrals,"and polymerization appeared to be governed by topochemical constraints. Polymerization across domain boundaries, or over molecule corral edges, was never observed in over approximately 150 observations. Due to the constant supply of nonpolymerized molecules from the covering solution, a dynamic exchange between molecules on the surface and in the solution was possible. This exchange occurred on a time scale that was comparable to the image acquisition time (approximately 10(1) s), and appeared to depend weakly upon the length of the desorbing oligomer. The desorption process was probably also influenced by interactions with the STM tip.
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http://dx.doi.org/10.1021/la048586gDOI Listing
February 2005

Plant genetic resources and the law: past, present, and future.

Authors:
Shawn N Sullivan

Plant Physiol 2004 May;135(1):10-5

Intellectual Property Counsel, Centro Internacional de Mejoramiento de Maíz y Trigo, Apartado Postal 6-641 06600 Mexico, DF, Mexico.

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http://dx.doi.org/10.1104/pp.104.042572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC429328PMC
May 2004