Proposals for Addressing Exotic Invasive Species: The Middle Patuxent Environmental Area and Surrounds

Final project for LARC452: Green Infrastructure & Community Greening (Fall 2015). Department of Plant Science and Landscape Architecture, University of Maryland, College Park.This report describes efforts undertaken by students as part of LARC 452 Green Infrastructure and Community Greening, Fall 2015. The course is divided into three sections. Section one focuses on land preservation principles and programs in the State of Maryland. Section two focuses on greening standards in the site development process including the implementation of the Maryland Forest Conservation Act and the District’s Green Area Ratio. Section three focuses on green interventions related to stormwater efforts and the implementation of Maryland ESD requirements. This research served as the project for the primarily lecture- based course. This research served two purposes for the overall course. First, it provided students with the opportunity to review and propose solutions to practical, real world invasive species issues. Secondly, the two field trips allowed students, particularly those with minimal vegetation or plant science background, real field experiences and the opportunity to learn from Howard County staff and other students. This was a valuable experience. The overall document provides three primary outcomes. The results of the field days provided data from sampling of 20 permanent vegetation plots in the northern section of Northern Conservation Area. The Northern Conservation Area has approximately 34 plots. Invasive species occurred in 100% of the 20 plots. The most prevalent species were Lonicera japonica, Microstegium vimineum, and Rosa multiflora. The second outcome is a series of proposals for addressing invasive species. The proposals draw on the adjacent land uses—schools, golf course and residential. The third outcome is a compilation of reference annotations that were investigated to support the development of the proposals. In the discussion of invasive species, students gained an acute and tangible understanding of the problem of invasive species and the challenges of addressing this widespread problem. The proposals reflect a consensus that public-private partnerships supported by both public and private leadership are needed to address the quality of forest environments and a difficult problem such as invasive species.Howard Count

Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals

Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up

CycleTalk: Towards a Dialogue Agent that Guides Design with an Articulate Simulator

Abstract. We discuss the motivation for a novel style of tutorial dialogue system that emphasizes reflection in a design context. Our current research focuses on the hypothesis that this type of dialogue will lead to better learning than previous tutorial dialogue systems because (1) it motivates students to explain more in order to justify their thinking, and (2) it supports students’ meta-cognitive ability to ask themselves good questions about the design choices they make. We present a preliminary cognitive task analysis of design exploration tasks using CyclePad, an articulate thermodynamics simulator [10]. Using this cognitive task analysis, we analyze data collected in two initial studies of students using CyclePad, one in an unguided manner, and one in a Wizard of Oz scenario. This analysis suggests ways in which tutorial dialogue can be used to assist students in their exploration and encourage a fruitful learning orientation. Finally, we conclude with some system desiderata derived from our analysis as well as plans for further exploration.

Nonstructural Protein σ1s Is a Determinant of Reovirus Virulence and Influences the Kinetics and Severity of Apoptosis Induction in the Heart and Central Nervous System

The mechanisms by which viruses kill susceptible cells in target organs and ultimately produce disease in the infected host remain poorly understood. Dependent upon the site of inoculation and strain of virus, experimental infection of neonatal mice with reoviruses can induce fatal encephalitis or myocarditis. Reovirus-induced apoptosis is a major mechanism of tissue injury, leading to disease development in both the brain and heart. In cultured cells, differences in the capacity of reovirus strains to induce apoptosis are determined by the S1 gene segment, which also plays a major role as a determinant of viral pathogenesis in both the heart and the central nervous system (CNS) in vivo. The S1 gene is bicistronic, encoding both the viral attachment protein sigma-1 and the nonstructural protein sigma-1-small (σ1s). Although σ1s is dispensable for viral replication in vitro, we wished to investigate the expression of σ1s in the infected heart and brain and its potential role in reovirus pathogenesis in vivo. Two-day-old mice were inoculated intramuscularly or intracerebrally with either σ1s(−) or σ1s(+) reovirus strains. While viral replication in target organs did not differ between σ1s(−) and σ1s(+) viral strains, virus-induced caspase-3 activation and resultant histological tissue injury in both the heart and brain were significantly reduced in σ1s(−) reovirus-infected animals. These results demonstrate that σ1s is a determinant of the magnitude and extent of reovirus-induced apoptosis in both the heart and CNS and thereby contributes to reovirus pathogenesis and virulence

Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals

Genes underneath signals from genome-wide association studies (GWAS) for kidney function are promising targets for functional studies, but prioritizing variants and genes is challenging. By GWAS meta-analysis for creatinine-based estimated glomerular filtration rate (eGFR) from the Chronic Kidney Disease Genetics Consortium and UK Biobank (n = 1,201,909), we expand the number of eGFRcrea loci (424 loci, 201 novel; 9.8% eGFRcrea variance explained by 634 independent signal variants). Our increased sample size in fine-mapping (n = 1,004,040, European) more than doubles the number of signals with resolved fine-mapping (99% credible sets down to 1 variant for 44 signals, ≤5 variants for 138 signals). Cystatin-based eGFR and/or blood urea nitrogen association support 348 loci (n = 460,826 and 852,678, respectively). Our customizable tool for Gene PrioritiSation reveals 23 compelling genes including mechanistic insights and enables navigation through genes and variants likely relevant for kidney function in human to help select targets for experimental follow-up

The completion of the Mammalian Gene Collection

Since its start, the Mammalian Gene Collection (MGC) has sought to provide at least one full-protein-coding sequence cDNA clone for every human and mouse gene with a RefSeq transcript, and at least 6200 rat genes. The MGC cloning effort initially relied on random expressed sequence tag screening of cDNA libraries. Here, we summarize our recent progress using directed RT-PCR cloning and DNA synthesis. The MGC now contains clones with the entire protein-coding sequence for 92% of human and 89% of mouse genes with curated RefSeq (NM-accession) transcripts, and for 97% of human and 96% of mouse genes with curated RefSeq transcripts that have one or more PubMed publications, in addition to clones for more than 6300 rat genes. These high-quality MGC clones and their sequences are accessible without restriction to researchers worldwide

Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease

Background Plasma triglyceride levels are heritable and are correlated with the risk of coronary heart disease. Sequencing of the protein-coding regions of the human genome (the exome) has the potential to identify rare mutations that have a large effect on phenotype. Methods We sequenced the protein-coding regions of 18,666 genes in each of 3734 participants of European or African ancestry in the Exome Sequencing Project. We conducted tests to determine whether rare mutations in coding sequence, individually or in aggregate within a gene, were associated with plasma triglyceride levels. For mutations associated with triglyceride levels, we subsequently evaluated their association with the risk of coronary heart disease in 110,970 persons. Results An aggregate of rare mutations in the gene encoding apolipoprotein C3 (APOC3) was associated with lower plasma triglyceride levels. Among the four mutations that drove this result, three were loss-of-function mutations: a nonsense mutation (R19X) and two splice-site mutations (IVS2+1G -> A and IVS3+1G -> T). The fourth was a missense mutation (A43T). Approximately 1 in 150 persons in the study was a heterozygous carrier of at least one of these four mutations. Triglyceride levels in the carriers were 39% lower than levels in noncarriers (P<1x10(-20)), and circulating levels of APOC3 in carriers were 46% lower than levels in noncarriers (P = 8x10(-10)). The risk of coronary heart disease among 498 carriers of any rare APOC3 mutation was 40% lower than the risk among 110,472 noncarriers (odds ratio, 0.60; 95% confidence interval, 0.47 to 0.75; P = 4x10(-6)). Conclusions Rare mutations that disrupt APOC3 function were associated with lower levels of plasma triglycerides and APOC3. Carriers of these mutations were found to have a reduced risk of coronary heart disease. (Funded by the National Heart, Lung, and Blood Institute and others.