A Summary of Archaeological Excavations from 1983-1986 at the Green Family Print Shop, 18AP29, Annapolis, Maryland

18AP29, the Green Family Printshop, also known as the Jonas Green site, was excavated from 1983 to 1986 by Archaeology in Annapolis and Historic Annapolis Foundation. The site is not only the home of a significant figure in colonial Maryland but is also the location of one of the first colonial printing operations in Maryland. This site represents an important pre-industrial business in Annapolis. While this domestic site is complicated and rich, one of the most fascinating aspect of 18AP29 is the discovery of a large quantity of printers' type. Extensive analysis of the printers' type and documentary research on one of the print shop's products, the colonial newspaper, the Maryland Gazette, provides insights into the print culture which was developing during the 18th and 19th centuries. This report summarizes the stratigraphic analysis, minimum vessel counts, and faunal analysis. It provides some description of the printers' type

Panzea: a database and resource for molecular and functional diversity in the maize genome

Serving as a community resource, Panzea () is the bioinformatics arm of the Molecular and Functional Diversity in the Maize Genome project. Maize, a classical model for genetic studies, is an important crop species and also the most diverse crop species known. On average, two randomly chosen maize lines have one single-nucleotide polymorphism every ∼100 bp; this divergence is roughly equivalent to the differences between humans and chimpanzees. This exceptional genotypic diversity underlies the phenotypic diversity maize needs to be cultivated in a wide range of environments. The Molecular and Functional Diversity in the Maize Genome project aims to understand how selection has shaped molecular diversity in maize and then relate molecular diversity to functional phenotypic variation. The project will screen 4000 loci for the signature of selection and create a wide range of maize and maize–teosinte mapping populations. These populations will be genotyped and phenotyped, permitting high-power and high-resolution dissection of the traits and relating the molecular diversity to functional variation. Panzea provides access to the genotype, phenotype and polymorphism data produced by the project through user-friendly web-based database searches and data retrieval/visualization tools, as well as a wide variety of information and services related to maize diversity

Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor)

Sorghum (Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ∼5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ∼33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles

The scale of population structure in Arabidopsis thaliana

The population structure of an organism reflects its evolutionary history and influences its evolutionary trajectory. It constrains the combination of genetic diversity and reveals patterns of past gene flow. Understanding it is a prerequisite for detecting genomic regions under selection, predicting the effect of population disturbances, or modeling gene flow. This paper examines the detailed global population structure of Arabidopsis thaliana. Using a set of 5,707 plants collected from around the globe and genotyped at 149 SNPs, we show that while A. thaliana as a species self-fertilizes 97% of the time, there is considerable variation among local groups. This level of outcrossing greatly limits observed heterozygosity but is sufficient to generate considerable local haplotypic diversity. We also find that in its native Eurasian range A. thaliana exhibits continuous isolation by distance at every geographic scale without natural breaks corresponding to classical notions of populations. By contrast, in North America, where it exists as an exotic species, A. thaliana exhibits little or no population structure at a continental scale but local isolation by distance that extends hundreds of km. This suggests a pattern for the development of isolation by distance that can establish itself shortly after an organism fills a new habitat range. It also raises questions about the general applicability of many standard population genetics models. Any model based on discrete clusters of interchangeable individuals will be an uneasy fit to organisms like A. thaliana which exhibit continuous isolation by distance on many scales

Quantitative imaging biomarkers of coronary plaque morphology: insights from EVAPORATE

AimsResidual cardiovascular risk persists despite statin therapy. In REDUCE-IT, icosapent ethyl (IPE) reduced total events, but the mechanisms of benefit are not fully understood. EVAPORATE evaluated the effects of IPE on plaque characteristics by coronary computed tomography angiography (CCTA). Given the conclusion that the IPE-treated patients demonstrate that plaque burden decreases has already been published in the primary study analysis, we aimed to demonstrate whether the use of an analytic technique defined and validated in histological terms could extend the primary study in terms of whether such changes could be reliably seen in less time on drug, at the individual (rather than only at the cohort) level, or both, as neither of these were established by the primary study result.Methods and ResultsEVAPORATE randomized the patients to IPE 4 g/day or placebo. Plaque morphology, including lipid-rich necrotic core (LRNC), fibrous cap thickness, and intraplaque hemorrhage (IPH), was assessed using the ElucidVivo® (Elucid Bioimaging Inc.) on CCTA. The changes in plaque morphology between the treatment groups were analyzed. A neural network to predict treatment assignment was used to infer patient representation that encodes significant morphological changes. Fifty-five patients completed the 18-month visit in EVAPORATE with interpretable images at each of the three time points. The decrease of LRNC between the patients on IPE vs. placebo at 9 months (reduction of 2 mm3 vs. an increase of 41 mm3, p = 0.008), widening at 18 months (6 mm3 vs. 58 mm3 increase, p = 0.015) were observed. While not statistically significant on a univariable basis, reductions in wall thickness and increases in cap thickness motivated multivariable modeling on an individual patient basis. The per-patient response assessment was possible using a multivariable model of lipid-rich phenotype at the 9-month follow-up, p < 0.01 (sustained at 18 months), generalizing well to a validation cohort.ConclusionPlaques in the IPE-treated patients acquired more characteristics of stability. Reliable assessment using histologically validated analysis of individual response is possible at 9 months, with sustained stabilization at 18 months, providing a quantitative basis to elucidate drug mechanism and assess individual patient response

Domestication reshaped the genetic basis of inbreeding depression in a maize landrace compared to its wild relative, teosinte

Inbreeding depression is the reduction in fitness and vigor resulting from mating of close relatives observed in many plant and animal species. The extent to which the genetic load of mutations contributing to inbreeding depression is due to large-effect mutations versus variants with very small individual effects is unknown and may be affected by population history. We compared the effects of outcrossing and self-fertilization on 18 traits in a landrace population of maize, which underwent a population bottleneck during domestication, and a neighboring population of its wild relative teosinte. Inbreeding depression was greater in maize than teosinte for 15 of 18 traits, congruent with the greater segregating genetic load in the maize population that we predicted from sequence data. Parental breeding values were highly consistent between outcross and selfed offspring, indicating that additive effects determine most of the genetic value even in the presence of strong inbreeding depression. We developed a novel linkage scan to identify quantitative trait loci (QTL) representing large-effect rare variants carried by only a single parent, which were more important in teosinte than maize. Teosinte also carried more putative juvenile-acting lethal variants identified by segregation distortion. These results suggest a mixture of mostly polygenic, smalleffect partially recessive effects in linkage disequilibrium underlying inbreeding depression, with an additional contribution from rare larger-effect variants that was more important in teosinte but depleted in maize following the domestication bottleneck. Purging associated with the maize domestication bottleneck may have selected against some large effect variants, but polygenic load is harder to purge and overall segregating mutational burden increased in maize compared to teosinte

Enhancement of CD8 T-cell function through modifying surface glycoproteins in young and old mice

Previous work from our laboratory has shown that modifying cell surface glycosylation with either a Clostridium perfringens -derived sialidase (CP-Siase), or an O-linked glycoprotein endopeptidase (OSGE) can enhance the function of CD4 T cells from both young and old mice at multiple levels. Here we have re-assessed the effect of age on CD8 T-cell function, and examined the outcome of enzymatic treatment with CP-Siase and OSGE on its different aspects. Pre-treatment of CD8 T cells with either CP-Siase or OSGE led to a significant increase in anti-CD3-mediated Ca 2+ response in both young and old mice. Pre-treated CD8 T cells from both age groups also displayed a significant increase in activation-induced CD69 and CD25 expression, and produced significantly higher amounts of interleukin-2 and interferon-γ in comparison to their untreated counterparts. Furthermore, pretreatment with either enzyme enhanced granzyme B expression in CD8 T cells, and increased their cytolytic activity in vitro . These data support the notion that glycosylated surface proteins hinder CD8 T-cell activation and function in both young and old mice, and raise the possibility of significantly improving CD8 T cell function in older individuals through enzymatic alteration of surface glycoproteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75199/1/j.1365-2567.2006.02420.x.pd

Genomic Prediction in Maize Breeding Populations with Genotyping-by-Sequencing

Genotyping-by-sequencing (GBS) technologies have proven capacity for delivering large numbers of marker genotypes with potentially less ascertainment bias than standard single nucleotide polymorphism (SNP) arrays. Therefore, GBS has become an attractive alternative technology for genomic selection. However, the use of GBS data poses important challenges, and the accuracy of genomic prediction using GBS is currently undergoing investigation in several crops, including maize, wheat, and cassava. The main objective of this study was to evaluate various methods for incorporating GBS information and compare them with pedigree models for predicting genetic values of lines from two maize populations evaluated for different traits measured in different environments (experiments 1 and 2). Given that GBS data come with a large percentage of uncalled genotypes, we evaluated methods using nonimputed, imputed, and GBS-inferred haplotypes of different lengths (short or long). GBS and pedigree data were incorporated into statistical models using either the genomic best linear unbiased predictors (GBLUP) or the reproducing kernel Hilbert spaces (RKHS) regressions, and prediction accuracy was quantified using cross-validation methods. The following results were found: relative to pedigree or marker-only models, there were consistent gains in prediction accuracy by combining pedigree and GBS data; there was increased predictive ability when using imputed or nonimputed GBS data over inferred haplotype in experiment 1, or nonimputed GBS and information-based imputed short and long haplotypes, as compared to the other methods in experiment 2; the level of prediction accuracy achieved using GBS data in experiment 2 is comparable to those reported by previous authors who analyzed this data set using SNP arrays; and GBLUP and RKHS models with pedigree with nonimputed and imputed GBS data provided the best prediction correlations for the three traits in experiment 1, whereas for experiment 2 RKHS provided slightly better prediction than GBLUP for drought-stressed environments, and both models provided similar predictions in well-watered environments