The Genetic Basis of Natural Variation in Seed Size and Seed Number and Their Trade-Off Using Arabidopsis thaliana MAGIC Lines

Offspring number and size are key traits determining an individual’s fitness and a crop’s yield. Yet, extensive natural variation within species is observed for these traits. Such variation is typically explained by trade-offs between fecundity and quality, for which an optimal solution is environmentally dependent. Understanding the genetic basis of seed size and number, as well as any possible genetic constraints preventing the maximization of both, is crucial from both an evolutionary and applied perspective. We investigated the genetic basis of natural variation in seed size and number using a set of Arabidopsis thaliana multiparent advanced generation intercross (MAGIC) lines. We also tested whether life history affects seed size, number, and their trade-off. We found that both seed size and seed number are affected by a large number of mostly nonoverlapping QTL, suggesting that seed size and seed number can evolve independently. The allele that increases seed size at most identified QTL is from the same natural accession, indicating past occurrence of directional selection for seed size. Although a significant trade-off between seed size and number is observed, its expression depends on life-history characteristics, and generally explains little variance. We conclude that the trade-off between seed size and number might have a minor role in explaining the maintenance of variation in seed size and number, and that seed size could be a valid target for selection

2-Chloro-6,6-dimethyl-5,6-dihydro­indazolo[2,3-c]quinazoline

Two independent but virtually identical mol­ecules comprise the asymmetric unit of the title compound, C16H14ClN3. The mol­ecules have a slightly curved shape owing to puckering in the six-membered C4N2 ring; the respective dihedral angles formed between the benzene rings are 12.64 (7) and 11.72 (7)°. In the crystal, layers sustained by a combination of N—H⋯N hydrogen bonding as well as C—H⋯N and C—H⋯π contacts are formed; these stack along [011] and are connected by further C—H⋯π contacts

Pancreatic islet transplantation to treat diabetes - defining molecular tools to select suitable islets [abstract]

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionA complete understanding of pancreatic islet biology is essential to the development of preventive or curative interventions for diabetes. It has been known that subpopulations of islets of different sizes exist; however, whether they are biologically and functionally unique has not been investigated. As an example, our work comparing the biology of large versus small islets isolated from rats showed that small islets were superior to large islets in in vitro function and in transplantation outcomes. These results provided the stimulus for an improved approach to islet transplantation in humans. The work also led to new questions regarding the basic physiology of healthy islets. Through collaboration between our University of Kansas Medical Center and Children's Mercy Hospital teams, we determined that small islets secrete higher amount of insulin in vitro when compared to the large islets. We sought to identify whether the islet subpopulations showed differences at the molecular level and thus we investigated their protein expression profiles using two-dimensional polyacrylamide gel electrophoresis (2D PAGE). We found that the protein repertoire in the small and large islets differed significantly. Specifically, some proteins were found only in one type of islets, small or large, while they were missing or their expression levels were different in the other subpopulation. We identified some of the proteins by liquid chromatography - mass spectrometry. Immunofluorescence performed on small and large islets in pancreatic sections, with antibodies against identified proteins, confirmed that the proteins were present in one subpopulation of islets. Of these proteins, at least one was unique to large islets and can potentially be used as a marker to distinguish in vivo between islets that are high-insulin producers and those that fail to secrete significant amounts in insulin. Our long-term goal is to monitor the fate of the different islet populations during diabetes development. In addition, markers like this can be used to determine the best islet subpopulation for transplantation. The data support our hypothesis that integral differences exist between small and large islets that might determine the islets' unique properties under normal conditions and during the development of diabetes. These differences may also influence islet subpopulation behavior in transplantation affecting the outcome

N-(4-Chloro­phen­yl)-1,1,1-trifluoro-N-(trifluoro­methyl­sulfon­yl)methane­sulfonamide

The title mol­ecule, also called 4-chloro-N,N-bis­(trifluoro­methane­sulfon­yl)aniline, C8H4ClF6NO4S2, has non-crystallographic twofold symmetry with the pseudo-axis aligned along the Cl—C⋯C—N backbone of the mol­ecule: the SO2CF3 residues lie to either side of the benzene ring. In the crystal, the presence of C—H⋯O contacts lead to the formation of a sequence of 12-membered {⋯HC2NSO}2 synthons within a supra­molecular chain aligned along [101]

A Signaling Protease Required for Melanization in Drosophila Affects Resistance and Tolerance of Infections

Organisms evolve two routes to surviving infections—they can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens

Bioinformatics tools and database resources for systems genetics analysis in mice—a short review and an evaluation of future needs

During a meeting of the SYSGENET working group ‘Bioinformatics’, currently available software tools and databases for systems genetics in mice were reviewed and the needs for future developments discussed. The group evaluated interoperability and performed initial feasibility studies. To aid future compatibility of software and exchange of already developed software modules, a strong recommendation was made by the group to integrate HAPPY and R/qtl analysis toolboxes, GeneNetwork and XGAP database platforms, and TIQS and xQTL processing platforms. R should be used as the principal computer language for QTL data analysis in all platforms and a ‘cloud’ should be used for software dissemination to the community. Furthermore, the working group recommended that all data models and software source code should be made visible in public repositories to allow a coordinated effort on the use of common data structures and file formats

Tracing Personalized Health Curves during Infections

By concentrating on the relationship between health and microbe number over the course of infections, most pathogenic and mutualistic infections can be summarized by a small alphabet of curves, which has implications not only for basic research but for how we might treat patients

A Multiparent Advanced Generation Inter-Cross to Fine-Map Quantitative Traits in Arabidopsis thaliana

Identifying natural allelic variation that underlies quantitative trait variation remains a fundamental problem in genetics. Most studies have employed either simple synthetic populations with restricted allelic variation or performed association mapping on a sample of naturally occurring haplotypes. Both of these approaches have some limitations, therefore alternative resources for the genetic dissection of complex traits continue to be sought. Here we describe one such alternative, the Multiparent Advanced Generation Inter-Cross (MAGIC). This approach is expected to improve the precision with which QTL can be mapped, improving the outlook for QTL cloning. Here, we present the first panel of MAGIC lines developed: a set of 527 recombinant inbred lines (RILs) descended from a heterogeneous stock of 19 intermated accessions of the plant Arabidopsis thaliana. These lines and the 19 founders were genotyped with 1,260 single nucleotide polymorphisms and phenotyped for development-related traits. Analytical methods were developed to fine-map quantitative trait loci (QTL) in the MAGIC lines by reconstructing the genome of each line as a mosaic of the founders. We show by simulation that QTL explaining 10% of the phenotypic variance will be detected in most situations with an average mapping error of about 300 kb, and that if the number of lines were doubled the mapping error would be under 200 kb. We also show how the power to detect a QTL and the mapping accuracy vary, depending on QTL location. We demonstrate the utility of this new mapping population by mapping several known QTL with high precision and by finding novel QTL for germination data and bolting time. Our results provide strong support for similar ongoing efforts to produce MAGIC lines in other organisms

Contributions of phonological and verbal working memory to language development in adolescents with fragile X syndrome

Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability. Although language delays are frequently observed in FXS, neither the longitudinal course of language development nor its cognitive predictors are well understood. The present study investigated whether phonological and working memory skills are predictive of growth in vocabulary and syntax in individuals with FXS during adolescence. Forty-four individuals with FXS (mean age = 12.61 years) completed assessments of phonological memory (nonword repetition and forward digit recall), verbal working memory (backward digit recall), vocabulary, syntax, and nonverbal cognition. Vocabulary and syntax skills were reassessed at a 2-year follow-up. In a series of analyses that controlled for nonverbal cognitive ability and severity of autism symptoms, the relative contributions of phonological and working memory to language change over time were investigated. These relationships were examined separately for boys and girls. In boys with FXS, phonological memory significantly predicted gains in vocabulary and syntax skills. Further, verbal working memory was uniquely associated with vocabulary gains among boys. In girls with FXS, phonological and working memory skills showed no relationship with language change across the 2-year time period. Our findings indicate that, for adolescent boys with FXS, acquisition of vocabulary and syntax may be constrained by the ability to maintain and manipulate phonological representations online. Implications for the identification and treatment of language disorders in this population are discussed. The present study is the first to identify specific cognitive mechanisms contributing to language growth over time in individuals with FXS

An experimental study of executive function and social impairment in Cornelia de Lange syndrome

Background Extreme shyness and social anxiety is reported to be characteristic of adolescents and adults with Cornelia de Lange syndrome (CdLS); however, the nature of these characteristics is not well documented. In this study, we develop and apply an experimental assessment of social anxiety in a group of adolescents and adults with CdLS to determine the nature of the social difficulties and whether they are related to impairments in executive functioning. Methods A familiar and unfamiliar examiner separately engaged in socially demanding tasks comprising three experimental conditions with a group of individuals with CdLS (n = 25; % male = 44; mean age = 22.16; SD = 8.81) and a comparable group of individuals with Down syndrome (DS; n = 20; % male = 35; mean age = 24.35; SD = 5.97). Behaviours indicative of social anxiety were coded. The Behavior Rating Inventory of Executive Function-Preschool version, an informant measure of executive function, was completed by participants’ caregivers. Results Significantly less verbalisation was observed in the CdLS group than the DS group in conditions requiring the initiation of speech. In the CdLS group, impairments in verbalisation were not associated with a greater degree of intellectual disability but were significantly correlated with impairments in both planning and working memory. This association was not evident in the DS group. Conclusions Adolescents and adults with CdLS have a specific difficulty with the initiation of speech when social demands are placed upon them. This impairment in verbalisation may be underpinned by specific cognitive deficits, although further research is needed to investigate this fully