Genome-wide association study of leaf architecture in the maize nested association mapping population

US maize yield has increased eight-fold in the past 80 years, with half of the gain attributed to selection by breeders. During this time, changes in maize leaf angle and size have altered plant architecture, allowing more efficient light capture as planting density has increased. Through a genome-wide association study (GWAS) of the maize nested association mapping panel, we determined the genetic basis of important leaf architecture traits and identified some of the key genes. Overall, we demonstrate that the genetic architecture of the leaf traits is dominated by small effects, with little epistasis, environmental interaction or pleiotropy. In particular, GWAS results show that variations at the liguleless genes have contributed to more upright leaves. These results demonstrate that the use of GWAS with specially designed mapping populations is effective in uncovering the basis of key agronomic traits.     

Conventionalism in Reid’s ‘geometry of visibles’

The subject of this investigation is the role of conventions in the formulation of Thomas Reid’s theory of the geometry of vision, which he calls the ‘geometry of visibles’. In particular, we will examine the work of N. Daniels and R. Angell who have alleged that, respectively, Reid’s ‘geometry of visibles’ and the geometry of the visual field are non-Euclidean. As will be demonstrated, however, the construction of any geometry of vision is subject to a choice of conventions regarding the construction and assignment of its various properties, especially metric properties, and this fact undermines the claim for a unique non-Euclidean status for the geometry of vision. Finally, a suggestion is offered for trying to reconcile Reid’s direct realist theory of perception with his geometry of visibles.While Thomas Reid is well-known as the leading exponent of the Scottish ‘common-sense’ school of philosophy, his role in the history of geometry has only recently been drawing the attention of the scholarly community. In particular, several influential works, by N. Daniels and R. B. Angell, have claimed Reid as the discoverer of non-Euclidean geometry; an achievement, moreover, that pre-dates the geometries of Lobachevsky, Bolyai, and Gauss by over a half century. Reid’s alleged discovery appears within the context of his analysis of the geometry of the visual field, which he dubs the ‘geometry of visibles’. In summarizing the importance of Reid’s philosophy in this area, Daniels is led to conclude that ‘there can remain little doubt that Reid intends the geometry of visibles to be an alternative to Euclidean geometry’;¹ while Angell, similarly inspired by Reid, draws a much stronger inference: ‘The geometry which precisely and naturally fits the actual configurations of the visual field is a non-Euclidean, two-dimensional, elliptical geometry. In substance, this thesis was advanced by Thomas Reid in 1764 ...’² The significance of these findings has not gone unnoticed in mathematical and scientific circles, moreover, for Reid’s name is beginning to appear more frequently in historical surveys of the development of geometry and the theories of space.³Implicit in the recent work on Reid’s ‘geometry of visibles’, or GOV, one can discern two closely related but distinct arguments: first, that Reid did in fact formulate a non-Euclidean geometry, and second, that the GOV is non-Euclidean. This essay will investigate mainly the latter claim, although a lengthy discussion will be accorded to the first. Overall, in contrast to the optimistic reports of a non-Euclidean GOV, it will be argued that there is a great deal of conceptual freedom in the construction of any geometry pertaining to the visual field. Rather than single out a non-Euclidean structure as the only geometry consistent with visual phenomena, an examination of Reid, Daniels, and Angell will reveal the crucial role of geometric ‘conventions’, especially of the metric sort, in the formulation of the GOV (where a ‘metric’ can be simply defined as a system for determining distances, the measures of angles, etc.). Consequently, while a non-Euclidean geometry is consistent with Reid’s GOV, it is only one of many different geometrical structures that a GOV can possess. Angell’s theory that the GOV can only be construed as non-Euclidean, is thus incorrect. After an exploration of Reid’s theory and the alleged non-Euclidean nature of the GOV, in 1 and 2 respectively, the focus will turn to the tacit role of conventionalism in Daniels’ reconstruction of Reid’s GOV argument, and in the contemporary treatment of a non-Euclidean visual geometry offered by Angell ( 3 and 4). Finally, in the conclusion, a suggestion will be offered for a possible reconstruction of Reid’s GOV that does not violate his avowed ‘direct realist’ theory of perception, since this epistemological thesis largely prompted his formulation of the GOV.     

A Gata6-Wnt pathway required for epithelial stem cell development and airway regeneration

Epithelial organs, including the lung, are known to possess regenerative abilities through activation of endogenous stem cell populations, but the molecular pathways regulating stem cell expansion and regeneration are not well understood. Here we show that Gata6 regulates the temporal appearance and number of bronchioalveolar stem cells (BASCs) in the lung, its absence in Gata6-null lung epithelium leading to the precocious appearance of BASCs and concurrent loss in epithelial differentiation. This expansion of BASCs was the result of a pronounced increase in canonical Wnt signaling in lung epithelium upon loss of Gata6. Expression of the noncanonical Wnt receptor Fzd2 was downregulated in Gata6 mutants and increased Fzd2 or decreased beta-catenin expression rescued, in part, the lung epithelial defects in Gata6 mutants. During lung epithelial regeneration, canonical Wnt signaling was activated in the niche containing BASCs and forced activation of Wnt signaling led to a large increase in BASC numbers. Moreover, Gata6 was required for proper lung epithelial regeneration, and postnatal loss of Gata6 led to increased BASC expansion and decreased differentiation. Together, these data demonstrate that Gata6-regulated Wnt signaling controls the balance between progenitor expansion and epithelial differentiation required for both lung development and regeneration.     

Primary structure of Torpedo californica acetylcholinesterase deduced from its cDNA sequence

Acetylcholinesterase, an essential enzyme of the nervous system, rapidly terminates the action of acetylcholine released into the synapse. Acetylcholinesterase is also found (in lower abundance) in extrajunctional areas of muscle and nerve and on erythrocyte membranes. Hydrodynamic analyses of the native enzyme and characterization of its dissociated subunits have revealed multiple enzyme forms which can be divided into two classes: dimensionally asymmetric forms which are usually found within the synapse and contain a collagen-like structural subunit disulphide-linked to the catalytic subunits; and globular forms which appear to be widely distributed on the outer surface of cell membranes. Both forms have been characterized in the ray Torpedo californica and, although their catalytic behaviours seem to be identical, they differ slightly in amino-acid composition, peptide maps and reactivity with certain monoclonal antibodies. Here, we report the complete amino-acid sequence of an acetylcholinesterase inferred from the sequence of a complementary DNA clone. The 575-residue protein shows significant homology with the C-terminal portion of thyroglobulin.     

The accuracy of extrapolation (time series) methods: Results of a forecasting competition

In the last few decades many methods have become available for forecasting. As always, when alternatives exist, choices need to be made so that an appropriate forecasting method can be selected and used for the specific situation being considered. This paper reports the results of a forecasting competition that provides information to facilitate such choice. Seven experts in each of the 24 methods forecasted up to 1001 series for six up to eighteen time horizons. The results of the competition are presented in this paper whose purpose is to provide empirical evidence about differences found to exist among the various extrapolative (time series) methods used in the competition.     

The Ter mutation in the dead end gene causes germ cell loss and testicular germ cell tumours

In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine to uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.     

An autoregulatory circuit for long-range self-organization in Dictyostelium cell populations

Nutrient-deprived Dictyostelium amoebae aggregate to form a multicellular structure by chemotaxis, moving towards propagating waves of cyclic AMP that are relayed from cell to cell. Organizing centres are not formed by founder cells, but are dynamic entities consisting of cores of outwardly rotating spiral waves that self-organize in a homogeneous cell population. Spiral waves are ubiquitously observed in chemical reactions as well as in biological systems. Although feedback control of spiral waves in spatially extended chemical reactions has been demonstrated in recent years, the mechanism by which control is achieved in living systems is unknown. Here we show that mutants of the cyclic AMP/protein kinase A pathway show periodic signalling, but fail to organize coherent long-range wave territories, owing to the appearance of numerous spiral cores. A theoretical model suggests that autoregulation of cell excitability mediated by protein kinase A acts to optimize the number of signalling centres.     

Generation and annotation of the DNA sequences of human chromosomes 2 and 4

Human chromosome 2 is unique to the human lineage in being the product of a head-to-head fusion of two intermediate-sized ancestral chromosomes. Chromosome 4 has received attention primarily related to the search for the Huntington's disease gene, but also for genes associated with Wolf-Hirschhorn syndrome, polycystic kidney disease and a form of muscular dystrophy. Here we present approximately 237 million base pairs of sequence for chromosome 2, and 186 million base pairs for chromosome 4, representing more than 99.6% of their euchromatic sequences. Our initial analyses have identified 1,346 protein-coding genes and 1,239 pseudogenes on chromosome 2, and 796 protein-coding genes and 778 pseudogenes on chromosome 4. Extensive analyses confirm the underlying construction of the sequence, and expand our understanding of the structure and evolution of mammalian chromosomes, including gene deserts, segmental duplications and highly variant regions.