Transcription factor redundancy and tissue-specific regulation: Evidence from functional and physical network connectivity

Two major transcriptional regulators of Caenorhabditis elegans bodywall muscle (BWM) differentiation, hlh-1 and unc-120, are expressed in muscle where they are known to bind and regulate several well-studied muscle-specific genes. Simultaneously mutating both factors profoundly inhibits formation of contractile BWM. These observations were consistent with a simple network model in which the muscle regulatory factors drive tissue-specific transcription by binding selectively near muscle-specific targets to activate them. We tested this model by measuring the number, identity, and tissue-specificity of functional regulatory targets for each factor. Some joint regulatory targets (218) are BWM-specific and enriched for nearby HLH-1 binding. However, contrary to the simple model, the majority of genes regulated by one or both muscle factors are also expressed significantly in non-BWM tissues. We also mapped global factor occupancy by HLH-1, and created a genetic interaction map that identifies hlh-1 collaborating transcription factors. HLH-1 binding did not predict proximate regulatory action overall, despite enrichment for binding among BWM-specific positive regulatory targets of hlh-1. We conclude that these tissue-specific factors contribute much more broadly to the transcriptional output of muscle tissue than previously thought, offering a partial explanation for widespread HLH-1 occupancy. We also identify a novel regulatory connection between the BWM-specific hlh-1 network and the hlh-8/twist nonstriated muscle network. Finally, our results suggest a molecular basis for synthetic lethality in which hlh-1 and unc-120 mutant phenotypes are mutually buffered by joint additive regulation of essential target genes, with additional buffering suggested via newly identified hlh-1 interacting factors

Multigenome DNA sequence conservation identifies Hox cis-regulatory elements

To learn how well ungapped sequence comparisons of multiple species can predict cis-regulatory elements in Caenorhabditis elegans, we made such predictions across the large, complex ceh-13/lin-39 locus and tested them transgenically. We also examined how prediction quality varied with different genomes and parameters in our comparisons. Specifically, we sequenced ∼0.5% of the C. brenneri and C. sp. 3 PS1010 genomes, and compared five Caenorhabditis genomes (C. elegans, C. briggsae, C. brenneri, C. remanei, and C. sp. 3 PS1010) to find regulatory elements in 22.8 kb of noncoding sequence from the ceh-13/lin-39 Hox subcluster. We developed the MUSSA program to find ungapped DNA sequences with N-way transitive conservation, applied it to the ceh-13/lin-39 locus, and transgenically assayed 21 regions with both high and low degrees of conservation. This identified 10 functional regulatory elements whose activities matched known ceh-13/lin-39 expression, with 100% specificity and a 77% recovery rate. One element was so well conserved that a similar mouse Hox cluster sequence recapitulated the native nematode expression pattern when tested in worms. Our findings suggest that ungapped sequence comparisons can predict regulatory elements genome-wide

Ror receptor tyrosine kinases: orphans no more

Receptor tyrosine kinase-like orphan receptor (Ror) proteins are a conserved family of tyrosine kinase receptors that function in developmental processes including skeletal and neuronal development, cell movement and cell polarity. Although Ror proteins were originally named because the associated ligand and signaling pathway were unknown, recent studies in multiple species have now established that Ror proteins are Wnt receptors. Depending on the cellular context, Ror proteins can either activate or repress transcription of Wnt target genes and can modulate Wnt signaling by sequestering Wnt ligands. New evidence implicates Ror proteins in planar cell polarity, an alternative Wnt pathway. Here, we review the progress made in understanding these mysterious proteins and, in particular, we focus on their function as Wnt receptors

Invited Article: First Flight in Space of a Wide-Field-of-View Soft X-Ray Imager Using Lobster-Eye Optics: Instrument Description and Initial Flight Results

We describe the development, launch into space, and initial results from a prototype wide eld-of-view (FOV) soft X-ray imager that employs Lobster-eye optics and targets heliophysics, planetary, and astrophysics science. The Sheath Transport Observer for the Redistribution of Mass (STORM) is the rst instrument using this type of optics launched into space and provides proof-of-concept for future ight instruments capable of imaging structures such as the terrestrial cusp, the entire dayside magnetosheath from outside the magnetosphere, comets, the moon, and the solar wind interaction with planetary bodies like Venus and Mars

The Sheath Transport Observer for the Redistribution of Mass (STORM) Imager

All of the solar wind energy that powers magnetospheric processes passes through the magnetosheath and magnetopause. Global images of the magnetosheath and magnetopause boundary layers will resolve longstanding controversies surrounding fundamental phenomena that occur at the magnetopause and provide information needed to improve operational space weather models. Recent developments showing that soft X-rays (0.15-1 keV) result from high charge state solar wind ions undergoing charge exchange recombination through collisions with exospheric neutral atoms has led to the realization that soft X-ray imaging can provide global maps of the high-density shocked solar wind within the magnetosheath and cusps, regions lying between the lower density solar wind and magnetosphere. We discuss an instrument concept called the Sheath Transport Observer for the Redistribution of Mass (STORM), an X-ray imager suitable for simultaneously imaging the dayside magnetosheath, the magnetopause boundary layers, and the cusps

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Developmental landmarks used in study.

<p>Many images of each stage (examples on the left) were averaged to generate composite images (lateral view on the right) for each of the developmental stages, of which 29 are shown.</p

Developmental time of <i>D. melanogaster</i> varies with temperature.

<p>(A) Images of developing <i>D. melanogaster</i> embryos at each temperature are shown for a selection of stages to highlight the overall similarity of development. (B) The time individual animals reached the various time-points are shown, with each event being a different color. Time 0 is defined as the end of cellularization, when the membrane invagination reaches the yolk. Between 17.5°C and 27.5°C the total time of embryogenesis, measured as the mean time between cellularization and trachea fill, has a logarithmic relationship to temperature described by where T is temperature in °C (). (C) The developmental rate in <i>D. melanogaster</i> changes uniformly with temperature, not preferentially affecting any stage. Timing here is normalized between the end of cellularization and the filling of the trachea.</p

Temperature dependent developmental rates are climate specific.

<p>The time between the end of cellularization and trachea fill are shown for all species at a range of temperatures. The climatic groups – tropical (warm colors), alpine (blues), temperate (purple), and sub-tropical (green) – clearly stand out from one another to form four general trends.</p