Recurrent Modification of a Conserved Cis-Regulatory Element Underlies Fruit Fly Pigmentation Diversity

The development of morphological traits occurs through the collective action of networks of genes connected at the level of gene expression. As any node in a network may be a target of evolutionary change, the recurrent targeting of the same node would indicate that the path of evolution is biased for the relevant trait and network. Although examples of parallel evolution have implicated recurrent modification of the same gene and cis-regulatory element (CRE), little is known about the mutational and molecular paths of parallel CRE evolution. In Drosophila melanogaster fruit flies, the Bric-à-brac (Bab) transcription factors control the development of a suite of sexually dimorphic traits on the posterior abdomen. Female-specific Bab expression is regulated by the dimorphic element, a CRE that possesses direct inputs from body plan (ABD-B) and sex-determination (DSX) transcription factors. Here, we find that the recurrent evolutionary modification of this CRE underlies both intraspecific and interspecific variation in female pigmentation in the melanogaster species group. By reconstructing the sequence and regulatory activity of the ancestral Drosophila melanogaster dimorphic element, we demonstrate that a handful of mutations were sufficient to create independent CRE alleles with differing activities. Moreover, intraspecific and interspecific dimorphic element evolution proceeded with little to no alterations to the known body plan and sex-determination regulatory linkages. Collectively, our findings represent an example where the paths of evolution appear biased to a specific CRE, and drastic changes in function were accompanied by deep conservation of key regulatory linkages. © 2013 Rogers et al

Ultra High Energy Cosmology with POLARBEAR

Observations of the temperature anisotropy of the Cosmic Microwave Background (CMB) lend support to an inflationary origin of the universe, yet no direct evidence verifying inflation exists. Many current experiments are focussing on the CMB's polarization anisotropy, specifically its curl component (called "B-mode" polarization), which remains undetected. The inflationary paradigm predicts the existence of a primordial gravitational wave background that imprints a unique B-mode signature on the CMB's polarization at large angular scales. The CMB B-mode signal also encodes gravitational lensing information at smaller angular scales, bearing the imprint of cosmological large scale structures (LSS) which in turn may elucidate the properties of cosmological neutrinos. The quest for detection of these signals; each of which is orders of magnitude smaller than the CMB temperature anisotropy signal, has motivated the development of background-limited detectors with precise control of systematic effects. The POLARBEAR experiment is designed to perform a deep search for the signature of gravitational waves from inflation and to characterize lensing of the CMB by LSS. POLARBEAR is a 3.5 meter ground-based telescope with 3.8 arcminute angular resolution at 150 GHz. At the heart of the POLARBEAR receiver is an array featuring 1274 antenna-coupled superconducting transition edge sensor (TES) bolometers cooled to 0.25 Kelvin. POLARBEAR is designed to reach a tensor-to-scalar ratio of 0.025 after two years of observation -- more than an order of magnitude improvement over the current best results, which would test physics at energies near the GUT scale. POLARBEAR had an engineering run in the Inyo Mountains of Eastern California in 2010 and will begin observations in the Atacama Desert in Chile in 2011.Comment: 8 pages, 6 figures, DPF 2011 conference proceeding

Development and characterization of the readout system for POLARBEAR-2

POLARBEAR-2 is a next-generation receiver for precision measurements of the polarization of the cosmic microwave background (Cosmic Microwave Background (CMB)). Scheduled to deploy in early 2015, it will observe alongside the existing POLARBEAR-1 receiver, on a new telescope in the Simons Array on Cerro Toco in the Atacama desert of Chile. For increased sensitivity, it will feature a larger area focal plane, with a total of 7,588 polarization sensitive antenna-coupled Transition Edge Sensor (TES) bolometers, with a design sensitivity of 4.1 uKrt(s). The focal plane will be cooled to 250 milliKelvin, and the bolometers will be read-out with 40x frequency domain multiplexing, with 36 optical bolometers on a single SQUID amplifier, along with 2 dark bolometers and 2 calibration resistors. To increase the multiplexing factor from 8x for POLARBEAR-1 to 40x for POLARBEAR-2 requires additional bandwidth for SQUID readout and well-defined frequency channel spacing. Extending to these higher frequencies requires new components and design for the LC filters which define channel spacing. The LC filters are cold resonant circuits with an inductor and capacitor in series with each bolometer, and stray inductance in the wiring and equivalent series resistance from the capacitors can affect bolometer operation. We present results from characterizing these new readout components. Integration of the readout system is being done first on a small scale, to ensure that the readout system does not affect bolometer sensitivity or stability, and to validate the overall system before expansion into the full receiver. We present the status of readout integration, and the initial results and status of components for the full array.Comment: Presented at SPIE Astronomical Telescopes and Instrumentation 2014: Millimeter, Submillimeter, and Far-Infrared Detectors and Instrumentation for Astronomy VII. Published in Proceedings of SPIE Volume 915

Comparative effect of ALA derivatives on protoporphyrin IX production in human and rat skin organ cultures

Samples of human and rat skin in short-term organ culture exposed to ALA or a range of hydrophobic derivatives were examined for their effect on the accumulation of protoporphyrin IX (PpIX) measured using fluorescence spectroscopy. With the exception of carbobenzoyloxy-D-phenylalanyl-5-ALA-ethyl ester the data presented indicate that, in normal tissues, ALA derivatives generate protoporphyrin IX more slowly than ALA, suggesting that they are less rapidly taken up and/or converted to free ALA. However, the resultant depot effect may lead to the enhanced accumulation of porphyrin over long exposure periods, particularly in the case of ALA-methyl ester or ALA-hexyl ester, depending on the applied concentration and the exposed tissue. Addition of the iron chelator, CP94, greatly increased PpIX accumulation in human skin exposed to ALA, ALA-methyl ester and ALA-hexyl ester. The effect in rat skin was less marked.</p

Genomic characterization of a repetitive motif strongly associated with developmental genes in Drosophila

BACKGROUND: Non-coding DNA represents a high proportion of all metazoan genomes. Although an undetermined fraction of this DNA may be considered devoid of any function, it also contains important information residing in specific cis-regulatory sequences. RESULTS: We report a 27 bp motif that is overrepresented within the fly genome. This motif does not show any significant similarity with transposon sequences and is strongly associated with genes involved in development and/or signal transduction. The 27 bp motif is preferentially located within introns, and has a tendency to be present in multiple copies around genes. Furthermore, it is often found embedded in known non-coding regulatory regions. The regulatory network defined by this motif is partially shared in D. pseudoobscura. CONCLUSION: We have identified a 27 bp cis-regulatory sequence widely distributed within the Drosophila genome in association with developmental genes. This motif may be very useful towards the annotation of functional regulatory regions within the Drosophila genome and the construction of regulatory networks of Drosophila development

De Novo Genesis of Enhancers in Vertebrates

Whole genome duplication in teleost fish reveals that a few changes in non-regulatory genomic sequences are a source for generating new enhancers

The POLARBEAR-2 and Simons Array Focal Plane Fabrication Status

We present on the status of POLARBEAR-2 A (PB2-A) focal plane fabrication. The PB2-A is the first of three telescopes in the Simon Array (SA), which is an array of three cosmic microwave background (CMB) polarization sensitive telescopes located at the POLARBEAR (PB) site in Northern Chile. As the successor to the PB experiment, each telescope and receiver combination is named as PB2-A, PB2-B, and PB2-C. PB2-A and -B will have nearly identical receivers operating at 90 and 150 GHz while PB2-C will house a receiver operating at 220 and 270 GHz. Each receiver contains a focal plane consisting of seven close-hex packed lenslet coupled sinuous antenna transition edge sensor bolometer arrays. Each array contains 271 di-chroic optical pixels each of which have four TES bolometers for a total of 7588 detectors per receiver. We have produced a set of two types of candidate arrays for PB2-A. The first we call Version 11 (V11) and uses a silicon oxide (SiOx) for the transmission lines and cross-over process for orthogonal polarizations. The second we call Version 13 (V13) and uses silicon nitride (SiNx) for the transmission lines and cross-under process for orthogonal polarizations. We have produced enough of each type of array to fully populate the focal plane of the PB2-A receiver. The average wirebond yield for V11 and V13 arrays is 93.2% and 95.6% respectively. The V11 arrays had a superconducting transition temperature (Tc) of 452 +/- 15 mK, a normal resistance (Rn) of 1.25 +/- 0.20 Ohms, and saturations powers of 5.2 +/- 1.0 pW and 13 +/- 1.2 pW for the 90 and 150 GHz bands respectively. The V13 arrays had a superconducting transition temperature (Tc) of 456 +/-6 mK, a normal resistance (Rn) of 1.1 +/- 0.2 Ohms, and saturations powers of 10.8 +/- 1.8 pW and 22.9 +/- 2.6 pW for the 90 and 150 GHz bands respectively

Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

<p>Abstract</p> <p>Background</p> <p>Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods.</p> <p>Results</p> <p>Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values.</p> <p>Conclusions</p> <p>Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.</p