Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila

BACKGROUND: The discovery of cis-regulatory modules in metazoan genomes is crucial for understanding the connection between genes and organism diversity. It is important to quantify how comparative genomics can improve computational detection of such modules. RESULTS: We run the Stubb software on the entire D. melanogaster genome, to obtain predictions of modules involved in segmentation of the embryo. Stubb uses a probabilistic model to score sequences for clustering of transcription factor binding sites, and can exploit multiple species data within the same probabilistic framework. The predictions are evaluated using publicly available gene expression data for thousands of genes, after careful manual annotation. We demonstrate that the use of a second genome (D. pseudoobscura) for cross-species comparison significantly improves the prediction accuracy of Stubb, and is a more sensitive approach than intersecting the results of separate runs over the two genomes. The entire list of predictions is made available online. CONCLUSION: Evolutionary conservation of modules serves as a filter to improve their detection in silico. The future availability of additional fruitfly genomes therefore carries the prospect of highly specific genome-wide predictions using Stubb

Do Demographics Prevent Consumption Aggregates From Reflecting Micro-Level Preferences?

Most simulated micro-founded macro models use solely consumer-demand aggregates in order to estimate preference parameters of a representative consumer, for use in policy evaluation. Focusing on dynamic models with time-separable preferences, we show that aggregation holds if, and only if, momentary utility functions fall in the Identical-Shape Harmonic Absolute-Risk Aversion (ISHARA) utility class, identifying which parameters of ISHARA utility functions are allowed to vary over time. Given this theoretical result, it should be easy to empirically reject the aggregation properties that the macroeconomic representative-consumer identification approach requires: it suffices to show that permanent incomes guaranteeing the same living standard across households of different size violate an affine relationship. In order to test the validity of this affine equation, we develop a vignette survey that produces appropriate data without demand-estimation restrictions imposed by models. Surprisingly, in six countries, this equation is not rejected, lending support to using consumer-demand aggregates

Nonvolcanic seafloor spreading and corner-flow rotation accommodated by extensional faulting at 15°N on the Mid-Atlantic Ridge : a structural synthesis of ODP Leg 209

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 8 (2007): Q06015, doi:10.1029/2006GC001567.Drilling during ODP Leg 209, dredging, and submersible dives have delineated an anomalous stretch of the Mid-Atlantic Ridge north and south of the 15°20′N Fracture Zone. The seafloor here consists dominantly of mantle peridotite with gabbroic intrusions that in places is covered by a thin, discontinuous extrusive volcanic layer. Thick lithosphere (10–20 km) in this region inhibits magma from reaching shallow levels beneath the ridge axis, thereby causing plate accretion to be accommodated by extensional faulting rather than magmatism. The bathymetry and complex fault relations in the drill-core suggest that mantle denudation and spreading are accommodated by a combination of high-displacement, rolling-hinge normal faults and secondary lower-displacement normal faults. These extensional faults must also accommodate corner flow rotation (up to 90°) of the upwelling mantle within the shallow lithosphere, consistent with remnant magnetic inclinations in denuded peridotite and gabbro from Leg 209 core that indicate up to 90° of sub-Curie-temperature rotation.This work was funded by a grant from the Joint Oceanographic Institutions

A celestial matryoshka: Dynamical and spectroscopic analysis of the Albireo system

We present a spectroscopic characterisation and a new orbital solution for the binary system beta Cyg Aa/Ac (MCA 55), the primary component (beta Cyg A) of the well-known wide double star Albireo. By matching evolutionary tracks to the physical parameters of all three Albireo stars (beta Cyg Aa, Ac and B) as obtained from a spectroscopic analysis of TIGRE and IUE spectra, we confirm that they are likely coeval. Our final orbit solution is based on radial-velocity measurements taken over a baseline exceeding $120$ years, combined with relative astrometry from speckle interferometric observations and the absolute astrometry from the Hipparcos and Gaia missions. Our final orbit solution has a period of $121.65^{+3.34}_{-2.90}$ years with an eccentricity of $0.20^{+0.01}_{-0.02}$. Thanks to the inclusion of the absolute astrometry, we find a mass ratio of $q = 1.25^{+0.19}_{-0.17}$, and a total mass of $9.47_{-3.24}^{+5.88}$ M$_\odot$, indicating that the secondary (Ac) is the more massive of the pair. These results strongly suggest the presence of a fourth, unseen, member of the Albireo system. Given the current photometric data it is likely that beta Cyg A is itself a hierarchical triple. We also derive the systemic proper motion, line-of-sight velocity, and an orbital parallax of the beta Cyg A system, allowing us to quantitatively assess the hypothesis that Albireo A and B form a physically bound and genealogically connected system. Finally, we find four potential members of a common proper motion group with Albireo, though none anywhere as close by as the Albireo components A to B.Comment: final draft of accepted manuscrip

Prognostic impact of pretransplant measurable residual disease assessed by peripheral blood WT1-mRNA expression in patients with AML and MDS

OBJECTIVE As peripheral blood (PB) Wilm's Tumor 1 (WT1)-mRNA expression is established as MRD-marker during conventional AML chemotherapy, impact of pretransplant WT1 expression remains unclear. Therefore, we aimed to assess prognostic impact of pretransplant WT1 expression on post-transplant outcome in patients with AML/MDS. METHODS In 64 AML/MDS patients, pretransplant WT1 expression was retrospectively analyzed using a standardized assay offering high sensitivity, specificity, and a validated cut-off. Patients were divided into three groups determined by pretransplant remission and WT1 expression. Post-transplant outcome of these groups was compared regarding cumulative incidence of relapse (CIR), relapse-free (RFS), and overall survival (OS). RESULTS Pretransplant forty-six patients (72%) showed hematologic remission, including 21 (46%) MRD-negative and 25 (54%) MRD-positive patients indicated by WT1 expression, while 18 refractory patients (28%) showed active disease. Two-year estimates of post-transplant CIR, RFS, and OS were similar in MRD-positive (61%, 37%, 54%) and refractory patients (70%, 26%, 56%), but significantly inferior compared with MRD-negative patients (10%, 89%, 90%). After multivariable adjustment, pretransplant MRD negativity measured by WT1 expression retained its prognostic impact on CIR (P~=~.008), RFS (P~=~.005), and OS (P~=~.049). CONCLUSIONS PB WT1 expression represents a useful method to estimate pretransplant MRD, which is highly predictable for post-transplant outcome and may help improving peri-transplant management in AML/MDS patients