Crustal and upper-mantle structure in the Eastern Mediterranean from the analysis of surface wave dispersion curves

The dispersive properties of surface waves are used to infer earth structure in the Eastern Mediterranean region. Using group velocity maps for Rayleigh and Love waves from 7100 s, we invert for the best 1D crust and uppermantle structure at a regular series of points. Assembling the results produces a 3D lithospheric model, along with corresponding maps of sediment and crustal thickness. A comparison of our results to other studies finds the uncertainties of the Moho estimates to be about 5 km. We find thick sediments beneath most of the Eastern Mediterranean basin, in the Hellenic subduction zone and the Cyprus arc. The Ionian Sea is more characteristic of oceanic crust than the rest of the Eastern Mediterranean region as demonstrated in particular by the crustal thickness. We also find significant crustal thinning in the Aegean Sea portion of the backarc, particularly towards the south. Notably slower Swave velocities are found in the uppermantle, especially in the northern Red Sea and Dead Sea Rift, central Turkey, and along the subduction zone. The low velocities in the uppermantle that span from North Africa to Crete, in the Libyan Sea, might be an indication of serpentinized mantle from the subducting African lithosphere. We also find evidence of a strong reverse correlation between sediment and crustal thickness which, while previously demonstrated for extensional regions, also seems applicable for this convergence zone

Engineering of a mouse for the in vivo profiling of estrogen receptor activity

In addition to their well known control of reproductive functions, estrogens modulate important physiological processes. The identification of compounds with tissue-selective activity will lead to new drugs mimicking the beneficial effects of estrogen on the prevention of osteoporosis and cardiovascular or neurodegenerative diseases, while avoiding its detrimental proliferative effects. As an innovative model for the in vivo identification of new selective estrogen receptor modulators (SERMs), we engineered a mouse genome to express a luciferase reporter gene ubiquitously. The constructs for transgenesis consist of the reporter gene driven by a dimerized estrogen-responsive element (ERE) and a minimal promoter. Insulator sequences, either matrix attachment region (MAR) or beta -globin hypersensitive site 4 (HS4), flank the construct to achieve a generalized, hormone-responsive luciferase expression. In the mouse we generated, the reporter expression is detectable in all 26 tissues examined, but is induced by 17 beta -estradiol (E-2) only in 15 of them, all expressing estrogen receptors (ERs). Immunohistochemical studies show that in the mouse uterus, luciferase and ERs colocalize. In primary cultures of bone marrow cells explanted from the transgenic mice and in vivo, luciferase activity accumulates with increasing E-2 concentration. E-2 activity is blocked by the ER full antagonist ICI 182,780. Tamoxifen shows partial agonist activity in liver and bone when administered to the animals. In the mouse system here illustrated, by biochemical, immunohistochemical, and pharmacological criteria, luciferase content reflects ER transcriptional activity and thus represents a novel system for the study of ER dynamics during physiological fluctuations of estrogen and for the identification of SERMs or endocrine disrupters

Rayleigh wave dispersion measurements reveal low-velocity zones beneath the new crust in the Gulf of California

Rayleigh wave tomography provides images of the shallow mantle shear wave velocity structure beneath the Gulf of California. Low-velocity zones (LVZs) are found on axis between 26 and 50 km depth beneath the Guaymas Basin but mostly off axis under the other rift basins, with the largest feature underlying the Ballenas Transform Fault. We interpret the broadly distributed LVZs as regions of partial melting in a solid mantle matrix. The pathway for melt migration and focusing is more complex than an axis-centered source aligned above a deeper region of mantle melt and likely reflects the magmatic evolution of rift segments. We also consider the existence of solid lower continental crust in the Gulf north of the Guaymas Basin, where the association of the LVZs with asthenospheric upwelling suggests lateral flow assisted by a heat source. These results provide key constraints for numerical models of mantle upwelling and melt focusing in this young oblique rift

A quality metric for homology modeling: the H-factor

<p>Abstract</p> <p>Background</p> <p>The analysis of protein structures provides fundamental insight into most biochemical functions and consequently into the cause and possible treatment of diseases. As the structures of most known proteins cannot be solved experimentally for technical or sometimes simply for time constraints, <it>in silico </it>protein structure prediction is expected to step in and generate a more complete picture of the protein structure universe. Molecular modeling of protein structures is a fast growing field and tremendous works have been done since the publication of the very first model. The growth of modeling techniques and more specifically of those that rely on the existing experimental knowledge of protein structures is intimately linked to the developments of high resolution, experimental techniques such as NMR, X-ray crystallography and electron microscopy. This strong connection between experimental and <it>in silico </it>methods is however not devoid of criticisms and concerns among modelers as well as among experimentalists.</p> <p>Results</p> <p>In this paper, we focus on homology-modeling and more specifically, we review how it is perceived by the structural biology community and what can be done to impress on the experimentalists that it can be a valuable resource to them. We review the common practices and provide a set of guidelines for building better models. For that purpose, we introduce the H-factor, a new indicator for assessing the quality of homology models, mimicking the R-factor in X-ray crystallography. The methods for computing the H-factor is fully described and validated on a series of test cases.</p> <p>Conclusions</p> <p>We have developed a web service for computing the H-factor for models of a protein structure. This service is freely accessible at <url>http://koehllab.genomecenter.ucdavis.edu/toolkit/h-factor</url>.</p

PRIMO: an interactive homology modeling pipeline

The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling

The FGGY carbohydrate kinase family : insights into the evolution of functional specificities

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS Computational Biology 7 (2011): e1002318, doi:10.1371/journal.pcbi.1002318.Function diversification in large protein families is a major mechanism driving expansion of cellular networks, providing organisms with new metabolic capabilities and thus adding to their evolutionary success. However, our understanding of the evolutionary mechanisms of functional diversity in such families is very limited, which, among many other reasons, is due to the lack of functionally well-characterized sets of proteins. Here, using the FGGY carbohydrate kinase family as an example, we built a confidently annotated reference set (CARS) of proteins by propagating experimentally verified functional assignments to a limited number of homologous proteins that are supported by their genomic and functional contexts. Then, we analyzed, on both the phylogenetic and the molecular levels, the evolution of different functional specificities in this family. The results show that the different functions (substrate specificities) encoded by FGGY kinases have emerged only once in the evolutionary history following an apparently simple divergent evolutionary model. At the same time, on the molecular level, one isofunctional group (L-ribulokinase, AraB) evolved at least two independent solutions that employed distinct specificity-determining residues for the recognition of a same substrate (L-ribulose). Our analysis provides a detailed model of the evolution of the FGGY kinase family. It also shows that only combined molecular and phylogenetic approaches can help reconstruct a full picture of functional diversifications in such diverse families.This study was funded by NIH and DOE grants

Data for: High yield recombinant expression and purification of oncogenic NSD1, NSD2, and NSD3 with human influenza hemagglutinin tag

Recombinant protein expression and affinity column purification of NSD1-CTDS-HA and HA tagging improved the purity and solubility of recombinant NSD constructs

Data for: High yield recombinant expression and purification of oncogenic NSD1, NSD2, and NSD3 with human influenza hemagglutinin tag

Raw processed data used for enzymatic assay