ALBERT

Description: : The protein structure prediction approaches can be categorized into template-based modeling (including homology modeling and threading) and free modeling. However, the existing threading tools perform poorly on remote homologous proteins. Thus, improving fold recognition for remote homologous proteins remains a challenge. Besides, the proteome-wide structure prediction poses another challenge of increasing prediction throughput. In this study, we presented FALCON@home as a protein structure prediction server focusing on remote homologue identification. The design of FALCON@home is based on the observation that a structural template, especially for remote homologous proteins, consists of conserved regions interweaved with highly variable regions. The highly variable regions lead to vague alignments in threading approaches. Thus, FALCON@home first extracts conserved regions from each template and then aligns a query protein with conserved regions only rather than the full-length template directly. This helps avoid the vague alignments rooted in highly variable regions, improving remote homologue identification. We implemented FALCON@home using the Berkeley Open Infrastructure of Network Computing (BOINC) volunteer computing protocol. With computation power donated from over 20 000 volunteer CPUs, FALCON@home shows a throughput as high as processing of over 1000 proteins per day. In the Critical Assessment of protein Structure Prediction (CASP11), the FALCON@home-based prediction was ranked the 12th in the template-based modeling category. As an application, the structures of 880 mouse mitochondria proteins were predicted, which revealed the significant correlation between protein half-lives and protein structural factors. Availability and implementation: FALCON@home is freely available at http://protein.ict.ac.cn/FALCON/ . Contact: shuaicli@cityu.edu.hk , dbu@ict.ac.cn Supplementary information: Supplementary data are available at Bioinformatics online.

Description: With the intensification of the global energy crisis, the production cost of enterprises is continuously increasing because of the rising fuel prices and high requirements for environmental protection. As result, energy savings and environmental protection are vital considerations for a variety of enterprises. As a practical energy-saving technology, oxygen- enriched combustion has played a major role in energy saving and emissions reduction as its application in industrial furnaces has been popularized in recent years. This experiment was conducted in a cement rotary kiln with a capacity of 4000 t/d in a factory in China. Based on measured data in the oxygen-enriched combustion experiment, we determined the patterns of variation in the main parameters of the cement rotary kiln under oxygen-enriched production conditions. The results provide important theoretical and practical base for the cement building materials industry in energy saving and emissions reduction.

Description: X-ray crystallography provides excellent structural data on protein–DNA interfaces, but crystallographic complexes typically contain only small fragments of large DNA molecules. We present a new approach that can use longer DNA substrates and reveal new protein–DNA interactions even in extensively studied systems. Our approach combines rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). DXMS identifies solvent-exposed protein surfaces; docking is used to create a 3-dimensional model of the protein–DNA interaction. We investigated the enzyme uracil-DNA glycosylase (UNG), which detects and cleaves uracil from DNA. UNG was incubated with a 30 bp DNA fragment containing a single uracil, giving the complex with the abasic DNA product. Compared with free UNG, the UNG–DNA complex showed increased solvent protection at the UNG active site and at two regions outside the active site: residues 210–220 and 251–264. Computational docking also identified these two DNA-binding surfaces, but neither shows DNA contact in UNG–DNA crystallographic structures. Our results can be explained by separation of the two DNA strands on one side of the active site. These non-sequence-specific DNA-binding surfaces may aid local uracil search, contribute to binding the abasic DNA product and help present the DNA product to APE-1, the next enzyme on the DNA-repair pathway.

Description: Standard tuberculosis (TB) treatment includes an initial regimen containing drugs that are both rapidly bactericidal (isoniazid) and sterilizing (rifampin and pyrazinamide), and ethambutol to help prevent the emergence of drug resistance. Antagonism between isoniazid and pyrazinamide has been demonstrated in a TB treatment mouse model. Because isoniazid’s bactericidal activity is...

Description: 〈span〉〈div〉Abstract〈/div〉The early continental crust is composed predominantly of Archean tonalite-trondhjemite-granodiorite (TTG); however, the tectonic regime and melting conditions for TTG magmas have been debated. In this study, we report field and microscopic evidence for the partial melting of arc-related metagabbro and its products, including TTG-like melt, volumetrically significant plutons evolved from melt, and the associated granulitic residua during continental collision in the North Qaidam Mountains, China. Migmatite shows successive stages of initial intragranular or droplet-like melt along grain boundaries, which grew into a three-dimensional interconnected intergranular network, segregated, and accumulated in pressure shadow areas, and merged to form melt channels and sheets that finally combined to form a TTG-like tonalite pluton. Pressure-temperature (〈span〉P〈/span〉-〈span〉T〈/span〉) calculations indicate high-pressure granulite-facies metamorphism and the crystallization of leucosome at 〈span〉P〈/span〉 = 15.5–18.5 kbar and 〈span〉T〈/span〉 = 850–950 °C. Based on zircon U-Pb dating and petrological analyses, partial melting and magmatic crystallization occurred 438–430 m.y. ago, which is slightly younger or temporally overlaps with ultrahigh-pressure metamorphism in the region. The metagabbros exhibit a subduction-related arc signature with slightly positive ε〈sub〉Nd〈/sub〉(〈span〉t〈/span〉) values of 2.1–4.2. The felsic leucosomes and tonalite plutons are characterized by high Na, Sr, Sr/Y, and La/Yb values and low heavy rare earth element values, with ε〈sub〉Nd〈/sub〉(〈span〉t〈/span〉) values of 0.1–4.3, similar to typical TTGs. The geological context, geochemistry, and timing of the TTG-like melt formation observed in this study differ from the prevailing models; however, our observations and documentations demonstrate that melting of arc-like metagabbro under high-pressure granulite-facies conditions during continental collision may make important contributions to crustal growth and differentiation.〈/span〉

Description: Author(s): N. Vafaei-Najafabadi, K. A. Marsh, C. E. Clayton, W. An, W. B. Mori, C. Joshi, W. Lu, E. Adli, S. Corde, M. Litos, S. Li, S. Gessner, J. Frederico, A. S. Fisher, Z. Wu, D. Walz, R. J. England, J. P. Delahaye, C. I. Clarke, M. J. Hogan, and P. Muggli We show through experiments and supporting simulations that propagation of a highly relativistic and dense electron bunch through a plasma can lead to distributed injection of electrons, which depletes the accelerating field, i.e., beam loads the wake. The source of the injected electrons is ionizat... [Phys. Rev. Lett. 112, 025001] Published Wed Jan 15, 2014

Description: Author(s): W. An, M. Zhou, N. Vafaei-Najafabadi, K. A. Marsh, C. E. Clayton, C. Joshi, W. B. Mori, W. Lu, E. Adli, S. Corde, M. Litos, S. Li, S. Gessner, J. Frederico, M. J. Hogan, D. Walz, J. England, J. P. Delahaye, and P. Muggli Strategies for mitigating ionization-induced beam head erosion in an electron-beam-driven plasma wakefield accelerator (PWFA) are explored when the plasma and the wake are both formed by the transverse electric field of the beam itself. Beam head erosion can occur in a preformed plasma because of a ... [Phys. Rev. ST Accel. Beams 16, 101301] Published Wed Oct 09, 2013

Description: Motivation: Understanding how drugs and diseases are associated in the molecular level is of critical importance to unveil disease mechanisms and treatments. Until recently, few studies attempt end to discover important gene modules shared by both drugs and diseases. Results: Here, we propose a novel presentation of drug–gene–disease relationship, a ‘co-module’, which is characterized by closely related drugs, diseases and genes. We first define a network-based gene closeness profile to relate drug to disease. Then, we develop a Bayesian partition method to identify drug–gene–disease co-modules underlying the gene closeness data. Genes share similar notable patterns with respect not only to the drugs but also the diseases within a co-module. Simulations show that our method, comCIPHER, achieves a better performance compared with a popular co-module detection method, PPA. We apply comCIPHER to a set consisting of 723 drugs, 275 diseases and 1442 genes and demonstrate that our co-module approach is able to identify new drug–disease associations and highlight their molecular basis. Disease co-morbidity emerges as well. Three co-modules are further illustrated in which new drug applications, including the anti-cancer metastasis activity of an anti-asthma drug Pranlukast, and a cardiovascular stress-testing agent Arbutamine for obesity, as well as potential side-effects, e.g. hypotension for Triamterene, are computationally identified. Availability: The compiled version of comCIPHER can be found at http://bioinfo.au.tsinghua.edu.cn/comCIPHER/ . The 86 co-modules can be downloaded from http://bioinfo.au.tsinghua.edu.cn/comCIPHER/Co_Module_Results.zip . Contact: shaoli@mail.tsinghua.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online.

Description: SUMMARY In this paper, we conduct ambient noise seismic tomography of northwestern China and adjacent regions. The data include 9 months (2009 January to 2009 September) three-component continuous data recorded at 146 seismic stations of newly upgraded China Provincial Digital Seismic Networks and regional Kyrgyzstan and Kazakhstan networks. Empirical Rayleigh and Love wave Green's functions are obtained from interstation cross-correlations. Group velocity dispersion curves for both Rayleigh and Love waves between 7 and 50 s periods were measured for each interstation path by applying the multiple-filter analysis method with phase-matched processing. The group velocity maps show clear lateral variations which correlate well with major geological structures and tectonic units in the study region. Shear wave velocity structures are inverted from Rayleigh wave and love wave dispersion maps. The results show that the Tibetan Plateau has a very thick crust with a low-velocity zone in its mid-lower crust. Along the northern margin of the plateau where a steep topographic gradient is present, the low-velocity zone does not extend to the Tarim basin which may indicate that crustal materials beneath the Tarim basin are colder and stronger than beneath the plateau, therefore inhibit the extension of mid-lower crustal flow and deformation of the Tibetan Plateau, resulting in very sharp topography contrasts. In the northeastern margin with a gentle topographic gradient toward the Ordos platform, the low-velocity zone diminishes around the eastern KunLun fault. Meanwhile, our results reveal obvious lateral velocity changes in the crust beneath the Tarim basin. In the upper crust, the Manjaer depression in the eastern Tarim basin is featured with very low velocities and the Bachu uplift in the western Tarim basin with high velocities; in the mid-lower crust, the northern Tarim basin in general displays lower velocities than the southern part along latitude ∼40° N with an east–west striking, which is consistent with the high magnetic anomaly zone and may be related to the central suture belt connecting the south and north of Tarim basement blocks together in Pre-Sinian.

Description: NONO, SFPQ and PSPC1 make up a family of proteins with diverse roles in transcription, RNA processing and DNA double-strand break (DSB) repair. To understand long-term effects of loss of NONO, we characterized murine embryonic fibroblasts (MEFs) from knockout mice. In the absence of genotoxic stress, wild-type and mutant MEFs showed similar growth rates and cell cycle distributions, and the mutants were only mildly radiosensitive. Further investigation showed that NONO deficiency led to upregulation of PSPC1, which replaced NONO in a stable complex with SFPQ. Knockdown of PSPC1 in a NONO-deficient background led to severe radiosensitivity and delayed resolution of DSB repair foci. The DNA-dependent protein kinase (DNA-PK) inhibitor, NU7741, sensitized wild-type and singly deficient MEFs, but had no additional effect on doubly deficient cells, suggesting that NONO/PSPC1 and DNA-PK function in the same pathway. We tested whether NONO and PSPC1 might also affect repair indirectly by influencing mRNA levels for other DSB repair genes. Of 12 genes tested, none were downregulated, and several were upregulated. Thus, NONO or related proteins are critical for DSB repair, NONO and PSPC1 are functional homologs with partially interchangeable functions and a compensatory response involving PSPC1 blunts the effect of NONO deficiency.