| 1. |
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| 2. |
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| 3. |
- Ablikim, M., et al.
(author)
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Measurement of the leptonic decay width of J/psi using initial state radiation
- 2016
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In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 761, s. 98-103
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Journal article (peer-reviewed)abstract
- Using a data set of 2.93 fb(-1) taken at a center-of-mass energy of root s = 3.773 GeV with the BESIII detector at the BEPCII collider, we measure the process e(+) e(-) -> J/psi gamma -> mu(+)mu(-)gamma and determine the product of the branching fraction and the electronic width B-mu mu . Gamma(ee) = (333.4 +/- 2.5(stat) +/- 4.4(sys)) eV. Using the earlier-published BESIII result for B-mu mu = (5.973 +/- 0.007(stat) +/- 0.037(sys))%, we derive the J/psi electronic width Gamma(ee) = (5.58 +/- 0.05(stat) +/- 0.08(sys)) keV. (C) 2016 The Author(s). Published by Elsevier B.V.
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| 4. |
- Hyde, K. D., et al.
(author)
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Global consortium for the classification of fungi and fungus-like taxa
- 2023
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In: MYCOSPHERE. - : Mushroom Research Foundation. - 2077-7000 .- 2077-7019. ; 14:1, s. 1960-2012
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Journal article (peer-reviewed)abstract
- The Global Consortium for the Classification of Fungi and fungus-like taxa is an international initiative of more than 550 mycologists to develop an electronic structure for the classification of these organisms. The members of the Consortium originate from 55 countries/regions worldwide, from a wide range of disciplines, and include senior, mid-career and early-career mycologists and plant pathologists. The Consortium will publish a biannual update of the Outline of Fungi and fungus-like taxa, to act as an international scheme for other scientists. Notes on all newly published taxa at or above the level of species will be prepared and published online on the Outline of Fungi website (https://www.outlineoffungi.org/), and these will be finally published in the biannual edition of the Outline of Fungi and fungus-like taxa. Comments on recent important taxonomic opinions on controversial topics will be included in the biannual outline. For example, 'to promote a more stable taxonomy in Fusarium given the divergences over its generic delimitation', or 'are there too many genera in the Boletales?' and even more importantly, 'what should be done with the tremendously diverse 'dark fungal taxa?' There are undeniable differences in mycologists' perceptions and opinions regarding species classification as well as the establishment of new species. Given the pluralistic nature of fungal taxonomy and its implications for species concepts and the nature of species, this consortium aims to provide a platform to better refine and stabilise fungal classification, taking into consideration views from different parties. In the future, a confidential voting system will be set up to gauge the opinions of all mycologists in the Consortium on important topics. The results of such surveys will be presented to the International Commission on the Taxonomy of Fungi (ICTF) and the Nomenclature Committee for Fungi (NCF) with opinions and percentages of votes for and against. Criticisms based on scientific evidence with regards to nomenclature, classifications, and taxonomic concepts will be welcomed, and any recommendations on specific taxonomic issues will also be encouraged; however, we will encourage professionally and ethically responsible criticisms of others' work. This biannual ongoing project will provide an outlet for advances in various topics of fungal classification, nomenclature, and taxonomic concepts and lead to a community-agreed classification scheme for the fungi and fungus-like taxa. Interested parties should contact the lead author if they would like to be involved in future outlines.
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| 5. |
- Su, Xiao-Dong, et al.
(author)
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Protein crystallography from the perspective of technology developments
- 2015
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In: Crystallography Reviews. - 0889-311X. ; 21:1-2, s. 122-153
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Research review (peer-reviewed)abstract
- Early on, crystallography was a domain of mineralogy and mathematics and dealt mostly with symmetry properties and imaginary crystal lattices. This changed when Wilhelm Conrad Rontgen discovered X-rays in 1895, and in 1912, Max von Laue and his associates discovered that X-ray irradiated salt crystals would produce diffraction patterns that could reveal the internal atomic periodicity of the crystals. In the same year, the father-and-son team, Henry and Lawrence Bragg successfully solved the first crystal structure of sodium chloride and the era of modern crystallography began. Protein crystallography (PX) started some 20 years later with the pioneering work of British crystallographers. In the past 50-60 years, the achievements of modern crystallography and particularly those in PX have been due to breakthroughs in theoretical and technical advancements such as phasing and direct methods; to more powerful X-ray sources such as synchrotron radiation; to more sensitive and efficient X-ray detectors; to ever faster computers and to improvements in software. The exponential development of PX has been accelerated by the invention and applications of recombinant DNA technology that can yield nearly any protein of interest in large amounts and with relative ease. Novel methods, informatics platforms and technologies for automation and high-throughput have allowed the development of large-scale, high-efficiency macromolecular crystallography efforts in the field of structural genomics. Very recently, the X-ray free-electron laser sources and its applications in PX have shown great potential for revolutionizing the whole field again in the near future.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
- Su, Xiao Dong, et al.
(author)
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A large-scale, high-efficiency and low-cost platform for structural genomics studies
- 2006
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In: Acta Crystallographica. Section D: Biological Crystallography. - 0907-4449. ; 62:Pt 8, s. 51-843
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Journal article (peer-reviewed)abstract
- A large-scale, high-efficiency and low-cost platform based on a Beckman Coulter Biomek FX and custom-made automation systems for structural genomics has been set up at Peking University, Beijing, People's Republic of China. This platform has the capacity to process up to 2000 genes per year for structural and functional analyses. Bacillus subtilis, a model organism for Gram-positive bacteria, and Streptococcus mutans, a major pathogen of dental caries, were selected as the main targets. To date, more than 470 B. subtilis and 1200 S. mutans proteins and hundreds of proteins from other sources, including human liver proteins, have been selected as targets for this platform. The selected genes are mainly related to important metabolism pathways and/or have potential relevance for drug design. To date, 40 independent structures have been determined; of these 11 are in the category of novel structures by the criterion of having less than 30% sequence identity to known structures. More than 13 structures were determined by SAD/MAD phasing. The macromolecular crystallography beamline at the Beijing Synchrotron Radiation Facility and modern phasing programs have been crucial components of the operation of the platform. The idea and practice of the genomic approach have been successfully adopted in a moderately funded structural biology program and it is believed this adaptation will greatly improve the production of protein structures. The goal is to be able to solve a protein structure of moderate difficulty at a cost about US 10,000 dollars.
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| 10. |
- Tang, Jinfeng, 1984, et al.
(author)
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Optimizing critical metals recovery and correlative decontamination from MSWI fly ash: Evaluation of an integrating two-step leaching hydrometallurgical process
- 2022
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In: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526. ; 368
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Journal article (peer-reviewed)abstract
- While municipal solid waste incineration (MSWI) fly ash is classified as hazardous waste, it can also serve as an urban mining source for numerous precious metals. Of particular interest are antimony (Sb) and zinc (Zn); the former of which is a strategic and critical metal that is being rapidly depleted, putting society at high risk for supply shortages. In this work, a two-step leaching method for recovering Sb and Zn from MSWI fly ash is proposed. Furthermore, the leaching behavior and adsorption mechanism of Sb in the MSWI fly ash waste stream were also investigated. Results from the first constant pH leaching tests (CPLT) showed that under diluted acidic condition, the maximum amount of Sb released from fly ash was ∼20%. In addition, at pH 4.0, 67% of the fly ash was dissolved, while 79.3% and 12.1% of the Zn and Sb, respectively, were recovered. After optimizing and executing a second Sb leaching procedure (6 M HCl solution at 60 °C), >80% of the Sb was recovered. Thus, the proposed two-step leaching process, consisting of extraction followed by decontamination using a magnetic HAP@CoFe2O4 adsorbent, can eliminate the Sb in fly ash effluent with a removal efficiency >95%. Moreover, this process produces less toxic products and lowers the effluent residue concentration. As such, the two-step process described herein is suggested for Sb and Zn recovery from fly ash; as it not only enables precious metal recovery, but also aids in treating secondary waste streams produced from urban mining.
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| 11. |
- Tang, Ting-Ting, et al.
(author)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Journal article (peer-reviewed)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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| 12. |
- Wang, Kai-Tuo, et al.
(author)
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Structure of the bifunctional methyltransferase YcbY (RlmKL) that adds the m7G2069 and m2G2445 modifications in Escherichia coli 23S rRNA
- 2012
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 40:11, s. 48-5138
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Journal article (peer-reviewed)abstract
- The 23S rRNA nucleotide m(2)G2445 is highly conserved in bacteria, and in Escherichia coli this modification is added by the enzyme YcbY. With lengths of around 700 amino acids, YcbY orthologs are the largest rRNA methyltransferases identified in Gram-negative bacteria, and they appear to be fusions from two separate proteins found in Gram-positives. The crystal structures described here show that both the N- and C-terminal halves of E. coli YcbY have a methyltransferase active site and their folding patterns respectively resemble the Streptococcus mutans proteins Smu472 and Smu776. Mass spectrometric analyses of 23S rRNAs showed that the N-terminal region of YcbY and Smu472 are functionally equivalent and add the m(2)G2445 modification, while the C-terminal region of YcbY is responsible for the m(7)G2069 methylation on the opposite side of the same helix (H74). Smu776 does not target G2069, and this nucleotide remains unmodified in Gram-positive rRNAs. The E.coli YcbY enzyme is the first example of a methyltransferase catalyzing two mechanistically different types of RNA modification, and has been renamed as the Ribosomal large subunit methyltransferase, RlmKL. Our structural and functional data provide insights into how this bifunctional enzyme evolved.
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| 13. |
- Alvarez Fernandez, Marcia, et al.
(author)
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Crystal structure of human cystatin D, a cysteine peptidase inhibitor with restricted inhibition profile.
- 2005
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In: Journal of Biological Chemistry. - 1083-351X. ; 280:18, s. 18221-18228
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Journal article (peer-reviewed)abstract
- Cystatins are natural inhibitors of papain-like (family C1) and legumain-related (family C13) cysteine peptidases. Cystatin D is a type 2 cystatin, a secreted inhibitor found in human saliva and tear fluid. Compared to its homologues, cystatin D presents an unusual inhibition profile with a preferential inhibition cathepsin S > cathepsin H > cathepsin L, and no inhibition of cathepsin B or pig legumain. To elucidate the structural reasons for this specificity, we have crystallized recombinant human Arg26-cystatin D and solved its structures at room temperature and at cryo conditions to 2.5 and 1.8 Å resolution, respectively. Human cystatin D presents the typical cystatin fold, with a five-stranded anti-parallel -sheet wrapped around a five-turn -helix. The structures reveal differences in the peptidase-interacting regions when compared to other cystatins, providing plausible explanations to the restricted inhibitory specificity of cystatin D for some papain-like peptidases, and its lack of reactivity towards legumain-related enzymes. This is the final, accepted and revised manuscript of this article. Use alternative location to go to the published article. Requires subscription.
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| 14. |
- Andersson, Martin E, et al.
(author)
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Structural and mutational studies of the carboxylate cluster in iron-free ribonucleotide reductase R2.
- 2004
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In: Biochemistry. - 0006-2960. ; 43:24, s. 7966-72
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Journal article (peer-reviewed)abstract
- The R2 protein of ribonucleotide reductase features a di-iron site deeply buried in the protein interior. The apo form of the R2 protein has an unusual clustering of carboxylate side chains at the empty metal-binding site. In a previous study, it was found that the loss of the four positive charge equivalents of the diferrous site in the apo protein appeared to be compensated for by the protonation of two histidine and two carboxylate side chains. We have studied the consequences of removing and introducing charged residues on the local hydrogen-bonding pattern in the region of the carboxylate cluster of Corynebacterium ammoniagenes and Escherichia coli protein R2 using site-directed mutagenesis and X-ray crystallography. The structures of the metal-free forms of wild-type C. ammoniagenes R2 and the mutant E. coli proteins D84N, S114D, E115A, H118A, and E238A have been determined and their hydrogen bonding and protonation states have been structurally assigned as far as possible. Significant alterations to the hydrogen-bonding patterns, protonation states, and hydration is observed for all mutant E. coli apo proteins as compared to wild-type apo R2. Further structural variations are revealed by the wild-type apo C. ammoniagenes R2 structure. The protonation and hydration effects seen in the carboxylate cluster appear to be due to two major factors: conservation of the overall charge of the site and the requirement of electrostatic shielding of clustered carboxylate residues. Very short hydrogen-bonding distances between some protonated carboxylate pairs are indicative of low-barrier hydrogen bonding.
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| 15. |
- Bakhtiar, Shahrzad, et al.
(author)
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Crystallization and preliminary X-ray analysis of an alkaline serine protease from Nesterenkonia sp. Acta
- 2003
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In: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 59:3, s. 529-531
-
Journal article (peer-reviewed)abstract
- A novel calcium-independent serine protease from an alkaliphilic bacterium, Nesterenkonia sp. AL20, has been purified and crystallized at 296 K using sodium formate as the main precipitant. This enzyme is optimally active at pH 10, exhibits high stability towards autolytic digestion and its stability is not affected by the presence of EDTA or detergents. The triangular prism-shaped crystals diffracted X-rays to beyond 1.5 Å at a synchrotron beamline, with space group R3 and unit-cell parameters a = b = 92.26, c = 137.88 Å. A complete data set has been collected to 1.39 Å resolution. The asymmetric unit is estimated and confirmed by self-rotation function calculation to contain two molecules, giving a crystal volume per protein mass (VM) of 2.68 Å3 Da-1 and a solvent content of 54%.
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| 16. |
- Brostromer, Erik, et al.
(author)
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An automated image-collection system for crystallization experiments using SBS standard microplates
- 2007
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In: Acta Crystallographica. Section D: Biological Crystallography. - 0907-4449. ; 63:Pt 2, s. 25-119
-
Journal article (peer-reviewed)abstract
- As part of a structural genomics platform in a university laboratory, a low-cost in-house-developed automated imaging system for SBS microplate experiments has been designed and constructed. The imaging system can scan a microplate in 2-6 min for a 96-well plate depending on the plate layout and scanning options. A web-based crystallization database system has been developed, enabling users to follow their crystallization experiments from a web browser. As the system has been designed and built by students and crystallographers using commercially available parts, this report is aimed to serve as a do-it-yourself example for laboratory robotics.
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| 17. |
- Brostromer, Erik, et al.
(author)
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Solid-liquid interface method (SLIM) : a new crystallization method for proteins
- 2009
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 386:4, s. 8-634
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Journal article (peer-reviewed)abstract
- Despite impressive advances in theories, methods and technologies, crystallization still remains a serious bottleneck in structural determination of macromolecules. Here we present a novel solid-liquid interface method (SLIM) for protein crystallization, based on the pre-adding and drying of a crystallization reagent, and thereafter the dispensing of a protein solution to the dried media to initiate crystallization from the solid-liquid interface. Not only quick and easy to perform, the method also allows for a less concentrated protein solution for setting up crystallization trials.
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| 18. |
- Chen, Zhishan, et al.
(author)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 19. |
- Ding, HT, et al.
(author)
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Parallel cloning, expression, purification and crystallization of human proteins for structural genomics
- 2002
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In: Acta Crystallographica. Section D: Biological Crystallography. - 1399-0047. ; 58, s. 2102-2108
-
Journal article (peer-reviewed)abstract
- 54 human genes were selected as test targets for parallel cloning, expression, purification and crystallization. Proteins from these genes were selected to have a molecular weight of between 14 and 50 kDa, not to have a high percentage of hydrophobic residues (i.e. more likely to be soluble) and to have no known crystal structures and were not known to be subunits of heterocomplexes. Four proteins containing transmembrane regions were selected for comparative tests. To date, 44 expression clones have been constructed with the Gateway(TM) cloning system (Invitrogen, The Netherlands). Of these, 35 clones were expressed as recombinant proteins in Escherichia coli strain BL21 (DE3)-pLysS, of which 12 were soluble and four have been purified to homogeneity. Crystallization conditions were screened for the purified proteins in 96-well plates under oil. After further refinement with the same device or by the hanging-drop method, crystals were grown, with needle, plate and prism shapes. A 2.12 Angstrom data set was collected for protein NCC27. The results provide insights into the high-throughput target selection, cloning, expression and crystallization of human genomic proteins.
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| 20. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Journal article (peer-reviewed)abstract
- Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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| 21. |
- Duan, Ming-Rui, et al.
(author)
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DNA binding mechanism revealed by high resolution crystal structure of Arabidopsis thaliana WRKY1 protein
- 2007
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 35:4, s. 54-1145
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Journal article (peer-reviewed)abstract
- WRKY proteins, defined by the conserved WRKYGQK sequence, are comprised of a large superfamily of transcription factors identified specifically from the plant kingdom. This superfamily plays important roles in plant disease resistance, abiotic stress, senescence as well as in some developmental processes. In this study, the Arabidopsis WRKY1 was shown to be involved in the salicylic acid signaling pathway and partially dependent on NPR1; a C-terminal domain of WRKY1, AtWRKY1-C, was constructed for structural studies. Previous investigations showed that DNA binding of the WRKY proteins was localized at the WRKY domains and these domains may define novel zinc-binding motifs. The crystal structure of the AtWRKY1-C determined at 1.6 A resolution has revealed that this domain is composed of a globular structure with five beta strands, forming an antiparallel beta-sheet. A novel zinc-binding site is situated at one end of the beta-sheet, between strands beta4 and beta5. Based on this high-resolution crystal structure and site-directed mutagenesis, we have defined and confirmed that the DNA-binding residues of AtWRKY1-C are located at beta2 and beta3 strands. These results provided us with structural information to understand the mechanism of transcriptional control and signal transduction events of the WRKY proteins.
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| 22. |
- Fenstermacher, M.E., et al.
(author)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Journal article (peer-reviewed)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 23. |
- Fernandez-Rozadilla, Ceres, et al.
(author)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
-
In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
-
Journal article (peer-reviewed)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 24. |
- Fu, Tian-Min, et al.
(author)
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Protein preparation, crystallization and preliminary X-ray analysis of the C-terminal domain of human RSK1 serine/threonine protein kinase
- 2007
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In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications. - 2053-230X. ; 63:Pt 12, s. 8-1026
-
Journal article (peer-reviewed)abstract
- As a substrate of extracellular signal-related kinase (ERK), the p90 ribosome S6 kinase 1 (RSK1) is at the terminus of the Ras/ERK pathway. Residues 411-735 of human RSK1, covering the C-terminal serine/threonine kinase catalytic domain and the functionally important tail, were cloned into an Escherichia coli expression vector. The protein was expressed, purified and crystallized. The crystals diffracted to 2.7 A and belonged to space group P2(1), with unit-cell parameters a = 39.8, b = 143.8, c = 59.9 A, beta = 95.7 degrees.
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| 25. |
- Gao, Rong, et al.
(author)
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Deep sequencing reveals global patterns of mRNA recruitment during translation initiation
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- In this work, we developed a method to systematically study the sequence preference of mRNAs during translation initiation. Traditionally, the dynamic process of translation initiation has been studied at the single molecule level with limited sequencing possibility. Using deep sequencing techniques, we identified the sequence preference at different stages of the initiation complexes. Our results provide a comprehensive and dynamic view of the initiation elements in the translation initiation region (TIR), including the S1 binding sequence, the Shine-Dalgarno (SD)/anti-SD interaction and the second codon, at the equilibrium of different initiation complexes. Moreover, our experiments reveal the conformational changes and regional dynamics throughout the dynamic process of mRNA recruitment.
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