| 1. |
- Birney, Ewan, et al.
(author)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Tian, Yu-peng, et al.
(author)
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Synthesis, crystal structure and NLO properties of a novel ruthenium(II) complex with unusual coordination mode
- 2005
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In: Transition metal chemistry (Weinheim). - : Kluwer Academic Publishers. - 0340-4285 .- 1572-901X. ; 30:7, s. 778-785
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Journal article (peer-reviewed)abstract
- A new Schiff base 4-[N-hydroxyethyl-N-(methyl)amino]benzaldehyde S-methyl dithiocarbazate (HL, where H is a dissociable proton) and the ruthenium complex [Ru(bpy)2L]PF6 (bpy = 2,2′-bipyridine) have been synthesized. The structural determinations of the ligand and its ruthenium complex, by X-ray crystallography, show that the ligand is coordinated as a monoanionic bidentate N, S-donor, forming a four-member chelate ring with a bite angle of 65.91°. The complex shows intense MLCT transitions in the visible region. Fluorescent and electrochemical properties have been also studied. The complex in DMF solution exhibited a strong two-photon absorption (t.p.a.) at 532 nm nanosecond laser pulses. The t.p.a. coefficient β, t.p.a. cross-section σ and the third-order optical nonlinearity χ(3) of the complex and the ligand have been determined by the Z-scan technique.
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| 3. |
- Luo, Jun, et al.
(author)
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Effects of Carbon on Schottky Barrier Heights of NiSi Modified by Dopant Segregation
- 2009
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In: IEEE Electron Device Letters. - : Institute of Electrical and Electronics Engineers (IEEE). - 0741-3106 .- 1558-0563. ; 30:6, s. 608-610
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Journal article (peer-reviewed)abstract
- The presence of carbon at the interface between NiSi and Si has been found to participate in the process of modification of effective Schottky barrier heights using the dopant segregation (DS) method. Carbon alone results in an increased phi(bn) from 0.7 to above 0.9 eV. Boron diffusion in NiSi is inhibited by carbon, and no B-DS at the NiSi/Si interface occurs below 600 degrees C. Above this temperature, B-DS at this interface is evident thus keeping phi(bn) high. The presence of interfacial carbon leads to an increased interfacial As concentration resulting in beneficial effects in tuning phi(bn) above 1.0 eV by As-DS.
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| 4. |
- Zhang, Xiaoying, et al.
(author)
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IL-6 Regulates MMP-10 Expression via JAK2/STAT3 Signaling Pathway in a Human Lung Adenocarcinoma Cell Line
- 2009
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In: Anticancer research. - 1791-7530. ; 29:11, s. 4497-4501
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Journal article (peer-reviewed)abstract
- We previously reported that matrix metalloproteinase (MMP)-10 mRNA levels were significantly lower in tumor tissues than in adjacent normal tissues in human non-small cell lung cancer (NSCLC), whereas protein levels of MMP-10 were higher in the tumor tissues than the adjacent tissues. The mechanism of this divergence is still unknown. In the present stud), the role of Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3) on interleukin (IL)-6 mediated regulation of MMP-10 expression was investigated in a human lung adenocarcinoma cell line (A549 cells) and the molecular regulatory mechanism of MMP-10 expression was explored. A549 cells were stimulated by different concentrations of IL-6 with or without AG490, a specific JAK2 inhibitor. It was demonstrated that IL-6 moderately reduced the MMP-10 mRNA levels, whereas it significantly enhanced the MMP-10 protein mass in the A549 cells. This phenomenon mimicked the divergence of mRNA level and protein mass of MMP-10 in human NSCLC. Moreover, the present study indicated that IL-6 regulation of MMP-10 expression was via the JAK2/STAT3 pathway. STAT3 mRNA levels were significantly increased when the cells were treated with IL-6, whereas when AG490 (50 mu M) was added to the cell cultures, IL-6-induced increase of STAT3 mRNA levels was abolished. Meanwhile, AG490 blocked the IL-6-induced inhibition of MMP-10 mRNA as well as blocking the IL-6-induced increase of MMP-10 protein mass in the A549 cells. Neither IL-6 nor AG490 influenced JAK2 mRNA levels in the A549 cell cultures. It is concluded that the JAK2/STAT3 pathway is involved in the IL-6-mediated regulation of MMP-10, and IL-6 can moderately reduce MMP-10 mRNA levels and strongly increase MMP-10 protein mass in human lung adenocarcinoma A549 cells. Contrasting effects of IL-6 on MMP-10 mRNA level and protein concentration in A549 cells may partially explain the divergence of MMP-10 mRNA level and protein mass in human NSCLC.
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| 5. |
- Clark, Andrew G., et al.
(author)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Journal article (peer-reviewed)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
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| 6. |
- Gudmundsson, Valur, et al.
(author)
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Fully Depleted UTB and Trigate N-Channel MOSFETs Featuring Low-Temperature PtSi Schottky-Barrier Contacts With Dopant Segregation
- 2009
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In: IEEE Electron Device Letters. - 0741-3106 .- 1558-0563. ; 30:5, s. 541-543
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Journal article (peer-reviewed)abstract
- Schottky-barrier source/drain (SB-S/D) presents a promising solution to reducing parasitic resistance for device architectures such as fully depleted UTB, trigate, or FinFET. In this letter, a low-temperature process (<= 700 degrees C) with PtSi-based S/D is examined for the fabrication of n-type UTB and trigate FETs on SOI substrate (t(si) = 30 nm). Dopant segregation with As was used to achieve the n-type behavior at implantation doses of 1 (.) 10(15) and 5. 10(15) cm(-2). Similar results were found for UTB devices with both doses, but trigate devices with the larger dose exhibited higher on currents and smaller process variation than their lower dose counterparts.
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| 7. |
- Hu, Jinhong, et al.
(author)
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Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults
- 2008
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Journal article (peer-reviewed)abstract
- BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
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| 8. |
- Luo, Guanghua, et al.
(author)
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Genotyping of single nucleotide polymorphisms using base-quenched probe: A method does not invariably depend on the deoxyguanosine nucleotide
- 2009
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In: Analytical Biochemistry. - : Elsevier BV. - 1096-0309 .- 0003-2697. ; 386:2, s. 161-166
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Journal article (peer-reviewed)abstract
- Most available methods for detecting single nucleotide polymorphisms (SNPs) are based principally on the system that can produce an increased fluorescence signal during hybridization. In the current study, we demonstrate a method of base-quenched probe for polymerase chain reaction (PCR) genotyping that requires only a pair of primers and one fluorescent probe and does not invariably depend on the deoxyguanosine nucleotide. This method further exploits the phenomenon of fluorescence quenching of fluorescent-labeled probe during hybridization to its complementary target gene's sequence. 6-Carboxyfluorescein (FAM) can be directly conjugated to a base of either adenine (A), thymine (T), cytosine (C), or guanine (G), referred to as A-, T-, C-, or G-quenched probe, respectively, at either the 5' or 3' end. For describing the method in detail, we chose apolipoprotein M (apoM) as a target gene in the current study. DNA sequencing analyses validated that all four types of base-quenched probes could provide unbiased genotyping results (K = 1, P = 0.000), although the maximum speed of fluorescence increase, max(dF/dT), when using the G-quenched probe method, was approximately twofold lower than the others (P < 0.0001). Moreover, we applied this method to detect another seven SNPs in the genomes of phospholipase A2, monocyte chemoattractant protein I (MCP1), and L-ficolin, further confirming our method. It is concluded that this method is precise, simple, and economic as well as suitable for large-scale genotyping Studies. (C) 2008 Elsevier Inc. All rights reserved.
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| 9. |
- Pang, Jun-Feng, et al.
(author)
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mtDNA data indicate a single origin for dogs south of Yangtze River, less than 16,300 years ago, from numerous wolves.
- 2009
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In: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 26:12, s. 2849-64
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Journal article (peer-reviewed)abstract
- There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.
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| 10. |
- Zhang, Wen-Chao, et al.
(author)
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Clinical and pathological analysis of malignant carotid body tumour : a report of nine cases
- 2009
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In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 129:11, s. 1320-1325
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Journal article (peer-reviewed)abstract
- Conclusions. Malignant carotid body tumour (MCBT) is a clinically rare disease that often invades the carotid artery and cranial nerves. Diagnosis of malignant tumour should be based on extensive invasion of neighbouring organs and distant metastasis. Extensive resection should be undertaken early. Radiotherapy is effective, whereas chemotherapy is uncertain. Objective. To summarize the clinical pathological and prognostic characteristics of MCBT and explore methods for diagnosis and treatment. Materials and methods. The study material comprised clinical, pathological, therapeutic and follow-up data concerning nine patients (four males, five females) with MCBT, treated at Tianjin Cancer Hospital between January 1956 and June 2006. The material was analysed retrospectively. Disease duration averaged 6.4 years. Shamblin classification was: one case, type ?; 8 cases, type ?. All nine patients underwent ultrasound examination, four underwent digital subtraction arteriography (DSA) and three had magnetic resonance angiography (MRA). Five patients underwent preoperative training of compression of the carotid (Matas test). Extensive resection was performed in all nine cases. Results. The carotid artery was blocked in three patients. In one of these the artery was reconstructed with a vascular prosthesis, while two underwent carotid ligation. Eight patients suffered from a cranial nerve dysfunction (defect) and two suffered postoperatively from a hoarse voice, four had a glossal deviation, five had Horner's syndrome and one had a deviation of the lip angle. One patient had a congestive cough. The histopathological diagnosis in all nine cases was MCBT. One patient had metastases to a cervical lymph node and lung and another had liver metastasis. The median follow-up period was 3 years (range 6 months to 14 years). Six patients survived surgery, of whom two underwent radiotherapy. Two patients died and one could not be traced.
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