| 1. |
- Birney, Ewan, et al.
(författare)
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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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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)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. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Tian, Chao, et al.
(författare)
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Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients
- 2007
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Ingår i: World Journal of Gastroenterology. - 1007-9327 .- 2219-2840. ; 13:28, s. 3878-3882
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To clarify the expression change of Wnt-induced secreted protein-1 (WISP-1) in human rectal cancer and to determine whether it is correlated with invasion and metastasis of human rectal cancer. Methods: Eighty-six paired samples of rectal cancer and surgically resected distant normal rectal tissue were collected and allocated into cancer group and control group respectively. WISP-1 mRNA was detected by relative quantitative real-time RT-PCR and WISP-1 protein was examined by immunohistochemical staining. Results: WISP-1 gene overexpression was found in 65% (56/86) primary rectal cancers, 2-30 times that of the level in normal matched rectal tissues (P = 0.001). The mRNA expression level was correlated with Duke's staging, histological differentiation grade and lymph node status. The WISP-1 protein expression was in accordance with mRNA expression level. The positive degree of immunohistochemical staining in the cancer group (1.40 ± 0.35) was different from that in control group (1.04 ± 0.08, P < 0.001). Moreover, in cancer group the positive staining degree in high-level mRNA cancers (1.46 ± 0.37, n = 56) was higher than that in low-level mRNA (1.28 ± 0.28, n = 30, P = 0.018). Conclusion: Aberrant levels of WISP-1 expression may play a role in rectal tumorigenesis. WISP-1 may be used as a specific clinical diagnosis and prognosis marker in rectal cancer. © 2007 WJG. All rights reserved.
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| 4. |
- Hu, Jinhong, et al.
(författare)
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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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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:4
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Meng, Wen-Jian, et al.
(författare)
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Microsatellite instability did not predict individual survival in sporadic stage II and III rectal cancer patients
- 2007
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 72:1-2, s. 82-88
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Tumors with high-frequency microsatellite instability (MSI-H) have unique biological behavior and the predictive role of microsatellite instability (MSI) status on survival of colorectal cancer is still debated. The prognostic significance of MSI status in sporadic stage II and III rectal cancer patients needs to be more precisely defined. So we investigated the relationship between MSI status and clinicopathological features and prognosis in these patients. Methods: DNAs from fresh-frozen paired samples of tumors and corresponding normal tissue from 128 stage II and III rectal cancer patients were analyzed for MSI by PCR amplification using markers recommended by a National Cancer Institute workshop on MSI. To assess prognostic significance, Cox proportional hazards modeling was used. Results: Twelve (9.3%) tumors in our study were MSI-H, 28 (21.9%) were low-frequency MSI (MSI-L) and 88 (68.8%) were microsatellite stable (MSS). Most of the MSI-H tumors compared with MSI-L and MSS tumors were found in female patients (p = 0.031), had mucinous histology (p = 0.023), high grade of differentiation (p = 0.002) and high level of preoperative serum carcinoembryonic antigen (p = 0.005). Rectal cancer patients with MSI-H did not show a better clinical outcome than those with MSI-L/MSS, neither in all cases (p = 0.986) nor in stage II and stage III disease analyzed separately (p = 0.705 and p = 0.664, respectively). Conclusions: Data provided here demonstrated there was high incidence of MSI-H and MSI was not a prognostic factor in sporadic stage II and III rectal cancers from the Chinese Han population included in this study. Tumor stage is more suitable than MSI status for prediction of individual survival in sporadic stage II and III rectal cancer patients. Copyright © 2007 S. Karger AG.
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| 6. |
- Pang, Jun-Feng, et al.
(författare)
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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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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 26:12, s. 2849-64
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 8. |
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| 9. |
- Wang, Chao-Jie, et al.
(författare)
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Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer
- 2009
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Ingår i: Disease Markers. - 0278-0240 .- 1875-8630. ; 26:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- We are just beginning to understand how microRNAs (miRNAs) are involved in tumor-related processes in humans. Applying real-time RT-PCR, we investigated the miR-31, miR-143 and miR-145 expression in 98 primary CRC specimens, along with the corresponding normal mucosa specimens, and analyze the relationship of their expression with clinicopathological features. Our results showed the miR-31 expression was up-regulated in CRC compared to normal mucosa (p = 0.001). Furthermore, miR-31 expression was positively related to advanced TNM stage (p = 0.026) and deeper invasion of tumors (p = 0.024). MiR-145 was down-regulated in both colon (p = 0.001) and rectal (p = 0.012) cancer. MiR-143 was only down-regulated in colon cancer (p = 0.023) but not in rectal cancer (p = 0.351). There was no relationship of miR-143 and miR-145 expression with other clinicopathological features (p > 0.05), except that the miR-145 expression was related to cancer site (p = 0.03). In conclusion, the miR-31 overexpression may be involved in the development and progression of CRC. The miR-143 and miR-145 may play a certain role in the development of colon and/or rectal cancers but not in progression of the disease.
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| 10. |
- Xu, Bing, et al.
(författare)
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Clinicopathological significance of caspase-8 and caspase-10 expression in rectal cancer
- 2008
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Ingår i: Oncology. - : S. Karger AG. - 0890-9091 .- 0030-2414 .- 1423-0232. ; 74:3-4, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. Methods: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. Results: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). Conclusions: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer. Copyright © 2008 S. Karger AG.
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