1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2. |
- Ablikim, M., et al.
(författare)
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Observation of the decay psi(3686) -> Lambda(Sigma)over-bar(+/-) pi(-/+) + c.c
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112007-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1:06 X 10(8) psi(3686) events collected with the BESIII detector, we present the first observation of the decays of psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c. and psi(3686) -> Lambda(Sigma) over bar (-) pi(+) + c.c. The branching fractions are measured to be B(psi(3686) -> Lambda(Sigma) over bar (+) pi(-) + c.c.) = (1.40 +/- 0.03 +/- 0.13) X 10(-4) and B(psi(3686) -> Lambda (Sigma) over bar (-) pi(+) + c.c.) = (1.54 +/- 0.04 +/- 0.13) X 10(-4) where the first errors are statistical and the second ones systematic.
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3. |
- Ablikim, M., et al.
(författare)
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Search for eta(c)(2S)h(c) -> p(p)over-bar decays and measurements of the chi(cJ) -> p(p)over-bar branching fractions
- 2013
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Ingår i: Physical Review D. - 1550-7998 .- 1550-2368. ; 88:11, s. 112001-
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Tidskriftsartikel (refereegranskat)abstract
- Using a sample of 1.06 x 10(8)psi(3686) events collected with the BESIII detector at BEPCII, the decays eta(c)(2S) -> p (p) over bar and h(c) -> p (p) over bar are searched for, where eta(c)(2S) and h(c) are reconstructed in the decay chains psi(3686) -> gamma eta(c)(2S), eta(c)(2S) -> p (p) over bar and psi(3686) -> pi(0)h(c), h(c) -> p (p) over bar, respectively. No significant signals are observed. The upper limits of the product branching fractions are determined to be B(psi(3686) -> gamma eta(c)(2S)) x B(eta(c)(2S) -> p (p) over bar) < 1.4 x 10(-6) and B(psi(3686) -> pi(0)h(c)) x B(h(c) -> p<(p)over bar>) < 1.3 x 10(-7) at the 90% C.L.. The branching fractions for chi(cJ) -> p<(p)over bar> (J = 0, 1, 2) are also measured to be (24.5 +/- 0.8 +/- 1.3, 8.6 +/- 0.5 +/- 0.5, 8.4 +/- 0.5 +/- 0.5) x 10(-5), which are the world's most precise measurements.
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4. |
- An, Junghwa, et al.
(författare)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 October 2009-30 November 2009
- 2010
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Ingår i: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 10:2, s. 404-408
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Tidskriftsartikel (refereegranskat)abstract
- This article documents the addition of 411 microsatellite marker loci and 15 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Acanthopagrus schlegeli, Anopheles lesteri, Aspergillus clavatus, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus terreus, Branchiostoma japonicum, Branchiostoma belcheri, Colias behrii, Coryphopterus personatus, Cynogolssus semilaevis, Cynoglossus semilaevis, Dendrobium officinale, Dendrobium officinale, Dysoxylum malabaricum, Metrioptera roeselii, Myrmeciza exsul, Ochotona thibetana, Neosartorya fischeri, Nothofagus pumilio, Onychodactylus fischeri, Phoenicopterus roseus, Salvia officinalis L., Scylla paramamosain, Silene latifo, Sula sula, and Vulpes vulpes. These loci were cross-tested on the following species: Aspergillus giganteus, Colias pelidne, Colias interior, Colias meadii, Colias eurytheme, Coryphopterus lipernes, Coryphopterus glaucofrenum, Coryphopterus eidolon, Gnatholepis thompsoni, Elacatinus evelynae, Dendrobium loddigesii Dendrobium devonianum, Dysoxylum binectariferum, Nothofagus antarctica, Nothofagus dombeyii, Nothofagus nervosa, Nothofagus obliqua, Sula nebouxii, and Sula variegata. This article also documents the addition of 39 sequencing primer pairs and 15 allele specific primers or probes for Paralithodes camtschaticus.
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5. |
- Qi, Xiuying, et al.
(författare)
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Prevalence and Correlates of Latent Autoimmune Diabetes in Adults in Tianjin, China A population-based cross-sectional study
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:1, s. 66-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Data on latent autoimmune diabetes in adults (LADA) from population-based studies are sparse. We sought to investigate the prevalence and correlates of LADA. RESEARCH DESIGN AND METHODS: A total of 8,109 participants, who were aged >= 15 years and living in Tianjin, China, were assessed to identify individuals with type 2 diabetes (American Diabetes Association Criteria, 1997) and further to detect patients with LADA. LADA was ascertained by 1) the presence of type 2 diabetes and age >= 35 years, 2) the lack of a requirement for insulin at least 6 months after the diagnosis of type 2 diabetes, and 3) serum GAD antibody positivity. Data were analyzed using multinomial logistic regression with adjustment for potential confounders. RESULTS: Of all participants, 498 (6.1%) were patients with type 2 diabetes. Of them, 46 (9.2%) were found to have LADA. The prevalence of LADA was 0.6% (46 of 8,109), and tended to increase with age up to 50-59 years in all participants. The odds ratios (95% CI) of LADA related to hypertension, family history of diabetes, waist-to-hip ratio >= 0.85, and major stressful events were 1.93 (1.02-3.65), 17.59 (9.08-34.06), 5.37 (2.31-12.49), and 4.09 (1.75-9.52), respectively. CONCLUSIONS: The prevalence of LADA is similar to 9% in patients with type 2 diabetes. Hypertension, family history of diabetes, central obesity, and major stressful events may be associated with the occurrence of LADA.
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6. |
- Li, Yifei, et al.
(författare)
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Expression and clinical significance of FXYD3 in endometrial cancer
- 2014
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Ingår i: Oncology Letters. - : Spandidos Publications. - 1792-1074 .- 1792-1082. ; 8:2, s. 517-522
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Tidskriftsartikel (refereegranskat)abstract
- FXYD3 expression is upregulated in numerous cancer cell types. The present study compared the FXDY3 expression in normal endometrium, premalignant lesion and endometrial cancer tissue samples, and investigated the correlation between FXDY3 expression and clinicopathological features. FXYD3 expression was analyzed by streptavidin-peroxidase immunohistochemistry in 21 normal endometrial tissue samples, 18 atypical endometrial hyperplasia samples and 50 tissues obtained from patients diagnosed with endometrial cancer. The percentage of FXYD3-positive cell expression in the normal endometrium, atypical hyperplasia and endometrial cancer tissues samples was 0, 22, and 26%, respectively. The differences between the atypical hyperplasia and endometrial cancer groups were statistically significant when compared with the normal group (P=0.007 and P=0.037, respectively). There was no significant difference between the atypical hyperplasia and endometrial cancer groups. The percentage of FXYD3-positive cells correlated with the fertility frequency (Pless than0.05). In conclusion, FXYD3 is a potential biomarker for endometrial cancer, and its upregulation may be an early event in endometrial carcinoma progression. In addition, FXYD3 expression in endometrial carcinoma correlates with fertility frequency.
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7. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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8. |
- Xu, Caihua, et al.
(författare)
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WT1 promotes cell proliferation in non-small cell lung cancer cell lines through up-regulating cyclin D1 and p-pRb in vitro and in vivo
- 2013
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Ingår i: PLOS ONE. - San Francisco : PLoS, Public Library of Science. - 1932-6203. ; 8:8
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Tidskriftsartikel (refereegranskat)abstract
- The Wilms' tumor suppressor gene (WT1) has been identified as an oncogene in many malignant diseases such as leukaemia, breast cancer, mesothelioma and lung cancer. However, the role of WT1 in non-small-cell lung cancer (NSCLC) carcinogenesis remains unclear. In this study, we compared WT1 mRNA levels in NSCLC tissues with paired corresponding adjacent tissues and identified significantly higher expression in NSCLC specimens. Cell proliferation of three NSCLC cell lines positively correlated with WT1 expression; moreover, these associations were identified in both cell lines and a xenograft mouse model. Furthermore, we demonstrated that up-regulation of Cyclin D1 and the phosphorylated retinoblastoma protein (p-pRb) was mechanistically related to WT1 accelerating cells to S-phase. In conclusion, our findings demonstrated that WT1 is an oncogene and promotes NSCLC cell proliferation by up-regulating Cyclin D1 and p-pRb expression.
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9. |
- Amos, Christopher I, et al.
(författare)
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Genome-wide association study identifies novel loci predisposing to cutaneous melanoma
- 2011
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 20:24, s. 23-5012
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Tidskriftsartikel (refereegranskat)abstract
- We performed a multistage genome-wide association study of melanoma. In a discovery cohort of 1804 melanoma cases and 1026 controls, we identified loci at chromosomes 15q13.1 (HERC2/OCA2 region) and 16q24.3 (MC1R) regions that reached genome-wide significance within this study and also found strong evidence for genetic effects on susceptibility to melanoma from markers on chromosome 9p21.3 in the p16/ARF region and on chromosome 1q21.3 (ARNT/LASS2/ANXA9 region). The most significant single-nucleotide polymorphisms (SNPs) in the 15q13.1 locus (rs1129038 and rs12913832) lie within a genomic region that has profound effects on eye and skin color; notably, 50% of variability in eye color is associated with variation in the SNP rs12913832. Because eye and skin colors vary across European populations, we further evaluated the associations of the significant SNPs after carefully adjusting for European substructure. We also evaluated the top 10 most significant SNPs by using data from three other genome-wide scans. Additional in silico data provided replication of the findings from the most significant region on chromosome 1q21.3 rs7412746 (P = 6 × 10(-10)). Together, these data identified several candidate genes for additional studies to identify causal variants predisposing to increased risk for developing melanoma.
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10. |
- Bu, Zhaojun, et al.
(författare)
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Performance of four mosses in a reciprocal transplant experiment : implications for peatland succession in NE China
- 2013
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Ingår i: Journal of Bryology. - 0373-6687 .- 1743-2820. ; 35, s. 220-227
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Tidskriftsartikel (refereegranskat)abstract
- Sphagnum dominates the moss layer in northern peatlands, but its dominance has decreased while there has been an expansion of other moss genera in some peatlands of NE China since the 1960s. To discover the mechanisms underlying this succession, we performed a four-month reciprocal transplant experiment in Hani Peatland with three Sphagnum species, Sphagnum palustre, S. magellanicum, and S. fuscum and one other moss Polytrichum strictum. Performance of the four mosses and the environmental factors: height above water table (HWT), vascular plant cover and pH, electrical conductivity, base cations, and N and P concentrations in water in the four moss habitats were measured. Biomass production in S. palustre was negatively affected by HWT. Phosphorus had a positive effect on biomass production in S. magellanicum and Polytrichum. None of the environmental factors had any effect on S. fuscum. Overall, the three Sphagnum species deteriorated in P. strictum hummocks, while P. strictum exhibited a wider ecological amplitude and maintained or increased its vigour levels in Sphagnum hummocks. Biomass production in S. palustre and S. magellanicum was negatively affected by P. strictum indicating the competitive ability of P. strictum. Our results suggest that its wide ecological amplitude and competitive ability may explain why P. strictum can expand and replace Sphagnum in some northern peatlands.
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11. |
- Carlsson-Jonsson, Anna, et al.
(författare)
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N-terminal truncations of substance P1-7 amide affect its action on spinal cord injury-induced mechanical allodynia in rats
- 2014
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 738, s. 319-325
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Tidskriftsartikel (refereegranskat)abstract
- Central neuropathic pain can arise from injury of the spinal cord and can become chronic. Treatment is difficult and, because complete pain relief is currently very hard to achieve, there is a need for new, more effective treatment options. In this study we used an animal model of spinal cord injury to evaluate the potency of a bioactive fragment of substance P (SP), i.e. SP1-7, in alleviating signs of allodynia and acute pain. SP1-7 is known from earlier studies to possess antinociceptive properties. We also studied the effects of intraperitoneal injection of an amidated analog of this heptapeptide and of its truncated analogs, all of which had high affinity to the SP1-7 binding site, to evaluate the importance of the removed amino acids for the bioclistribution and stability of the peptides. Most of the examined compounds alleviated mechanical alloclynia without any signs of sedation or motor impairment in the rats. In contrast, the response threshold to acute nociceptive stimulation was not affected by arty of the compounds tested. Most of the amino acids in the heptapepticle structure were essential for retaining the biological effect after peripheral injection. These observations suggest that the heptapepticle and its N-Lerminal truncated hexa- and pentapeptide analogs could be of interest for further development of analgesics in the management of mechanical allodynia.
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12. |
- Chen, Lin, et al.
(författare)
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Seismically constrained thermo-rheological structure of the eastern Tibetan margin : Implication for lithospheric delamination
- 2014
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Ingår i: Tectonophysics. - : Elsevier. - 0040-1951 .- 1879-3266. ; 627, s. 122-134
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Tidskriftsartikel (refereegranskat)abstract
- The eastern Tibetan margin bordered by the Longmen Shan range exhibits significant lateral differences in the lithospheric structure and thermal state. To investigate the roles of these differences in mountain building, we construct a thermo-rheological model along a wide-angle seismic profile across the eastern Tibetan margin based on recent seismic and thermal observations. The thermal modeling is constrained by the surface heat flow data and crustal P wave velocity model. The construction of the theological envelopes is based on rock mechanics results, and involves two types of rheology: a weak case where the lower crust is felsic granulite and the lithospheric mantle is wet peridotite, and a strong case where the lower crust is mafic granulite and the lithospheric mantle is dry peridotite. The results demonstrate: (1) one high-temperature anomaly exists within the uppermost mantle beneath eastern Tibet, indicating that the crust in eastern Tibet is remarkably warmer than that in the Sichuan basin, and (2) the rheological strength of the lithospheric mantle beneath eastern Tibet is considerably weaker than that beneath the Sichuan basin. The rheological profiles are in accord with seismicity distribution. By combining these results with the observed crustal/lithospheric architecture, Pn velocity distribution and magmatism in the eastern Tibetan margin, we suggest that the delamination of a thickened lithospheric mantle root beneath eastern Tibet is responsible for the growth of the eastern Tibetan margin.
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13. |
- Guo, Jing, et al.
(författare)
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Prediction of variability of precipitation in the Yangtze River Basin under the climate change conditions based on automated statistical downscaling
- 2012
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Ingår i: Stochastic environmental research and risk assessment (Print). - : Springer Science and Business Media LLC. - 1436-3240 .- 1436-3259. ; 26:2, s. 157-176
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Tidskriftsartikel (refereegranskat)abstract
- Many impact studies require climate change information at a finer resolution than that provided by general circulation models (GCMs). Therefore the outputs from GCMs have to be downscaled to obtain the finer resolution climate change scenarios. In this study, an automated statistical downscaling (ASD) regression-based approach is proposed for predicting the daily precipitation of 138 main meteorological stations in the Yangtze River basin for 2010-2099 by statistical downscaling of the outputs of general circulation model (HadCM3) under A2 and B2 scenarios. After that, the spatial-temporal changes of the amount and the extremes of predicted precipitation in the Yangtze River basin are investigated by Mann-Kendall trend test and spatial interpolation. The results showed that: (1) the amount and the change pattern of precipitation could be reasonably simulated by ASD; (2) the predicted annual precipitation will decrease in all sub-catchments during 2020s, while increase in all sub-catchments of the Yangtze River Basin during 2050s and during 2080s, respectively, under A2 scenario. However, they have mix-trend in each sub-catchment of Yangtze River basin during 2020s, but increase in all sub-catchments during 2050s and 2080s, except for Hanjiang River region during 2080s, as far as B2 scenario is concerned; and (3) the significant increasing trend of the precipitation intensity and maximum precipitation are mainly occurred in the northwest upper part and the middle part of the Yangtze River basin for the whole year and summer under both climate change scenarios and the middle of 2040-2060 can be regarded as the starting point for pattern change of precipitation maxima.
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14. |
- Guo, Jing, et al.
(författare)
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Pulmonary toxicity and adjuvant effect of di-(2-exylhexyl) phthalate in ovalbumin-immunized BALB/c mice
- 2012
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Asthma is a complex pulmonary inflammatory disease, which is characterized by airway hyperresponsiveness, variable airflow obstruction and inflammation in the airways. The majority of asthma is allergic asthma, which is a disease caused by type I hypersensitivity mediated by IgE. Exposures to a number of environmental chemicals are suspected to lead to asthma, one such pollutant is di-(2-ethylheyl) phthalate (DEHP). DEHP is a manufactured chemical that is commonly added in plastic products to make them flexible. Epidemiological studies have revealed a positive association between DEHP exposure and asthma prevalence.METHODOLOGY/PRINCIPAL FINDINGS: The present study was aimed to determine the underlying role of DEHP exposure in airway reactivity, especially when combined with allergen exposure. The biomarkers include pulmonary histopathology, airway hyperresponsiveness (lung function), IgE, IL-4, IFN-γ and eosinophils. Healthy balb/c mice were randomly divided into eight exposure groups (n = 8 each): (1) saline control, (2) 30 µg/(kg•d) DEHP, (3) 300 µg/(kg•d) DEHP, (4) 3000 µg/(kg•d) DEHP, and (5) ovalbumin (OVA)-sensitized group, (6) OVA-combined with 30 µg/(kg•d) DEHP, (7) OVA-combined with 300 µg/(kg•d) DEHP, and (8) OVA-combined with 3000 µg/(kg•d) DEHP. Experimental tests were conducted after 52-day DEHP exposure and subsequently one week of challenge with aerosolized OVA. The principal findings include: (1) Strong postive associations exist between OVA-combined DEHP exposure and serum total IgE (T-IgE), as well as histological findings. These positive associations show a dose-dependent low dose sensitive effect of DEHP. (2) IL-4, eosinophil recruitment and lung function are also indicators for adjuvant effect of DEHP.CONCLUSIONS/SIGNIFICANCE: Our results suggest that except the significant changes of immunological and inflammatory biomarkers (T-IgE, IL-4, IFN-γ and eosinophils), the pulmonary histological (histopathological examination) and physiological (lung function) data also support that DEHP may promote and aggravate allergic asthma by adjuvant effect.
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15. |
- Han, Jing, et al.
(författare)
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The expression of p-ATF2 involved in the chondeocytes apoptosis of an endemic osteoarthritis, Kashin-Beck disease
- 2013
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Ingår i: BMC Musculoskeletal Disorders. - : BioMed Central. - 1471-2474. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of the study was to understand the function and expression of ATF2 by JNK and p38 signal pathways in the chondrocytes apoptosis of articular cartilage of the Kashin-Beck disease (KBD).METHODS: The changes of ATF2, JNK and p38 mRNAs and proteins were investigated between cartilage and chondrocyte as well as KBD and normal. JNK and p38 inhibitors were used as treatments to prevent apoptosis in chondrocytes from KBD patients.RESULTS: It was found that the protein levels of p-p38, p-JNK, ATF2 and p-ATF2 increased in KBD human cartilage which is in line with the higher mRNA levels of p38, JNK and ATF2 as compared both with normal cartilage and KBD chondrocytes. In addition, p-ATF2 was only detected in KBD cartilage. Furthermore, JNK inhibitor was more effective than p38 inhibitor in preventing chondrocyte apoptosis at equal concentrations of 10 μM.CONCLUSION: These findings indicated the expression of p-ATF2 by JNK and p38 signal pathways involved in the chondrocyte apoptosis in cartilage with KBD.
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16. |
- Han, Yang, et al.
(författare)
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X-radiation inhibits histone deacetylase 1 and 2, upregulates Axin expression and induces apoptosis in non-small cell lung cancer
- 2012
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Ingår i: Radiation Oncology. - : BioMed Central. - 1748-717X. ; 7:183
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHistone deacetylase (HDAC) plays an important role in the deacetylation of histone, which can alter gene expression patterns and affect cell behavior associated with malignant transformation. The aims of this study were to investigate the relationships between HDAC1, HDAC2, clinicopathologic characteristics, patient prognosis and apoptosis, to clarify the mechanism of upregulation of the Axis inhibitor Axin (an important regulator of the Wnt pathway) by X-radiation and to elucidate the effect of siRNA on radiation therapy of non-small cell lung cancer (NSCLC).MethodsHDAC1 and HDAC2 expression levels were measured by immunohistochemistry and reverse transcription PCR. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP-nick end labeling and fluorescence activated cell sorting. BE1 cells expressing Axin were exposed to 2 Gy of X-radiation.ResultsExpression of HDAC1 and that of HDAC2 were correlated, and significantly higher in NSCLC tissues than in normal lung tissues (P < 0.05). HDAC1 and HDAC2 expression was correlated with pTNM stage and negatively correlated with differentiation of NSCLC and apoptotic index (P < 0.05). The prognosis of patients with low expression of HDAC1 and HDAC2 was better than that of those with high expression. X-radiation and siRNA inhibited HDAC1 and HDAC2 expression in NSCLC cells and Axin levels were significantly higher in BE1 cells.ConclusionsX-radiation and siRNA inhibit expression of HDAC1 and HDAC2, weaken the inhibitory effect of HDAC on Axin, upregulate Axin expression and induce apoptosis of lung cancer cells. Inhibition of HDAC1 and HDAC2 is a means of enhancing the radiosensitivity of NSCLC.
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17. |
- Hua, Chen, et al.
(författare)
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Downscaling GCMs using the Smooth Support Vector Machine method to predict daily precipitation in the Hanjiang Basin
- 2010
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Ingår i: Advances in Atmospheric Sciences. - : Springer Science and Business Media LLC. - 0256-1530 .- 1861-9533. ; 27:2, s. 274-284
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Tidskriftsartikel (refereegranskat)abstract
- General circulation models (GCMs) are often used in assessing the impact of climate change at global and continental scales. However, the climatic factors simulated by GCMs are inconsistent at comparatively smaller scales, such as individual river basins. In this study, a statistical downscaling approach based on the Smooth Support Vector Machine (SSVM) method was constructed to predict daily precipitation of the changed climate in the Hanjiang Basin. NCEP/NCAR reanalysis data were used to establish the statistical relationship between the larger scale climate predictors and observed precipitation. The relationship obtained was used to project future precipitation from two GCMs (CGCM2 and HadCM3) for the A2 emission scenario. The results obtained using SSVM were compared with those from an artificial neural network (ANN). The comparisons showed that SSVM is suitable for conducting climate impact studies as a statistical downscaling tool in this region. The temporal trends projected by SSVM based on the A2 emission scenario for CGCM2 and HadCM3 were for rainfall to decrease during the period 2011-2040 in the upper basin and to increase after 2071 in the whole of Hanjiang Basin.
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18. |
- Huang, Jing, et al.
(författare)
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Improved Performance of Colloidal CdSe Quantum Dot-Sensitized Solar Cells by Hybrid Passivation
- 2014
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 6:21, s. 18808-18815
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Tidskriftsartikel (refereegranskat)abstract
- A hybrid passivation strategy is employed to modify the surface of colloidal CdSe quantum dots (QDs) for quantum dot-sensitized solar cells (QDSCs), by using mercaptopropionic acid (MPA) and iodide anions through a ligand exchange reaction in solution. This is found to be an effective way to improve the performance of QDSCs based on colloidal QDs. The results show that MPA can increase the coverage of the QDs on TiO2 electrodes and facilitate the hole extraction from the photoxidized QDs, and simultaneously, that the iodide anions can remedy the surface defects of the CdSe QDs and thus reduce the recombination loss in the device. This hybrid passivation treatment leads to a significant enhancement of the power conversion efficiency of the QDSCs by 41%. Furthermore, an optimal ratio of iodide ions to MPA was determined for favorable hybrid passivation; results show that excessive iodine anions are detrimental to the loading of the QDs. This study demonstrates that the improvement in QDSC performance can be realized by using a combination of different functional ligands to passivate the QDs, and that ligand exchange in solution effective approach to introduce can be an different ligands.
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19. |
- Jing Xu, Wei, et al.
(författare)
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Improved Filter Bank Approach for the Design of Variable Bandedge and Fractional Delay Filters
- 2014
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Ingår i: IEEE Transactions on Circuits and Systems Part 1. - : Institute of Electrical and Electronics Engineers (IEEE). - 1549-8328 .- 1558-0806. ; 61:3, s. 764-777
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Tidskriftsartikel (refereegranskat)abstract
- The paper proposes an optimization technique for the design of variable digital filters with simultaneously tunable bandedge and fractional delay using a fast filter bank (FFB) approach. In the FFB approach, full band signals are split into multibands, and each band is multiplied by a proper phase shift to realize the variable fractional delay. In the proposed technique, in the formulation of the optimization of the 0th stage prototype filter of the FFB, the ripples of the filters in the subsequent stages are all taken into consideration. In addition, a shaping filter is applied to the last retained band of the FFB to form the transition band of the variable filter, such that the transition width of each band in the FFB can be relaxed to reduce the computational complexity. In total three shaping filters, constructed from a prototype filter, can be shared by different bands, so that the extra cost incurred due to the shaping filter is low.
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20. |
- Lango Allen, Hana, et al.
(författare)
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Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
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21. |
- Li, Lili, et al.
(författare)
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Heparanase overexpression reduces carrageenan-induced mechanical and cold hypersensitivity in mice
- 2012
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 511:1, s. 4-7
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Tidskriftsartikel (refereegranskat)abstract
- Heparanase controls the structure and functions of extracellular matrix (ECM) by degrading heparan sulfate proteoglycans. Heparanase is involved in inflammatory process through modulating the functions of inflammatory cytokines. The present study aimed to find out whether overexpression of heparanase in mice affects carrageenan-induced localized inflammation and inflammatory hyperalgesia. Without challenge, the heparanase overexpression did not significantly affect the mice in response to mechanical, cold and heat stimulation. Unilateral subcutaneous administration of carrageenan produced hypersensitivity to mechanical and cold in both wildtype and the heparanase overexpression (Hpa-tg) mice 24h after treatment. In comparison to wildtype animals, the Hpa-tg mice showed significantly reduced mechanical and cold hypersensitivity. This may, at least partially, due to the reduced mast cell infiltration at the site of inflammation in Hpa-tg mice. These data support a role for heparanase that reduces localized inflammation and inflammatory hyperalgesia in mice.
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22. |
- Liu, Chang, et al.
(författare)
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NHE8 plays an important role in mucosal protection via its effect on bacterial adhesion.
- 2013
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Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 1522-1563 .- 0363-6143. ; 305:1
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Tidskriftsartikel (refereegranskat)abstract
- The Na(+)/H(+) exchanger NHE8 is expressed on the apical membrane of intestinal epithelial cells and is particularly abundant in the colon. Our previous study showed that Muc2 expression was significantly reduced in NHE8-knockout (NHE8(-/-)) mice, suggesting that NHE8 plays a role in mucosal protection in the colon. The current study confirms and extends our studies on the role of NHE8 in mucosal protection. The number of bacteria attached on the distal colon was significantly increased in NHE8(-/-) mice compared with their wild-type littermates. As expected, IL-4 expression was markedly increased in NHE8(-/-) mice compared with wild-type mice. Immunohistochemistry showed disorganization in the mucin layer of NHE8(-/-) mice, suggesting a possible direct bacteria-epithelia interaction. Furthermore, NHE8(-/-) mice were susceptible to dextran sodium sulfate-induced mucosal injury. In wild-type mice, dextran sodium sulfate treatment inhibited colonic NHE8 expression. In Caco-2 cells, the absence of NHE8 expression resulted in higher adhesion rates of Salmonella typhimurium but not Lactobacillus plantarum. Similarly, in vivo, S. typhimurium adhesion rate was increased in NHE8(-/-) mice compared with wild-type mice. Our study suggests that NHE8 plays important roles in protecting intestinal epithelia from infectious bacterial adherence.
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23. |
- Okada, Yukinori, et al.
(författare)
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Genetics of rheumatoid arthritis contributes to biology and drug discovery
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 506:7488, s. 376-381
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Tidskriftsartikel (refereegranskat)abstract
- A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA)(1). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating similar to 10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2-4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation(5), cis-acting expression quantitative trait loci(6) and pathway analyses(7-9)-as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes-to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.
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24. |
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25. |
- Schumacher, Fredrick R., et al.
(författare)
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Genome-wide association study identifies new prostate cancer susceptibility loci
- 2011
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Ingår i: Human Molecular Genetics. - London : IRL Press. - 0964-6906 .- 1460-2083. ; 20:19, s. 3867-3875
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PrCa) is the most common non-skin cancer diagnosed among males in developed countries and the second leading cause of cancer mortality, yet little is known regarding its etiology and factors that influence clinical outcome. Genome-wide association studies (GWAS) of PrCa have identified at least 30 distinct loci associated with small differences in risk. We conducted a GWAS in 2782 advanced PrCa cases (Gleason grade >= 8 or tumor stage C/D) and 4458 controls with 571 243 single nucleotide polymorphisms (SNPs). Based on in silico replication of 4679 SNPs (Stage 1, P < 0.02) in two published GWAS with 7358 PrCa cases and 6732 controls, we identified a new susceptibility locus associated with overall PrCa risk at 2q37.3 (rs2292884, P = 4.3 x 10(-8)). We also confirmed a locus suggested by an earlier GWAS at 12q13 (rs902774, P = 8.6 x 10(-9)). The estimated per-allele odds ratios for these loci (1.14 for rs2292884 and 1.17 for rs902774) did not differ between advanced and non-advanced PrCa (case-only test for heterogeneity P = 0.72 and P = 0.61, respectively). Further studies will be needed to assess whether these or other loci are differentially associated with PrCa subtypes.
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