| 1. |
- Dastani, Zari, et al.
(författare)
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Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits : A Multi-Ethnic Meta-Analysis of 45,891 Individuals
- 2012
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 8:3, s. e1002607-
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Tidskriftsartikel (refereegranskat)abstract
- Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P=4.5 x 10(-8)-1.2 x 10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3 x 10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p=4.3 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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| 2. |
- Kang, Yu, et al.
(författare)
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On the Mechanism of Protein Adsorption onto Hydroxylated and Nonhydroxylated TiO2 Surfaces
- 2010
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Ingår i: The Journal of Physical Chemistry C. - Washington DC, USA : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 114:34, s. 14496-14502
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Tidskriftsartikel (refereegranskat)abstract
- Protein adsorption onto implant surfaces is of great importance for the regulation of implant bioactivity. Surface modification of implants is a promising way in the molecular design of biocompatible materials against nonspecific adsorption of proteins. On the basis of these fundamental facts, we focus in this work on the different behavior of protein adsorption on hydroxylated and nonhydroxylated rutile TiO2 (110) surfaces through molecular dynamics simulations. Our investigation indicates that the distribution of the water molecules at the interface induced by the surface modification plays an important role in the protein adsorption. The surface with modified hydroxyl groups was observed to have much greater affinity to the protein, as reflected by the larger protein-surface electrostatic interaction and by the larger amount of adsorbed residues. The highly ordered structure of the modified hydroxyl groups on the hydroxylated surface diminishes the possibility of hydrogen bond formation between the surface and the water molecules above it, which in turn makes it easier for the protein to move closer to the surface with hydroxyl modification.
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| 3. |
- Kubo, Takuya, et al.
(författare)
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Polymer-based photocoupling agent for the efficient immobilization of nanomaterials and small molecules
- 2011
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 27:15, s. 9372-9378
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Tidskriftsartikel (refereegranskat)abstract
- A highly efficient photocoupling agent, based on perfluorophenylazide (PFPA)-conjugated polyallylamine (PAAm), was developed for the efficient immobilization of polymers, nanoparticles, graphene, and small molecules. The conjugate, PAAm–PFPA, was synthesized, and the percentage of the photoactive moiety, PFPA, can be controlled by the ratio of the two components in the synthesis. By treating epoxy-functionalized wafers with PAAm–PFPA, photoactive surfaces were generated. Compared with the PFPA surface, these polymer-based photocoupling matrix resulted in significantly enhanced immobilization efficiencies, especially for nanomaterials and small molecules. Thus, polystyrene nanoparticles (PS NPs) and alkyl-functionalized silica nanoparticles (SNPs) were successfully immobilized on the PAAm–PFPA surface, resulting in a high material density. Graphene flakes patterned on the PAAm–PFPA surface showed improved feature resolution in addition to a higher material density compared to that of flakes immobilized on the PFPA surface. Furthermore, 2-O-α-d-mannopyranosyl-d-mannopyranose (Man2) immobilized on the PAAm–PFPA surface exhibited significantly enhanced signals when treated with lectin concanavalin A (Con A).
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| 4. |
- Li, Hong, et al.
(författare)
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A Switchable bis-Branched [1]Rotaxane featuring Dual-Mode Molecular Motions and Tunable Molecular Aggregation
- 2014
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Ingår i: ACS Applied Materials and Interfaces. - : American Chemical Society (ACS). - 1944-8244 .- 1944-8252. ; 6:21, s. 18921-18929
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Tidskriftsartikel (refereegranskat)abstract
- A multifunctional bis-branched [1]rotaxane containing a perylene bisimide (PBI) core and two identical bistable[1]rotaxane arms terminated with ferrocene units was prepared and characterized by H-1 NMR, C-13 NMR, and 2D ROESY NMR spectroscopies and by HR-ESI spectrometry. The system is shown to possess several key features: (1) In acetone solution, external acid base stimuli can result in relative mechanical movements of its ring and thread, which can induce extension and contraction movements of the whole system accompanied by a rotational movement of the ferrocene units, thus realizing dual-mode molecular motions, and the optimized conformations at different states are obtained through molecular dynamics simulations employing the general Amber force field. (2) The introduction of PBI enables the system fluorescence encoding through distance-dependent photoinduced electron transfer process from the ferrocene units to the PBI fluorophore. (3) The addition of Zn2+ can increase the degree of aggregation of the system, while adding base hinders aggregation because of the movement of the macrocyde. The tunable aggregated nanostructural morphologies of [1]rotaxane were examined by scanning electron microscopy. These results can pave the way to achieve precise control of integrated and coupling nanomechanical motions at a single-molecule level and provide more insight into controlling the aggregate behavior of switchable mechanically interlocked molecules.
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| 5. |
- Roy, Sushmita, et al.
(författare)
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Identification of functional elements and regulatory circuits by Drosophila modENCODE.
- 2010
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 330:6012, s. 1787-1797
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Tidskriftsartikel (refereegranskat)abstract
- To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation.
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| 6. |
- Xu, Weili, et al.
(författare)
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Detection of Prediabetes and Undiagnosed Type 2 Diabetes : A Large Population-Based Study
- 2012
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Ingår i: Canadian Journal of Diabetes. - : Elsevier BV. - 1499-2671. ; 36:3, s. 108-113
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prediabetes and undiagnosed diabetes have been commonly ignored. We aimed to investigate the prevalence of prediabetes and undiagnosed type 2 diabetes mellitus, and to verify the hypothesis that vascular risk factors (VRFs) may indicate prediabetes and undiagnosed type 2 diabetes.Methods: A total of 7567 adults, who were 20 to 79 years of age, and living in Tianjin, China, participated in this study. Type 2 diabetes was assessed based on medical history, hypoglycemic drugs use, fasting plasma glucose level >= 7.0 mmol/L, or postprandial 2-hour plasma glucose level >= 11.1 mmol/L. Undiagnosed type 2 diabetes was defined among subjects with type 2 diabetes when neither a medical history of diabetes nor hypoglycemic drugs use was present. Prediabetes was ascertained as fasting plasma glucose level of 6.1 to 6.9 mmol/L, or postprandial 2-hour plasma glucose level of 7.8 to 11.0 mmol/L (WHO 1999) among diabetes-free participants. Data were analyzed using multinomial logistic regression with adjustment for potential confounders.Results: Of all participants, 655 (8.7%) had prediabetes, and 721 (9.5%) were patients with type 2 diabetes, including 321 (4.2%) undiagnosed type 2 diabetes accounting for 44.5% patients with diabetes. The prevalence of prediabetes and undiagnosed type 2 diabetes increased with age, and was higher in women than in men. In a fully adjusted multinomial logistic regression model, hypertension, overweight, obesity, central obesity, and family history of diabetes were significantly associated with prediabetes and undiagnosed diabetes, whereas physical inactivity was independently related to undiagnosed diabetes.Conclusion: The prevalence of prediabetes and undiagnosed diabetes is approximately 13%, and almost 45% of patients with diabetes are undiagnosed. VRFs, such as hypertension, high adiposity, and family history of diabetes can be indicators for detecting prediabetes and undiagnosed diabetes.
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| 7. |
- Yan, Weirong, et al.
(författare)
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ISS - An Electronic Syndromic Surveillance System for Infectious Disease in Rural China
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:4, s. e62749-
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Tidskriftsartikel (refereegranskat)abstract
- Background: syndromic surveillance system has great advantages in promoting the early detection of epidemics and reducing the necessities of disease confirmation, and it is especially effective for surveillance in resource poor settings. However, most current syndromic surveillance systems are established in developed countries, and there are very few reports on the development of an electronic syndromic surveillance system in resource-constrained settings. Objective: this study describes the design and pilot implementation of an electronic surveillance system (ISS) for the early detection of infectious disease epidemics in rural China, complementing the conventional case report surveillance system. Methods: ISS was developed based on an existing platform 'Crisis Information Sharing Platform' (CRISP), combining with modern communication and GIS technology. ISS has four interconnected functions: 1) work group and communication group; 2) data source and collection; 3) data visualization; and 4) outbreak detection and alerting. Results: As of Jan. 31st 2012, ISS has been installed and pilot tested for six months in four counties in rural China. 95 health facilities, 14 pharmacies and 24 primary schools participated in the pilot study, entering respectively 74256, 79701, and 2330 daily records into the central database. More than 90% of surveillance units at the study sites are able to send daily information into the system. In the paper, we also presented the pilot data from health facilities in the two counties, which showed the ISS system had the potential to identify the change of disease patterns at the community level. Conclusions: The ISS platform may facilitate the early detection of infectious disease epidemic as it provides near real-time syndromic data collection, interactive visualization, and automated aberration detection. However, several constraints and challenges were encountered during the pilot implementation of ISS in rural China.
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| 8. |
- Zhao, Zeng-Ren, et al.
(författare)
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Nup88 mRNA overexpression in colorectal cancers and relationship with p53
- 2010
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Ingår i: CANCER BIOMARKERS. - : IOS Press. - 1574-0153. ; 8:2, s. 73-80
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We measured nucleoporin 88 (Nup88) mRNA expression in primary colorectal cancers to investigate its relationship with clinicopathological features and p53. Methods: The primary cancer tissues, adjacent noncancerous tissues and the proximal and distant margins of normal mucosa were collected from 73 colorectal cancer patients during surgery. Nup88 mRNA expression was measured on these fresh specimens and on colon cell lines HCT-116 (P53+/+) and HCT-116 (P53-/-) by RT-PCR while p53 mRNA and beta-actin as controls. Nup88 and p53 protein expression were then immunohistochemistrically examined in other 25 colorectal cancers specimens paraffin embedded and formalin fixed. Results: Nup88 expression was higher in primary cancer tissues than in adjacent noncancerous tissues, and in the proximal and distant margins of normal mucosa. Overexpression of Nup88 mRNA was statistically associated with TNM stage (P = 0.044), lymphatic metastasis (P = 0.022), and cancer location (P = 0.036), while not related to gender, age of patients and histological type, infiltration depth, and differentiation of cancers. The expression of Nup88 mRNA in the HCT-116 (P53-/-) cell line was not significantly different from expression in the HCT-116 (P53+/+) cell line. And there was no correlation between Nup88 and p53 protein expression (r = 0.632, P = 0.368). Conclusions: Nup88 mRNA was overexpressed in colorectal cancers and the overexpression was associated with cancer development and aggressiveness. Nup88 might be regard as essential contributor to nodal metastagenicity of colorectal cancer.
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| 9. |
- Zhao, Zeng-Ren, et al.
(författare)
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Significance of mRNA and Protein Expression of MAC30 in Progression of Colorectal Cancer
- 2011
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Ingår i: Chemotherapy. - Basel : Karger AG. - 0009-3157 .- 1421-9794. ; 57:5, s. 394-401
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Tidskriftsartikel (refereegranskat)abstract
- Background: Meningioma-associated protein (MAC30), first described to be overexpressed in meningiomas, exhibits altered expression in certain human tumors. The aim of our study was to investigate the expression of MAC30 mRNA and its correlation with clinicopathological variables in human colorectal cancer (CRC). Methods: MAC30 mRNA expression was first examined in 55 CRCs, along with the samples from the matched distant normal and adjacent noncancerous tissue by RT-PCR, further verified in 18 CRCs by quantitative RT-PCR. MAC30 protein expression was detected by Western blot in 10 CRCs, and DNA sequencing was performed in 1 case of the paired CRC and the matched noncancerous specimen. MAC30 mRNA expression in two colon cancer cell lines, HCT-116(p53-/-) and HCT-116(p53+/+), was detected by quantitative RT-PCR. Results: The mRNA expression of MAC30 was increased in CRC when compared with distant normal (p < 0.01) and adjacent noncancerous mucosa (p < 0.01). The mean value of MAC30 mRNA expression in the tumor located in the colon was higher than in the rectum (0.677 +/- 0.419 vs. 0.412 +/- 0.162, p = 0.005). As the tumor penetrated the wall of the colon/rectum, MAC30 mRNA expression notably increased in tumors with T3+T4 stage compared to tumors with T1+T2 stage (0.571 +/- 0.364 vs. 0.404 +/- 0.115, p = 0.014). MAC30 protein expression in CRCs was also remarkably elevated compared to the adjacent noncancerous mucosa. There was no mutation in the coding region of the MAC30 gene either in CRC or in the noncancerous mucosa. mRNA expression of p53 was notably decreased in HCT-116(p53-/-) compared to HCT-116(p53+/+), while MAC30 did not vary greatly. Conclusion: The overexpression of MAC30 might be involved in the development and aggressiveness of CRCs, especially in the colon.
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| 10. |
- Zou, Qi, et al.
(författare)
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A near-infrared "on-off" fluorescent and colourimetric cyanide chemodosimeter based on phenothiazine with applications in living cell imaging
- 2014
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 4:104, s. 59809-59816
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Tidskriftsartikel (refereegranskat)abstract
- A great deal of effort has been devoted to developing easy-to-use near-infrared probes for detecting analytes due to their advantages in the field of biosensing. Herein, a near-infrared "on-off" fluorescent chemodosimeter PTZ based on dicyano-vinyl-functionalised phenothiazine was designed and synthesised. The PTZ compound was shown to efficiently recognise cyanide ions in aqueous media by virtue of the special nucleophilicity of cyanide ions, which affects the intramolecular charge transfer efficiency in the molecule. Furthermore, it was found that it exhibited a rapid colourimetric and quenchable near-infrared (NIR) fluorescent response to cyanide ions with a detection limit as low as 67 nM, and that other anions showed almost no interference even at high concentrations. Optical spectroscopic measurements, H-1 NMR and mass spectrometry titrations, and theoretical simulations were carried out to elucidate the sensing mechanism of compound PTZ. Moreover, potential applications of this compound for biosensing have been exemplified by the successful fluorescent microscopic imaging for the detection of cyanide ions in HeLa cells.
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