Evidence for electron transfer between graphene and non‐covalently bound π‐systems

Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet‐chemical non‐covalent functionalization of graphene with cationic π‐systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF‐SIMS. The charged π‐systems show a p‐doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p‐doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping

AC and AG Dinucleotide Repeats in the PAX6 P1 Promoter are Associated with High Myopia

Purpose: The PAX6 gene, located at the reported myopia locus MYP7 on chromosome 11p13, was postulated to be associated with myopia development. This study investigated the association of PAX6 with high myopia in 379 high myopia patients and 349 controls. Methods: High myopia patients had refractive errors of –6.00 diopters or greater and axial length longer than 26 mm. Control subjects had refractive errors less than –1.00 diopter and axial length shorter than 24 mm. The P1 promoter, all coding sequences, and adjacent splice-site regions of the PAX6 gene were screened in all study subjects by polymerase chain reaction and direct sequencing. PAX6 P1 promoter-luciferase constructs with variable AC and AG repeat lengths were prepared and transfected into human ARPE-19 cells prior to assaying for their transcriptional activities. Results: No sequence alterations in the coding or splicing regions showed an association with high myopia. Two dinucleotide repeats, (AC)m and (AG)n, in the P1 promoter region were found to be highly polymorphic and significantly associated with high myopia. Higher repeat numbers were observed in high myopia patients for both (AC)m (empirical p = 0.013) and (AG)n (empirical p = 0.012) dinucleotide polymorphisms, with a 1.327-fold increased risk associated with the (AG)n repeat (empirical p = 0.016; 95% confidence interval: 1.059–1.663). Luciferase-reporter analysis showed elevated transcription activity with increasing individual (AC)m and (AG)n and combined (AC)m(AG)n repeat lengths. Conclusions: Our results revealed an association between high myopia and AC and AG dinucleotide repeat lengths in the PAX6 P1 promoter, indicating the involvement of PAX6 in the pathogenesis of high myopia

Multiple Gene Polymorphisms in the Complement Factor H Gene Are Associated with Exudative Age-Related Macular Degeneration in Chinese

PURPOSE. Variants in the complement factor H (CFH) gene have been shown to be strongly associated with age-related macular degeneration (AMD). In this study, sequence alterations in CFH were investigated in 163 Chinese patients with exudative AMD and 155 unrelated Chinese control subjects. METHODS. All the 22 CFH exons, intron-exon boundaries, and promoter sequences were screened by polymerase chain reaction and DNA sequencing. RESULTS. Fifty-eight sequence changes, 42 of them novel, were identified. Six SNPs with an allele frequency Ͼ30% were significantly associated with exudative AMD. SNP rs3753396 was novel; the rest had been reported: rs3753394, rs551397, rs800292, rs2274700, and rs1329428. Two haplotype blocks were constructed. The TG haplotype for rs551397 and rs800292 was the major haplotype that conferred a significantly increased susceptibility to exudative AMD (P corr ϭ 0.0001, OR ϭ 1.91, 95% CI ϭ 1.36 -2.68). CONCLUSIONS. The findings support prior evidence that the CFH gene is one of the AMD-associated genes. There is a different distribution pattern of CFH variants in the Chinese compared with other populations. Individual SNP and haplotype analyses revealed that the ancient alleles at the 5Ј end of CFH contribute to an increased susceptibility to exudative AMD. (Invest Ophthalmol Vis Sci. 2008;49:3312-3317) DOI:10.1167/iovs.07-1517 A ge-related macular degeneration (AMD; MIM 603075; Mendelian Inheritance in Man) is a major cause of irreversible visual impairment and blindness in people older than 65 years in developed countries. 1,2 The occurrence of AMD is pan ethnic, and a high prevalence AMD has been reported in the elderly Chinese population. 5 Therefore, a greater understanding of the primary pathophysiology is needed to advance treatment and preventive measures. The etiology of AMD is complex and multifactorial, probably resulting from interactions between environmental and multigenetic factors. 6 Genetic association studies have revealed that single nucleotide polymorphisms (SNPs) in the complement factor H gene (CFH; MIM 134370; e.g., Tyr402His) are significantly associated with susceptibility to AMD. 25 A fine-scale linkage disequilibrium mapping of AMD in the CFH region detected a point location of a causal variant between exons 1 and 2 of CFH other than exon 9 for Tyr402His. MATERIALS AND METHODS Patients and Control Subjects 21 Also recruited and given complete ophthalmic examinations were 155 unrelated control subjects, 72 men and 83 women ranging in age at recruitment from 60 to 99 years (mean Ϯ SD, 73.1 Ϯ 6.5 years). They matched the patients by age and gender and had no sign of AMD or other eye diseases, except mild myopia or senile cataract. The study protocol was approved by the Ethics Committee on Human Research, the Chinese University of Hong Kong. All the procedures used conformed to the tenets of the Declaration of Helsinki. Informed consent was obtained from all study subjects after explanation of the nature of the study. Sample Collection, PCR Amplification, DNA Sequencing, and SNP Genotyping Venous blood was obtained from each study subject, and genomic DNA was extracted with a DNA blood kit (QIAamp; Qiagen, Hilden, Germany). The promoter sequence up to Ϫ867 upstream and all coding sequences of the CFH gene, including intron-exon boundaries, were screened for sequence alterations. Primers were generated based on the GenBank sequence of CFH (NM_000186.2; http://www.ncbi. nlm.nih.gov/Genbank; provided in the public domain by the National Center for Biotechnology Information, Bethesda, MD). PCR was performed on a thermal cycler (model 9700; Applied Biosystems, Inc. [ABI], Foster City, CA) with optimized protocols 27 Statistical Analysis Hardy-Weinberg equilibrium (HWE) for each polymorphism was tested by 2 test. Allele or genotype frequencies between cases and control subjects were compared by 2 analysis or the Fisher exact test. The odds ratios (ORs) of the alleles and haplotypes were estimated by 2 test (SPSS ver.15.0; SPSS Inc., Chicago, IL). Population attributable risk (PAR) of the risk genotype was calculated with the formula f(R Ϫ 1)/R, where f is the faction of cases with the risk genotype and R is the measure of OR 8 . A pair-wise linkage disequilibrium (LD, DЈ) estimation between polymorphisms with a minor allele frequency (MAF) Ͼ 1%, and EM-based haplotype association analysis were performed with Haploview (ver. 3.32, from http://www.broad.mit.edu/mpg/ haploview/ provided in the public domain by the Broad Institute, Massachusetts Institute of Technology, Cambridge, MA). For multiple comparison, probabilities were corrected by permutation test (iterations, 10,000). Statistical significance was defined as a corrected P (P corr ) Ͻ 0.05. RESULTS CFH Variants in the Study Subjects A total of 58 sequence variations were identified, all of which followed Hardy Weinberg Equilibrium Six of the seven common variants Six SNPs were identified in the promoter, all supported decreased susceptibility to AMD Haplotype Association Analysis LD analysis revealed extension of LD throughout the CFH gene. We included SNPs with MAF Ͼ 5% and two missense changes, rs1061170 (Tyr402His) and Val837Ile, in our haplotype association analysis. Two distinct haplotype blocks were detected The haplotypes H3 and H4, which were defined by all six AMD-associated SNPs, conferred significantly reduced or increased AMD susceptibility (H3: OR ϭ 0.56, 95% CI ϭ 0.39 -0.80; H4: OR ϭ 1.63, 95% CI ϭ 1.19 -2.23). When a G allele of rs1065489 (Asp936Glu) was included in these two haplotypes, the H5, which contained all the alleles in H3, remain significantly associated with the disease (P corr ϭ 0.0012). However, when a G allele or a T allele was added to the H4, the newly constructed H6 and H7 were no longer AMD associated (P corr ϭ 0.052 and 0.177, respectively). We constructed two-allele haplotypes by using rs800292 (Val62Ile) with the uncommon SNPs rs1061170 (Tyr402His) and Val837Ile, to investigate the effects of the minor variants. H10 and H11, containing a T allele of rs1061170 (Tyr402His), remained significantly associated with AMD. However, the haplotypes containing a C allele of rs1061170 DISCUSSION Although the pathogenesis of exudative AMD has not been definitively elucidated, studies in the past few years have revealed important information on its genetic basis. Polymorphisms in the CFH gene have been shown to be AMD associated in different ethnic groups, although there are obvious differences in the occurrence of disease-susceptible SNPs between Caucasian and Oriental populations. 26 mapped a point location for a causal variant between exons 1 and 2, which approximates block 1 in our present study, suggesting that the 5Ј region of the CFH (N-terminal of factor H) is commonly associated with AMD in both Chinese and Caucasians. We found haplotype block 2 spanning a region from exon 10 to intron 15 and containing SNP rs2274700 (Ala473Ala, exon 10), which have recently been shown to have a strong association with AMD in Caucasians and Japanese. Besides the haplotypes in the two haplotype blocks, the haplotypes defined by the six common SNPs (H3, H4) were also significantly associated with exudative AMD. However, when Asp936Glu (in exon 18) was included in the at-risk haplotype H4 for association analysis, the haplotypes H6 and H7, including a G or a T allele respectively, were no longer significantly associated with the disease (P corr Ͼ 0.05). Thus, Asp936Glu is less likely to be a risk factor for exudative AMD in Chinese individuals, indicating the C-terminal of the factor H contributes less than other parts of the polypeptide to the development of exudative AMD. This observation is consistent with the findings of Hageman et al

Manganese Superoxide Dismutase and Chemokine Genes Polymorphisms in Chinese Patients with Anterior Uveitis

PURPOSE. To investigate the association of single-nucleotide polymorphisms (SNPs) in the manganese superoxide dismutase (MnSOD) and two chemokine genes (CCL2 and CCL5) in patients with anterior uveitis (AU). METHODS. Seventy-nine Chinese patients with acute AU were recruited, and genotyping of four SNPs including MnSOD 47, CCL2 Ϫ2518, CCL2 Ϫ2076, and CCL5 Ϫ403 alleles was performed with SNP genotyping assays. The genotype and allele frequencies were compared between patients with AU and 206 healthy control subjects. Analyses were also stratified according to the HLA-B27 status of the patients. RESULTS. There were significant increases in the frequency of the AA homozygosity in the MnSOD 47 SNP (P ϭ 0.049) and in the CCL2 Ϫ2518G allele frequency and GG homozygosity in patients with AU compared with control subjects (P ϭ 0.017 and P ϭ 0.024, respectively). No significant association was found between AU with the CCL2 Ϫ2076 and CCL5 Ϫ403 SNPs. Subgroup analyses showed that the MnSOD 47A polymorphism was significantly associated with AU in HLA-B27-positive patients, but not in HLA-B27-negative patients, whereas the CCL2 Ϫ2518G polymorphism was significantly associated with AU in HLA-B27-negative patients, but not in HLA-B27-positive patients. CONCLUSIONS. The 47A polymorphism in the MnSOD gene and the Ϫ2518G polymorphism in the CCL2 gene are associated with the development of AU in HLA-B27-positive and -negative Chinese patients, respectively. Further studies to evaluate the interactions of the HLA-B27 status and these SNPs are warranted. (Invest Ophthalmol Vis Sci

Towards a global partnership model in interprofessional education for cross-sector problem-solving

Objectives A partnership model in interprofessional education (IPE) is important in promoting a sense of global citizenship while preparing students for cross-sector problem-solving. However, the literature remains scant in providing useful guidance for the development of an IPE programme co-implemented by external partners. In this pioneering study, we describe the processes of forging global partnerships in co-implementing IPE and evaluate the programme in light of the preliminary data available. Methods This study is generally quantitative. We collected data from a total of 747 health and social care students from four higher education institutions. We utilized a descriptive narrative format and a quantitative design to present our experiences of running IPE with external partners and performed independent t-tests and analysis of variance to examine pretest and posttest mean differences in students’ data. Results We identified factors in establishing a cross-institutional IPE programme. These factors include complementarity of expertise, mutual benefits, internet connectivity, interactivity of design, and time difference. We found significant pretest–posttest differences in students’ readiness for interprofessional learning (teamwork and collaboration, positive professional identity, roles, and responsibilities). We also found a significant decrease in students’ social interaction anxiety after the IPE simulation. Conclusions The narrative of our experiences described in this manuscript could be considered by higher education institutions seeking to forge meaningful external partnerships in their effort to establish interprofessional global health education