Assessment of biosafety and implantation feasibility of novel phakic refractive lens.

PURPOSE: We investigated the biosafety and implantation feasibility of a new phakic refractive lens (PRL) in rabbit eyes. METHODS: Short PRLs (S-PRLs), large PRLs (L-PRLs), and large-grooved PRLs (LG-PRLs), were prepared by molding medical-grade liquid silicon. The cytotoxicity and cellular adhesion of the PRLs was assessed in vitro. To assess implantation feasibility, the S-PRL, L-PRL, and LG-PRL were implanted in the posterior chamber of rabbit eyes and the relative position was assessed by optical coherence tomography. The intraocular pressures (IOP) were compared between the S-PRL, L-PRL, LG-PRL, and control groups to evaluate the PRL biosafety after implantation. RESULTS: The in vitro assays showed that cell viability and cellular adhesion in the S-PRL, L-PRL and LG-PRL groups was not significantly different to those in the control group throughout the study. After implantation into the posterior chamber of rabbit eyes, there were no obvious signs of inflammation or increases in IOP at each time point relative to the control group, demonstrating good biosafety of the PRL. The relative positions of the L-PRLs and LG-PRLs in the posterior chamber were appropriate and the retention frequencies were high. CONCLUSIONS: The newly developed LG-PRL showed good biosafety with negligible in vitro cytotoxicity, ocular inflammation, or fluctuations in IOP. The LG-PRL provided the best implantation feasibility. The grooves on the LG-PRL provided channels for aqueous humor circulation. The LG-PRL is a promising type of PRL with an appropriate size and surface structure for effective correction of refractive errors in rabbit eyes.

Overexpression of MdARD4 Accelerates Fruit Ripening and Increases Cold Hardiness in Tomato.

Ethylene plays an important role in stress adaptation and fruit ripening. Acireductone dioxygenase (ARD) is pivotal for ethylene biosynthesis. However, the response of ARD to fruit ripening or cold stress is still unclear. In this study, we identified three members of Malus ARD family, and expression profile analysis revealed that the transcript level of MdARD4 was induced during apple fruit ripening and after apple plants were being treated with cold stress. To investigate its function in cold tolerance and fruit ripening, MdARD4 was ectopically expressed in Solanum lycopersicum cultivar 'Micro-Tom', which has been considered as an excellent model plant for the study of fruit ripening. At the cellular level, the MdARD protein expressed throughout Nicotiana benthamiana epidermal cells. Overexpression of MdARD4 in tomato demonstrated that MdARD4 regulates the ethylene and carotenoid signaling pathway, increases ethylene and carotenoid concentrations, and accelerates fruit ripening. Furthermore, MdARD4 increased the antioxidative ability and cold hardiness in tomato. To conclude, MdARD4 may potentially be used in apple breeding to accelerate fruit ripening and increase cold hardiness.

Genome-wide association analysis with gray matter volume as a quantitative phenotype in first-episode treatment-naïve patients with schizophrenia.

Reduced Gray matter (GM) volume is a core feature of schizophrenia. Mapping genes that is associated with the heritable disease-related phenotypes may be conducive to elucidate the pathogenesis of schizophrenia. This study aims to identify the common genetic variants that underlie the deficits of GM volume in schizophrenia. High-resolution T1 images and whole genome genotyping data were obtained from 74 first-episode treatment-naïve patients with schizophrenia and 51 healthy controls in the Mental Health Centre of the West China Hospital, Sichuan University. All participants were scanned using a 3T MR imaging system and were genotyped using the HumanHap660 Bead Array. Reduced GM volumes in three brain areas including right hOC3v in the collateral sulcus of visual cortex (hOC3vR), left cerebellar vermis lobule 10 (vermisL10) and right cerebellar vermis lobule 10 (vermisR10) were found in patients with schizophrenia [corrected].There was a group by genotype interaction when genotypes from genome-wide scan were subsequently considered in the case-control analyses. SNPs from three genes or chromosomal regions (TBXAS1, PIK3C2G and HS3ST5) were identified to predict the changes of GM volume in hOC3vL, vermisL10 and vermisR10. These results also highlighted the usefulness of endophenotype in exploring the pathogenesis of neuropsychiatric diseases such as schizophrenia although further independent replication studies are needed in the future.

Cortical surface area correlates with STON2 gene Ser307Pro polymorphism in first-episode treatment-naïve patients with schizophrenia.

BACKGROUND: Evidence shows that STON2 gene is associated with synaptic function and schizophrenia. This study aims to explore the relationship between two functional polymorphisms (Ser307Pro and Ala851Ser) of STON2 gene and the cortical surface area in first-episode treatment-naïve patients with schizophrenia and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Magnetic resonance imaging of the whole cortical surface area, which was computed by an automated surface-based technique (FreeSurfer), was obtained from 74 first-episode treatment-naïve patients with schizophrenia and 55 healthy controls. Multiple regression analysis was performed to investigate the effect of genotype subgroups on the cortical surface area. A significant genotype-by-diagnosis effect on the cortical surface area was observed. Pro-allele carriers of Ser307Pro polymorphism had larger right inferior temporal surface area than Ser/Ser carriers in the patients with schizophrenia; however, no significant difference was found in the same area in the healthy controls. The Ala851Ser polymorphism of STON2 gene was not significantly associated with the cortical surface area in patients with schizophrenia and healthy controls. CONCLUSIONS/SIGNIFICANCE: The present study demonstrated that the functional variant of the STON2 gene could alter cortical surface area on the right inferior temporal and contribute to the pathogenesis of schizophrenia.

[Association study of NOS1 gene polymorphisms and schizophrenia].

OBJECTIVE: To assess the association between nitric oxide synthase 1 (NOS1) gene polymorphisms and schizophrenia. METHODS: Twenty eight tag single nucleotide polymorphisms (SNPs) of NOS1 in 382 schizophrenic patients and 448 healthy individuals sampled from Chinese Han population were analyzed by a Illumina GoldenGate Genotyping Assay. RESULTS: One SNP (rs1520811) was found to be associated with schizophrenia, which however becomes negative after Bonferroni correction (P>0.05). Further analysis has failed to identify any association between particular haplotypes and the disease. CONCLUSION: Our results did not support a significant association between NOS1 gene polymorphisms and schizophrenia.

Association of APC and REEP5 gene polymorphisms with major depression disorder and treatment response to antidepressants in a Han Chinese population.

OBJECTIVE: Despite the high prevalence of depression and its considerable impact on the population, knowledge about the pathogenesis of the illness and the antidepressant treatment response is still unknown. METHODS: A total of 397 patients with major depression disorder (MDD) and 473 normal controls were employed in the present research. Twelve single nucleotide polymorphisms (SNPs) within the adenomatous polyposis coli (APC) and receptor accessory protein (REEP5) genes were selected for genotyping using the GoldenGate genotyping assay. A total of 165 MDD patients completed a 6-week antidepressant treatment. Responders were defined as patients with at least a 50% reduction in Hamilton Rating Scale for Depression total scores posttreatment. RESULTS: Two SNPs (rs2464805 and rs563556) within the APC gene exhibited a statistically significant association with MDD when analyzed by genotype and allele frequencies. Three SNPs (rs495794, rs153549 and rs153560) in the REEP5 gene showed significant statistical differences between the responders and nonresponders. CONCLUSIONS: The APC gene may be one of the susceptibility genes for MDD as well as a genetic link between psychiatric disease and cancer. REEP5 gene polymorphisms may influence antidepressant treatment response in MDD.

[Genome-wide association study with memory measures as a quantitative trait locus for schizophrenia].

OBJECTIVE: To assess the association between gene polymorphisms and memory function through a genome-wide association study (GWAS) of schizophrenia and control group. Memory cognition was used as a quantitative trait (QT). METHODS: Ninty-eight subjects with chronic schizophrenia and 60 matched controls were genotyped with HumanHap660 Bead Array. The results were correlated with quantitative traits including memory and memory delay. RESULTS: Five candidate genes, including RASGRF2 (rs401758, P = 8.03×10(-5)), PLCG2 (rs7185362, P= 4.54×10(-5)), LMO1 (rs484161, P=9.80×10(-7), CSMD1 (rs2469383, P= 2.77×10(-6)) and PRKG1 (rs7898516, P=6.94×10(-5)) were associated with memory cognition deficits. CONCLUSION: Using memory cognition as a quantitative trait, this Genome- wide association study has identified 5 susceptibility loci. With their association with nervous system development, neuronal growth, axon guidance and plasticity, brain development, above loci may play a role in the development of memory dysfunction in schizophrenia.