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Purpose To evaluate the influence of refractive error and axial length (AL) on retinal vascular network geometry measurements in an adult Asian population. Methods This was a population‐based, cross‐sectional study on 2882 persons with diabetes in the Singapore Malay Eye Study (SiMES). Spherical equivalent refraction (SE) was assessed using an autokeratorefractometer and subjective refraction. AL was measured by IOL Master. Retinal vascular caliber, tortuosity, and branching characteristics were quantified from retinal fundus photographs using a semi‐automated computer‐assisted program according to a standardized protocol. Results In multivariate analyses adjusting for age, gender, education, smoking, blood pressure, diabetes status, and anti‐hypertensive medication use, longer AL and more myopic refraction were associated with narrower retinal arterioles and venules,(p ≤ 0.001 for all) and less tortuous (straighter) arterioles,(p < 0.001 for both). Longer AL and more myopic refraction were also associated with increased branching coefficients in both arterioles (p < 0.001 for both) and venules.(p = 0.02 and p < 0.001 respectively). Longer AL and more myopic refraction were associated with more acute branching angles in arterioles (p < 0.001 for both) but not venules. Conclusion Myopic refractive errors and longer AL are associated with narrower retinal arterioles and venules, less tortuous arterioles, and increased branching coefficients in both arterioles and venules. These findings provide insights into ocular blood flow in myopia, and also suggest that future studies evaluating these retinal parameters should account for the influence of AL and refractive error.

The mechanism of the self-assembly and fibrillization of the prion-like domains lies at the heart of their physiology and pathology. Here with the same methods previously established, we aimed to further decipher the mechanism by characterizing two prion-like sequences with the electrostatic properties very different from that of the full-length TDP-43 prion-like domain with a very basic pI value: namely the C-half of the TDP-43 prion-like domain only abundant in Gly, Ser, Asn and Gln with a pI of ~6.3, and the FUS prion-like domain enriched with Gly, Ser, Gln and Tyr with a pI of ~3.5. Interestingly, the C-half with the TDP-43 unique hydrophobic region removed is no longer able to form insoluble aggregates/fibrils but still capable of self-assembling into the reversible hydrogel with cross-β structures, despite being much slower than the fulllength. On the other hand, the FUS prion-like domain rapidly self-assembles into the reversible hydrogel with cross-β fibrillar structures in 1 mM phosphate buffer at pH 6.8 but its self-assembly becomes very slow in 50 mM MES buffer at pH 5. Biol 14:e1002338). This unambiguously indicates that the self-assembly of the prion-like domains is not generally governed by the electrostatic interaction. Rather, their self-assembly and fibrillization are specified by the sequences despite being highly polar and degenerative. Furthermore, our study provides the first evidence that the formation of reversible hydrogel with cross-β structures is separable from fibrillization of the prion-like domain. Finally, our results also successfully reconcile the previous discrepancy about the conformation and mechanism of the self-assembly of the FUS prion-like domain. Our study reveals that despite having completely different electrostatic properties, the full-length and C-half of the TDP-43 prion-like domain, as well as FUS prion-like domain all have the similar pH-dependence in self-assembly as we previously reported (Lim et al., [2016] PLOS

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Commonly used monolayer cancer cell cultures fail to provide a physiologically relevant environment in terms of oxygen delivery. Here, we describe a three-dimensional bioreactor system where cancer cells are grown in Matrigel in modified 6-well plates. Oxygen is delivered to the cultures through a polydimethylsiloxane (PDMS) membrane at the bottom of the wells, with microfabricated PDMS pillars to control oxygen delivery. The plates receive 3% oxygen from below and 0% oxygen at the top surface of the media, providing a gradient of 3% to 0% oxygen. We compared growth and transcriptional profiles for cancer cells grown in Matrigel in the bioreactor, 3D cultures grown in 21% oxygen, and cells grown in a standard hypoxia chamber at 3% oxygen. Additionally, we compared gene expression of conventional 2D monolayer culture and 3D Matrigel culture in 21% oxygen. We conclude that controlled oxygen delivery may provide a more physiologically relevant 3D system.

Purpose To determine the corneal biomechanical parameters measured with the Reichert Ocular Response Analyser(ORA) in Singaporean children, and to assess their correlations with refractive error and biometry Methods This was a cross sectional study of 271 subjects from the Singapore Cohort Study of Risk Factors for Myopia(SCORM). Corneal hysteresis (CH), corneal resistance factor(CRF), central corneal thickness(CCT) and intraocular pressure(IOPcc) were measured with the ORA. Spherical equivalent refraction, axial length, height, weight, and blood pressure were measured. Results The mean age of the study population was 13.97±0.89years, the gender distribution was almost equal(138 males,50.9%),and the majority were Chinese.The mean CH and CRF were 11.78±1.55mmHg and 11.81±1.71mmHg. CH and CRF did not vary with age, sex or race. CH and CRF did not vary with myopia (p=0.79;0.83), or axial length (r=‐0.11 and ‐0.05,p=0.08 and 0.40). Multivariate analyses were performed with CH, CRF or CCT as the dependent and age, gender, race, weight, IOPcc, CCT, SE refraction, and corneal curvature as covariates. CH was significantly associated with IOP (beta=‐0.22(95%CI ‐0.27,‐0.17)), CCT (beta=0.03(0.02,0.03)) and corneal curvature (beta=‐1.13(‐2.08,‐0.19)). CRF was significantly associated with IOP, CCT and corneal curvature.(beta=0.08(0.02,0.14);0.03(0.03,0.04) and ‐1.39(‐2.54,‐0.23) respectively). The only factor predictive of decreased CCT was Malay or Indian race compared with Chinese. Conclusion The CH and CRF values in our study on children are slightly higher than in adult studies. CH and CRF are not associated with refractive error or axial length. Flatter corneas are associated with lower CH and CRF readings