Dynamic Studies of Scaffold-dependent Mating Pathway in Yeast

The mating pathway in \emph{Saccharomyces cerevisiae} is one of the best understood signal transduction pathways in eukaryotes. It transmits the mating signal from plasma membrane into the nucleus through the G-protein coupled receptor and the mitogen-activated protein kinase (MAPK) cascade. According to the current understandings of the mating pathway, we construct a system of ordinary differential equations to describe the process. Our model is consistent with a wide range of experiments, indicating that it captures some main characteristics of the signal transduction along the pathway. Investigation with the model reveals that the shuttling of the scaffold protein and the dephosphorylation of kinases involved in the MAPK cascade cooperate to regulate the response upon pheromone induction and to help preserving the fidelity of the mating signaling. We explored factors affecting the dose-response curves of this pathway and found that both negative feedback and concentrations of the proteins involved in the MAPK cascade play crucial role. Contrary to some other MAPK systems where signaling sensitivity is being amplified successively along the cascade, here the mating signal is transmitted through the cascade in an almost linear fashion.Comment: 36 pages, 9 figure

Medium-Term Visual Outcomes of Apodized Diffractive Multifocal Intraocular Lens with +3.00 D Addition Power

Purpose. To evaluate 2-year visual acuities and questionnaire after bilateral implantation of SN6AD1 multifocal intraocular lens (MIOL) or SN60WF IOL. Methods. Patients randomly scheduled for bilateral implantation of SN6AD1 MIOL and SN60WF IOL with 2-year follow-up were enrolled. Uncorrected/corrected distance and near visual acuity, uncorrected intermediate visual acuity at 63 cm under high and low contrast, reading activity, the defocus curve, and a quality-of-life questionnaire were evaluated. Results. Each group comprised 20 patients. Uncorrected intermediate visual acuities and uncorrected near visual acuity were better in SN6AD1 group than in SN60WF group (P = 0.005, P = 0.011, and P < 0.001). In SN6AD1 group, the uncorrected intermediate and near visual acuities 1 year and 2 years postoperatively were reduced than postoperative 3-month outcomes, respectively. SN6AD1 group reported superior overall spectacle independence and inferior satisfaction. SN6AD1 group had a longer reading newspaper duration than SN60WF group (P = 0.036). When using mobile phone, SN6AD1 group had a more comfortable distance than SN60WF group (P < 0.001) and higher speed of reading fixed text message (P < 0.001). Conclusion. SN6AD1 MIOL provided a satisfactory full range of visual acuities and questionnaire performance 2 years postoperatively. One-year and 2-year uncorrected near and intermediate visual acuities of SN6AD1 MIOL were lower than those 3 months postoperatively

Time trends and heterogeneity in the disease burden of visual impairment due to cataract, 1990–2019: A global analysis

ObjectivesThis study aimed to estimate the disease burden of cataract and evaluate the contributions of risk factors to cataract-associated disability-adjusted life years (DALYs).Materials and methodsPrevalence and DALYs of visual impairment due to cataract were extracted from the Global Burden of Disease (GBD) study 2019 to explore time trends and annual changes. Regional and country-level socioeconomic indexes were obtained from open databases. The time trend of prevalence and DALYs was demonstrated. Stepwise multiple linear regression was used to evaluate associations between the age-standardized rate of DALYs of cataract and potential predictors.ResultsGlobal Prevalence rate of visual impairment due to cataract rose by 58.45% to 1,253.9 per 100,000 population (95% CI: 1,103.3 to 1,417.7 per 100,000 population) in 2019 and the DALYs rate rose by 32.18% from 65.3 per 100,000 population (95% CI: 46.4 to 88.2 per 100,000 population) in 1990 to 86.3 per 100,000 population (95% CI: 61.5 to 116.4 per 100,000 population) in 2019. Stepwise multiple linear regression model showed that higher refractive error prevalence (β = 0.036, 95% CI: 0.022, 0.050, P &lt; 0.001), lower number of physicians per 10,000 population (β = −0.959, 95% CI: −1.685, −0.233, P = 0.010), and lower level of HDI (β = −134.93, 95% CI: −209.84, −60.02, P = 0.001) were associated with a higher disease burden of cataract.ConclusionSubstantial increases in the prevalence of visual impairment and DALYs of cataract were observed from 1990 to 2019. Successful global initiatives targeting improving cataract surgical rate and quality, especially in regions with lower socioeconomic status, is a prerequisite to combating this growing burden of cataract in the aging society

Biomechanical Measurement of Rabbit Cornea by a Modified Scheimpflug Device

Purpose. To explore the probability and variation in biomechanical measurements of rabbit cornea by a modified Scheimpflug device. Methods. A modified Scheimpflug device was developed by imaging anterior segment of the model imitating the intact eye at various posterior pressures. The eight isolated rabbit corneas were mounted on the Barron artificial chamber and images of the anterior segment were taken at posterior pressures of 15, 30, 45, 60, and 75 mmHg by the device. The repeatability and reliability of the parameters including CCT, ACD, ACV, and CV were evaluated at each posterior pressure. All the variations of the parameters at the different posterior pressures were calculated. Results. All parameters showed good intraobserver reliability (Cronbach’s alpha; intraclass correlation coefficient, α, ICC > 0.96) and repeatability in the modified Scheimpflug device. With the increase of posterior pressures, the ratio of CCT decreased linearly and the bulk modulus gradually reduced to a platform. The increase of ACD was almost linear with the posterior pressures elevated. Conclusions. The modified Scheimpflug device was a valuable tool to investigate the biomechanics of the cornea. The posterior pressure 15–75 mmHg range produced small viscoelastic deformations and nearly linear pressure-deformation response in the rabbit cornea

The burden, causes, and determinants of blindness and vision impairment in Asia: An analysis of the Global Burden of Disease Study

Asia accounts for more than half of the world's population and carries a substantial proportion of the global burden of blindness and vision impairment. Characterising this burden, as well as its causes and determinants, could help with devising targeted interventions for reducing the occurrence of blindness and visual impairment. Using the Global Burden of Disease Study 2019 database, we retrieved data on the number of disability-adjusted life years (DALYs); crude and age-standardised rates; and the prevalence (with 95% uncertainty intervals (95%UIs)) of blindness and vision loss due to six causes (age-related macular degeneration, cataracts, glaucoma, near-vision impairment, refractive error, and other vision loss) for Asian countries for the period between 1990 and 2019. We defined DALYs as the sum of the years lost due to disability and years of life lost, and calculated age-standardised figures for the number of DALYs and prevalence by adjusting for population size and age structure. We then evaluated the time trend of the disease burden and conducted subgroup analyses by gender, age, geographic locations, and socio-demographic index (SDI). In 2019, the DALYs and prevalence of blindness and vision loss had risen by 90.1% and 116% compared with 1990, reaching 15.84 million DALYs (95% UI = 15.83, 15.85) and 506.71 million cases (95% UI = 506.68, 506.74). Meanwhile, the age-standardised rate of DALYs decreased from 1990 to 2019. Cataracts, refractive error, and near vision impairment were the three most common causes. South Asia had the heaviest regional disease burden (age-standardised rate of DALYs = 517 per 100 000 population; 95% UI = 512, 521). Moreover, the burden due to cataracts ranked high in most Asian populations. Being a woman; being older; and having a lower national SDI were factors associated with a greater vision loss burden. The burden due to vision loss remains high in Asian populations. Cataracts, refractive error, and near vision loss were the primary causes of blindness and vision loss. Greater investment in ocular disease prevention and care by countries with lower socioeconomic status is needed, as well as specific strategies targeting cataract management, women and the elderly

Expression of Cytokines, Chmokines and Growth Factors in Patients Undergoing Cataract Surgery with Femtosecond Laser Pretreatment.

To describe cytokines, chemokines and growth factors profiles in patients undergoing cataract surgery with femtosecond laser pretreatment and investigate their relationships with the postoperative in vivo inflammation index.Aqueous humor was collected from 22 eyes after femtosecond laser pretreatment and from 22 eyes at the beginning of routine cataract surgery. The levels of 45 inflammation-related mediators were measured using multiplex fluorescent bead-based immunoassays. Laser flare photometry was measured preoperatively and at 1 day, 7 days and 30 days postoperatively.Compared with the control group, the femtosecond laser treatment group showed significantly higher aqueous humor levels of fibroblast growth factor (FGF-2), tumor necrosis factor (TNF)-α, leukemia inhibitor factor (LIF), interleukin (IL)-1ra and IL-18, and significantly lower aqueous humor levels of IL-9, platelet-derived growth factor (PDGF)-BB, eotaxin and TNF-β. Postoperative aqueous flare was significantly greater in the manual cataract surgery group at 1 day (p<0.001), 7 days (p<0.001) and 30 days (p = 0.002).No correlation was found between the analyzed mediators and the aqueous flare values.The expression profiles of cytokines, chemokines and growth factors and the correlations of these profiles with the in vivo inflammatory indexes for patients undergoing cataract surgery with femtosecond laser pretreatment were identified. Our data indicate a disturbance of postoperative inflammation response after femtosecond laser treatment

Factors affecting the intelligibility of high-intensity-level-based speech

The present work examined factors affecting the intelligibility of high-intensity-level-based speech. Mandarin sentences were processed to contain only high-intensity segments confined by a 5-dB selected intensity range (SIR), with other segments replaced by noise. The processed stimuli were presented to normal-hearing listeners to recognize. The greatest intensity density occurred in the SIR with an upper boundary 3 dB below the peak intensity level, and this SIR yielded the highest intelligibility score in quiet. The SIR with the upper boundary at the peak intensity level yielded better intelligibility performance under noisy conditions, due largely to the relatively high effective signal-to-noise ratio

Time trends, associations and prevalence of blindness and vision loss due to glaucoma: an analysis of observational data from the Global Burden of Disease Study 2017

OBJECTIVE: To estimate global prevalence of blindness and vision loss caused by glaucoma, and to evaluate the impact of socioeconomic factors on it. DESIGN: A population-based observational study. SETTING: The prevalence of blindness and vision loss due to glaucoma were obtained from the Global Burden of Disease Study 2017 database. The Human Development Index (HDI), inequality-adjusted HDI and other socioeconomic data were acquired from international open databases. MAIN OUTCOME MEASURES: The prevalence of blindness and vision loss due to glaucoma by age, gender, subregion and Socio-Demographic Index (SDI) levels. Multiple linear regression analysis was performed to explore the associations between the prevalence and socioeconomic indicators. RESULTS: The overall age-standardised prevalence of blindness and vision loss due to glaucoma worldwide was 81.5 per 100 000 in 1990 and 75.6 per 100 000 in 2017. In 2017, men had a higher age-standardised prevalence than women (6.07% vs 5.42%), and the worldwide prevalence increased with age, from 0.5 per 100 000 in the 45–49 year age group to 112.9 per 100 000 among those 70+. Eastern Mediterranean and African regions had the highest prevalence during the whole period, while the Americas region had the lowest prevalence. The prevalence was highest in low-SDI and low-income regions while lowest in high-SDI and high-income regions over the past 27 years. Multiple linear regression showed cataract surgery rate (β=−0.01, p=0.009), refractive error prevalence (β=−0.03, p=0.024) and expected years of schooling (β= -8.33, p=0.035) were associated with lower prevalence, while gross national income per capita (β=0.002, p<0.001) was associated with higher prevalence. CONCLUSIONS: Lower socioeconomic levels and worse access to eyecare services are associated with higher prevalence of glaucoma-related blindness and vision loss. These findings provide evidence for policy-makers that investments in these areas may reduce the burden of the leading cause of irreversible blindness