Variations in the proliferative activity of the peripheral retina correlate with postnatal ocular growth in squamate reptiles

Abstract The retina is a complex, multilayered tissue responsible for the perception of visual stimuli from the environment. Contrary to mammals, the capacity for postnatal eye growth in fish and amphibians, and to a lower extent in birds, is coordinated with a progenitor population residing in the ciliary marginal zone (CMZ) at the retinal peripheral margin. However, little is known about embryonic retinogenesis and postnatal retinal growth in squamates (lizards, snakes), despite their exceptional array of ecologies and ocular morphologies. Here we address this gap by performing the first large-scale study assessing both ontogenetic and adult changes in the stem/progenitor activity of the squamate peripheral retina. Our study reveals for the first time that squamates exhibit a source of proliferating progenitors persisting post embryogenesis in a newly identified retinociliary junction anteriorly adjacent to the retina. This region is strikingly similar to the vertebrate CMZ by its peripheral location and pseudostratified nature, and shares a common pattern of slow-cycling cells, spatial differentiation gradient, and response to postnatal ocular growth. Additionally, its proliferative activity varies considerably among squamate species, in correlation with embryonic and postnatal differences in eye size and growth. Together our data indicate that squamates possess a proliferative peripheral retina that acts as a source of progenitors to compensate, at least in part, for postnatal ocular growth. Our findings also highlight the remarkable variation in activity and location of vertebrate retinal progenitors, indicating that the currently accepted scenario of reduced CMZ activity over the course of evolution is too simplistic. This article is protected by copyright. All rights reserved.Peer reviewe

Effects of diet and exercise interventions on diabetes risk factors in adults without diabetes: meta-analyses of controlled trials

BACKGROUND AND AIMS: Fasting insulin (FI), fasting glucose (FG), systolic blood pressure (SBP), high density lipoproteins (HDL), triacylglycerides (TAG), and body mass index (BMI) are well-known risk factors for type 2 diabetes. Reliable estimates of lifestyle intervention effects on these factors allow diabetes risk to be predicted accurately. The present meta-analyses were conducted to quantitatively summarize effects of diet and exercise intervention programs on FI, FG, SBP, HDL, TAG and BMI in adults without diabetes. MATERIALS AND METHODS: MEDLINE and EMBASE were searched to find studies involving diet plus exercise interventions. Studies were required to use adults not diagnosed with type 2 diabetes, involve both dietary and exercise counseling, and include changes in diabetes risk factors as outcome measures. Data from 18, 24, 23, 30, 29 and 29 studies were used for the analyses of FI, FG, SBP, HDL, TAG and BMI, respectively. About 60% of the studies included exclusively overweight or obese adults. Mean age and BMI of participants at baseline were 48 years and 30.1 kg/m(2). Heterogeneity of intervention effects was first estimated using random-effect models and explained further with mixed-effects models. RESULTS: Adults receiving diet and exercise education for approximately one year experienced significant (P <0.001) reductions in FI (-2.56 ± 0.58 mU/L), FG (-0.18 ± 0.04 mmol/L), SBP (-2.77 ± 0.56 mm Hg), TAG (-0.258 ± 0.037 mmol/L) and BMI (-1.61 ± 0.13 kg/m(2)). These risk factor changes were related to a mean calorie intake reduction of 273 kcal/d, a mean total fat intake reduction of 6.3%, and 40 minutes of moderate intensity aerobic exercise four times a week. Lifestyle intervention did not have an impact on HDL. More than 99% of total variability in the intervention effects was due to heterogeneity. Variability in calorie and fat intake restrictions, exercise type and duration, length of the intervention period, and the presence or absence of glucose, insulin, or lipid abnormalities explained 23-63% of the heterogeneity. CONCLUSIONS: Calorie and total fat intake restrictions coupled with moderate intensity aerobic exercises significantly improved diabetes risk factors in healthy normoglycemic adults although normoglycemic adults with glucose, insulin, and lipid abnormalities appear to benefit more

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies

Effects of stacking sequence on the impact resistance in composite laminates--Part 2: Prediction Method

NRC publication: Ye

A Special Uniaxial Coupon Test Specimen for the Simulation of Multiple Site Fatigue Crack Growth and Link-up in Fuselage Skin Splices

NRC publication: Ye

Empirical Modeling of the Effect of Corrosion on Fatigue in Aircraft Lap Joints to Assist in Determining Cost Effective Maintenance - ABSTRACT ONLY

Peer reviewed: YesNRC publication: Ye

Impact Damage Resistance in Composite Structures

NRC publication: Ye

Conductive-Heat Transfer through Carbon Fibre/Epoxy Composite Tooling

Peer reviewed: YesNRC publication: Ye

Prediction of Impact-Induced Delamination in Composite Plates

NRC publication: Ye