Changes in monkey crystalline lens spherical aberration during simulated accommodation in a lens stretcher

8 págs.; 7 figs.; 2 apps.© 2015 The Association for Research in Vision and Ophthalmology, Inc. PURPOSE. The purpose of this study was to quantify accommodation-induced changes in the spherical aberration of cynomolgus monkey lenses. METHODS. Twenty-four lenses from 20 cynomolgus monkeys (Macaca fascicularis; 4.4-16.0 years of age; postmortem time 13.5±13.0 hours) were mounted in a lens stretcher. Lens spherical aberration was measured in the unstretched (accommodated) and stretched (relaxed) states with a laser ray tracing system that delivered 51 equally spaced parallel rays along 1 meridian of the lens over the central 6-mm optical zone. A camera mounted below the lens was used to measure the ray height at multiple positions along the optical axis. For each entrance ray, the change in ray height with axial position was fitted with a third-order polynomial. The effective paraxial focal length and Zernike spherical aberration coefficients corresponding to a 6-mm pupil diameter were extracted from the fitted values. RESULTS. The unstretched lens power decreased with age from 59.3±6 4.0 diopters (D) for young lenses to 45.7±6 3.1 D for older lenses. The unstretched lens shifted toward less negative spherical aberration with age, from -6.3±0.7 lm for young lenses to-5.0±0.5 lm for older lenses. The power and spherical aberration of lenses in the stretched state were independent of age, with values of 33.5±6 3.4 D and-2.6±0.5 lm, respectively. CONCLUSIONS. Spherical aberration is negative in cynomolgus monkey lenses and becomes more negative with accommodation. These results are in good agreement with the predicted values using computational ray tracing in a lens model with a reconstructed gradient refractive index. The spherical aberration of the unstretched lens becomes less negative with age.Supported by National Institutes of Health Grants R01EY14225, R01EY021834, and F31EY021444 Ruth L. Kirschstein National Research Service Award individual predoctoral fellowship [BM]), and center Grant P30EY14801; Australian government Cooperative Research Centre Scheme (Vision CRC); Florida Lions Eye Bank; Karl R. Olsen and Martha E. Hildebrandt; an unrestricted grant from Research to Prevent Blindness; Henri and Flore Lesieur Foundation (JMP); Spanish government Grant FIS2011-25637; and European Research Council Grants ERC-2011-AdG-294099 and CSIC i-LINKþ0609Peer Reviewe

Human rights and community work. Complementary theories and practices

Much effort has been placed on developing international understandings of human rights without the corresponding attention to responsibilities. The authors argue that a community development framework may be useful in re-conceiving human rights in a more holistic way, and that social workers and community development workers are well placed to be 'grass roots human rights workers

Identification of Novel Antimalarial Chemotypes via Chemoinformatic Compound Selection Methods for a High-Throughput Screening Program against the Novel Malarial Target, PfNDH2: Increasing Hit Rate via Virtual Screening Methods

Malaria is responsible for approximately 1 million deaths annually; thus, continued efforts to discover new antimalarials are required. A HTS screen was established to identify novel inhibitors of the parasite's mitochondrial enzyme NADH:quinone oxidoreductase (PfNDH2). On the basis of only one known inhibitor of this enzyme, the challenge was to discover novel inhibitors of PfNDH2 with diverse chemical scaffolds. To this end, using a range of ligand-based chemoinformatics methods, ~17000 compounds were selected from a commercial library of ~750000 compounds. Forty-eight compounds were identified with PfNDH2 enzyme inhibition IC(50) values ranging from 100 nM to 40 μM and also displayed exciting whole cell antimalarial activity. These novel inhibitors were identified through sampling 16% of the available chemical space, while only screening 2% of the library. This study confirms the added value of using multiple ligand-based chemoinformatic approaches and has successfully identified novel distinct chemotypes primed for development as new agents against malaria

CD4CD8αα Lymphocytes, A Novel Human Regulatory T Cell Subset Induced by Colonic Bacteria and Deficient in Patients with Inflammatory Bowel Disease

It has become evident that bacteria in our gut affect health and disease, but less is known about how they do this. Recent studies in mice showed that gut Clostridium bacteria and their metabolites can activate regulatory T cells (Treg) that in turn mediate tolerance to signals that would ordinarily cause inflammation. In this study we identify a subset of human T lymphocytes, designated CD4CD8αα T cells that are present in the surface lining of the colon and in the blood. We demonstrate Treg activity and show these cells to be activated by microbiota; we identify F. prausnitzii, a core Clostridium strain of the human gut microbiota, as a major inducer of these Treg cells. Interestingly, there are fewer F. prausnitzii in individuals suffering from inflammatory bowel disease (IBD), and accordingly the CD4CD8αα T cells are decreased in the blood and gut of patients with IBD. We argue that CD4CD8αα colonic Treg probably help control or prevent IBD. These data open the road to new diagnostic and therapeutic strategies for the management of IBD and provide new tools to address the impact of the intestinal microbiota on the human immune system