Mutations in the hypoxia-inducible factor angiogenin (ANG) have been identified in Amyotrophic Lateral Sclerosis (ALS) patients, but the potential role of ANG in ALS pathogenesis was undetermined. Here we show that angiogenin promotes motoneuron survival both in vitro and in vivo. Angiogenin protected cultured motoneurons against excitotoxic injury in a PI-3-kinase/Akt kinase-dependent manner, whereas knock-down of angiogenin potentiated excitotoxic motoneuron death. Expression of wild-type ANG protected against endoplasmic reticulum (ER) stress-induced and trophic-factor-withdrawal-induced cell death in vitro, whereas the ALS-associated ANG mutant K40I exerted no protective activity and failed to activate Akt-1. In SOD1 G93A mice angiogenin delivery increased lifespan and motoneuron survival, restored the disease-associated decrease in Akt-1 survival signaling, and reversed a pathophysiological increase in ICAM-1 expression. Our data demonstrate that angiogenin is a key factor in the control of motoneuron survival.

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Rising prevalence of diabetes worldwide has necessitated the implementation of population-based diabetic retinopathy (DR) screening programs that can perform retinal imaging and interpretation for extremely large patient cohorts in a rapid and sensitive manner while minimizing inappropriate referrals to retina specialists. While most current screening programs employ mydriatic or nonmydriatic color fundus photography and trained image graders to identify referable DR, new imaging modalities offer significant improvements in diagnostic accuracy, throughput, and affordability. Smartphone-based fundus photography, macular optical coherence tomography, ultrawide-field imaging, and artificial intelligence-based image reading address limitations of current approaches and will likely become necessary as DR becomes more prevalent. Here we review current trends in imaging for DR screening and emerging technologies that show potential for improving upon current screening approaches.

Our study identified the imaging parameters that determined the repeatability of quantitative retinal vessel density measurements. These findings have implications in determining if OCT-A images can be used to accurately evaluate serial changes in retinal vessel density.

Volume 80, no. 1, p. [85][86][87][88][89][90][91][92][93][94] 2006. Page 86: We have recently realized that a protein sequence alignment comparing the B2 proteins of greasy grouper nervous necrosis virus (GGNNV) and flock house virus (FHV) is erroneous. The FHV sequence used in the article was not that of B2 but rather the frameshifted B1 protein. We have corrected the alignment using the FHV B2 sequence. Our conclusions regarding the low level of sequence similarity between the two proteins remain unchanged. The updated Fig. 1 and legend are shown below.FIG. 1. Amino acid sequences derived from previously published sequences (9, 16, 28) were aligned by using ClustalW, yielding sequence identities of 10.2 and 6.6% and similarities of 13.9 and 16.0% to NoV and FHV, respectively. 4909on May 9, 2018 by guest