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We recommend upgrading to the latest version of Internet Explorer , Google Chrome , or Firefox × Latest issue: January 30, 2020 Exenatide induces frataxin expression and improves mitochondrial function in Friedreich ataxia In the issue Local photoreceptor degeneration causes local pathophysiological remodeling of retinal neurons Bristol Denlinger, … , Daniel Palanker, Richard H. Kramer Bristol Denlinger, … , Daniel Palanker, Richard H. Kramer Focal photoreceptor disruption in a rat model of AMD causes local retinoic acid receptor (RAR)-induced pathophysiology, implicating RAR as a therapeutic target for improving vision. Local photoreceptor degeneration causes local pathophysiological remodeling of retinal neurons Text PDF Abstract Vision loss in age-related macular degeneration (AMD) stems from disruption of photoreceptor cells in the macula, the central retinal area required for high-acuity vision. Mice and rats have no macula, but surgical insertion of a subretinal implant can induce localized photoreceptor degeneration due to chronic separation from retinal pigment epithelium, simulating a key aspect of AMD. We find that the implant-induced loss of photoreceptors in rat retina leads to local changes in the physiology of downstream retinal ganglion cells (RGCs), similar to changes in RGCs of rodent models of retinitis pigmentosa (RP), an inherited disease causing retina-wide photoreceptor degeneration. The local implant-induced changes in RGCs include enhanced intrinsic excitability leading to accelerated spontaneous firing, increased membrane permeability to fluorescent dyes, and enhanced photosensitization by azobenzene photoswitches. The local physiological changes are correlated with an increase in retinoic acid receptor–induced (RAR-induced) gene transcription, the key process underlying retinal remodeling in mouse models of RP. Hence the loss of photoreceptors, whether by local physical perturbation or by inherited mutation, leads to a stereotypical set of pathophysiological consequences in RGCs. These findings implicate RAR as a possible common therapeutic target for reversing the signal-corrupting effects of retinal remodeling in both RP and AMD. Authors Bristol Denlinger, Zachary Helft, Michael Telias, Henri Lorach, Daniel Palanker, Richard H. Kramer × Genetic and pathogenic diversity of severe fever with thrombocytopenia syndrome virus (SFTSV) in South Korea Seok-Min Yun, … , Joo-Yeon Lee, Young Ki Choi Seok-Min Yun, … , Joo-Yeon Lee, Young Ki Choi Diverse genotypes of SFTSV were found co-circulating in South Korea, and virus genotype and patient age were found to associate with the case fatality rate. Genetic and pathogenic diversity of severe fever with thrombocytopenia syndrome virus (SFTSV) in South Korea Text PDF Abstract To investigate nationwide severe fever with thrombocytopenia syndrome virus (SFTSV) infection status, we isolated SFTSVs from patients with suspected severe fever with thrombocytopenia syndrome (SFTS) in 207 hospitals throughout South Korea between 2013 and April 2017. A total of 116 SFTSVs were isolated from 3137 SFTS-suspected patients, with an overall 21.6% case fatality rate. Genetic characterization revealed that at least 6 genotypes of SFTSVs were co-circulating in South Korea, with multiple reassortments among them. Of these, the genotype B-2 strains were the most prevalent, followed by the A and F genotypes. Clinical and epidemiologic investigations revealed that genotype B strains were associated with the highest case fatality rate, while genotype A caused only one fatality among 10 patients. Further, ferret infection studies demonstrated varying clinical manifestations and case mortality rates with different strains of SFTSV, which suggests this virus could exhibit genotype-dependent pathogenicity. Authors Seok-Min Yun, Su-Jin Park, Young-Il Kim, Sun-Whan Park, Min-Ah Yu, Hyeok-Il Kwon, Eun-Ha Kim, Kwang-Min Yu, Hye Won Jeong, Jungsang Ryou, Won-Ja Lee, Youngmee Jee, Joo-Yeon Lee, Young Ki Choi × β 1 Integrin regulates adult lung alveolar epithelial cell inflammation Erin J. Plosa, … , Timothy S. Blackwell, Roy Zent Erin J. Plosa, … , Timothy S. Blackwell, Roy Zent Epithelial β1 Integrins play a role in alveolar homeostasis through the regulation of alveolar epithelial cell inflammation. β 1 Integrin regulates adult lung alveolar epithelial cell inflammation Text PDF Abstract Integrins, the extracellular matrix receptors that facilitate cell adhesion and migration, are necessary for organ morphogenesis; however, their role in maintaining adult tissue homeostasis is poorly understood. To define the functional importance of β1 integrin in adult mouse lung, we deleted it after completion of development in type 2 alveolar epithelial cells (AECs). Aged β1 integrin–deficient mice exhibited chronic obstructive pulmonary disease–like (COPD-like) pathology characterized by emphysema, lymphoid aggregates, and increased macrophage infiltration. These histopathological abnormalities were preceded by β1 integrin–deficient AEC dysfunction such as excessive ROS production and upregulation of NF-κB–dependent chemokines, including CCL2. Genetic deletion of the CCL2 receptor, Ccr2, in mice with β1 integrin–deficient type 2 AECs impaired recruitment of monocyte-derived macrophages and resulted in accelerated inflammation and severe premature emphysematous destruction. The lungs exhibited reduced AEC efferocytosis and excessive numbers of inflamed type 2 AECs, demonstrating the requirement for recruited monocytes/macrophages in limiting lung injury and remodeling in the setting of a chronically inflamed epithelium. These studies support a critical role for β1 integrin in alveolar homeostasis in the adult lung. Authors Erin J. Plosa, John T. Benjamin, Jennifer M. Sucre, Peter M. Gulleman, Linda A. Gleaves, Wei Han, Seunghyi Kook, Vasiliy V. Polosukhin, Scott M. Haake, Susan H. Guttentag, Lisa R. Young, Ambra Pozzi, Timothy S. Blackwell, Roy Zent × MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity Tana S. Pottorf, … , James E. Vath, Pamela V. Tran Tana S. Pottorf, … , James E. Vath, Pamela V. Tran Inhibition of methionine aminopeptidase 2 in a ciliopathy mouse model of obesity reduces food intake, body weight, and adiposity and substantially improves metabolic indices. MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity Text PDF Abstract iliopathies Bardet-Biedl syndrome and Alström syndrome are genetically inherited pleiotropic disorders with hyperphagia and obesity as primary clinical features. Methionine aminopeptidase 2 inhibitors (MetAP2i) have been shown in preclinical and clinical studies to reduce food intake, body weight, and adiposity. Here, we investigated the effects of MetAP2i administration in a mouse model of ciliopathy produced by conditional deletion of the Thm1 gene in adulthood. Thm1 conditional knockout (cko) mice showed decreased hypothalamic proopiomelanocortin expression as well as hyperphagia, obesity, metabolic disease, and hepatic steatosis. In obese Thm1-cko mice, 2-week administration of MetAP2i reduced daily food intake and reduced body weight 17.1% from baseline (vs. 5% reduction for vehicle). Th...