Age-related macular degeneration (AMD) is the leading cause of blindness among the elderly. Dry AMD has unclear etiology and no treatment. Lipid-rich drusen are the hallmark of dry AMD. An AMD mouse model and insights into drusenogenesis are keys to better understanding of this disease. Chloride intracellular channel 4 (CLIC4) is a pleomorphic protein regulating diverse biological functions. Here we show that retinal pigment epithelium (RPE)-specific Clic4 knockout mice exhibit a full spectrum of functional and pathological hallmarks of dry AMD. Multidisciplinary longitudinal studies of disease progression in these mice support a mechanistic model that links RPE cell-autonomous aberrant lipid metabolism and transport to drusen formation.

Background: The 2018 United-Network-for-Organ-Sharing (UNOS) allocation-system changes resulted in greater recognition of mechanical circulatory support (MCS), leading to more heart transplantations (HTx) in patients with MCS. We aimed to investigate the effect of the new UNOS allocation system on the need for a permanent pacemaker and associated complications following HTx. Methods: The UNOS Registry was questioned, to identify patients that received HTx in the US between 2000 and 2021. The primary objectives were to identify risk factors for the need for a pacemaker implantation following HTx. Results: 49,529 HTx patients were identified, 1421 (2.9%) requiring a pacemaker post-HTx. Patients who required a pacemaker were older (53.9 ± 11.5 vs. 52.6 ± 12.8 years, p < 0.001), more frequently white (73% vs. 67%; p < 0.001) and less frequently black (18% vs. 20%; p < 0.001). In the pacemaker group, UNOS status 1A (46% vs. 41%; p < 0.001) and 1B (31% vs. 27%; p < 0.001) were more prevalent, and donor age was higher (34.4 ± 12.4 vs. 31.8 ± 11.5 years; p < 0.001). One-year survival was no different between the groups (HR: 1.08; 95% CI: 0.85, 1.37; p = 0.515). An era effect was observed (per year: OR: 0.97; 95% CI: 0.96, 0.98; p = 0.003), while ECMO pre-transplant was associated with lower risk of a pacemaker (OR: 0.41; 95% CI: 0.19, 0.86; p < 0.001). Conclusions: While associated with various patient and transplant characteristics, pacemaker implantation does not seem to impact one-year survival after HTx. The need for pacemaker implantation was lower in the more recent era and in patients who required ECMO pre-transplant, a finding explained by recent advances in perioperative care.

We describe three newly isolated phages—Obliviate, UmaThurman, and Guacamole—that infect Gordonia terrae 3612. The three genomes are related to one another but are not closely related to other previously sequenced phages or prophages. The three phages are predicted to use integration-dependent immunity systems as described in several mycobacteriophages.

A variety of visual cues can trigger defensive reactions in mice (De Franceschi et al. 2016; Evans et al. 2018; Huang et al. 2017; Salay et al. 2018; Shang et al. 2018; Shang et al. 2015; Wei et al. 2015; Yilmaz and Meister 2013; Zhao et al. 2014) and other species (Budnik et al. 2016; Dick et al. 2017; Dunn et al. 2016; Jang et al. 2016; Sen et al. 2017; Shragai et al. 2017; Simmons et al. 2013; Temizer et al. 2015; Wu et al. 2016; Yamawaki 2018; Yin et al. 2018). In mice, looming stimuli that mimic an approaching aerial predator elicit flight or freezing reactions, while sweeping stimuli that mimic an aerial predator flying parallel to the ground typically elicit freezing. The retinal ganglion cell (RGC) types involved in these circuits are largely unknown. We previously discovered that loss of RGC subpopulations in Brn3b knockout mice results in distinct visual response deficits. Here, we report that retinal or global loss of Brn3b selectively ablate the fleeing response to looming stimuli while leaving the freeze response intact. In contrast, freezing responses to sweeping stimuli are significantly affected. Genetic manipulations removing three RGC subpopulations (Brn3a+ betta RGCs, Opn4+Brn3b+ and Brn3c+Brn3b+ RGCs) result in milder phenocopies of Brn3b KO response deficits. These findings show that flight and freezing responses to distinct visual cues are mediated by circuits that can already be separated at the level of the retina, potentially by enlisting dedicated RGC types.