Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation.

Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS) 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex II (CII) and I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking RET in pro-inflammatory myeloid cells protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo . Our data show that RET in myeloid cells is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders 3 .

Biofilm assemblage and activity on plastic in urban streams at a continental scale: Site characteristics are more important than substrate type.

The fate of plastics in rivers is a key component of the global plastic cycle. Plastics entering freshwater ecosystems are colonized by microbial biofilms, and microbe-plastic interactions can influence ecosystem processes and plastic fate. While literature examining the role of geographic region on plastic biofilms is quickly expanding, research which covers large (i.e., continental) spatial scales and includes freshwater ecosystems is warranted. In addition, most research focuses on bacterial communities, while biofilm eukaryotes are less commonly studied. We assessed biofilm metabolism and community structure on plastic (foamed polystyrene and polyvinyl chloride; PVC) and natural substrates (unglazed ceramic tile) in urban streams spanning a nested geographic gradient in the continental United States. We measured biofilm biomass, community respiration, and chlorophyll a, in addition to assessing marker gene-based community diversity of bacterial, fungal, and algal assemblages. Results demonstrated some substrate-specific trends in biofilm characteristics, including higher biofilm biomass on polystyrene across sites, and lower diversity of bacterial assemblages on both types of plastic litter versus tile. However, there were no differences among substrates for chlorophyll, respiration, and the abundance and diversity of algal and fungal assemblages. Thus, we concluded that the primary driver of biofilm metabolism and community composition were site characteristics, rather than substrate type. Additional studies are needed to quantify which site-specific characteristics drive biofilm dynamics on plastic litter in streams (e.g., water chemistry, light, seasonality, hydrology). These results add to the growing literature on the biofilm 'plastisphere' in aquatic ecosystems, demonstrating that the factors which control the assembly and activity of biofilm communities on plastic substrates (including bacteria, algal, and fungal assemblages together) in urban streams are similar to those driving biofilm dynamics on natural substrates.

Atherosclerosis in the young: a virulent disease.

To learn more about the prognosis of young patients with atherosclerotic cardiovascular disease we reviewed our experience with patients 40 years of age or younger who required surgical intervention for cardiovascular occlusive disease. We identified 47 patients, 25 of whom required peripheral vascular reconstruction and 22 of whom underwent coronary artery bypass grafting. All but one patient were extremely heavy cigarette smokers. Of the 11 women with peripheral vascular disease, eight required operations for limb salvage and three for renovascular hypertension. Four of the 11 women required a total of 11 subsequent operations because of recurrent or progressive disease. Of the 14 men, 13 required intervention for limb salvage and one for renovascular hypertension. Forty-five additional operations, including 15 amputations, were required in these 14 male patients because of recurrent or progressive disease. Of the 22 patients (21 men and one woman) who underwent coronary artery bypass operations, there was one postoperative death. Five patients (23.8%) required a second bypass operation and one patient (4.8%) required a third procedure bypass because of recurrent symptoms and occluded grafts. One patient has occluded grafts and inoperable disease. Atherosclerotic cardiovascular disease in young patients appears to be a virulent disease process and is associated with a high rate of recurrent or progressive disease. There is a striking association between the premature development of atherosclerotic cardiovascular disease and cigarette smoking.