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Luengo et al. (2020) demonstrate that pyruvate dehydrogenase (PDH) overactivation blunts NAD+ regeneration by overcharging the mitochondrial membrane potential and driving ATP synthesis beyond demand. Under these conditions, some cells prioritize aerobic glycolysis to meet the need for oxidized cofactors in biosynthetic metabolism.As part of our commitment to amplifying the voices of underrepresented scientists, we are publishing the insights and experiences of a panel of underrepresented scientists. Here, they discuss the impact of racial bias and share strategies for addressing it. These are the personal opinions of the authors and may not reflect the views of their institutions.Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.Firefighting is associated with an increased risk for a cardiovascular (CV) event, likely due to increased CV strain. The increase in CV strain during firefighting can be attributed to the interaction of several factors such as the strenuous physical demand, sympathetic nervous system activation, increased thermal burden, and the environmental exposure to smoke pollutants. Characterizing the impact of varying thermal burden and pollutant exposure on hemodynamics may help understand the CV burden experienced during firefighting. The purpose of this study was to examine the hemodynamic response of firefighters to training environments created by pallets and straw; oriented strand board (OSB); or simulated fire/smoke (fog). Twenty-three firefighters had brachial blood pressure measured and central blood pressure and hemodynamics estimated from the pressure waveform at baseline, and immediately and 30 minutes after each scenario. The training environment did not influence the hemodynamic response over time (interaction, p > 0.05); however, OSB scenarios resulted in higher pulse wave velocity and blood pressure (environment, p less then 0.05). In conclusion, conducting OSB training scenarios appears to create the largest arterial burden in firefighters compared to other scenarios in this study. Environmental thermal burden in combination with the strenuous exercise, and psychological and environmental stress placed on firefighters should be considered when designing fire training scenarios and evaluating CV risk.Patients with chronic limb-threatening ischemia (CLTI) face numerous barriers to caring for lower extremity wounds. We explored the perceptions of CLTI patients to their wound/management and sought to determine attitudes towards their vascular provider as well as willingness for management through telemedicine. Patients admitted to hospital for treatment of Rutherford Grade 5 and 6 CLTI were asked complete a wound evaluation survey and took part in a semi-structured interview. Semi-structured interviews were recorded, transcribed, and analyzed using an inductive coding strategy. Codes were grouped for thematic analysis and aggregated into assertions. Eleven patients with a mean age of 60 years (35-79 years) were interviewed. All patients had peripheral artery disease (PAD) and eight patients had diabetes as well. Three overarching themes were identified. First, patients appear to have limited coping mechanisms and are overwhelmed by the care of their wounds. Second, in this cohort of patients, many had become passive observers of their care as demonstrated by a limited understanding of their disease processes and detachment from wound management. The third theme was how strong the desire to do everything to prevent limb loss was, but patients acknowledged this is hard to translate into real life with limited resources. Patients with CLTI have concerns that vascular providers must recognize and address to build strong patient-provider relationships and increase activation for management of their wounds and other medical conditions. Patients who have access to technology and with guidance may be able to understand getting care through remote medicine.Exposure to prolonged sitting increases blood pooling and the risk of lower-extremity vascular arterial and venous complications, including deep vein thrombosis. Compression garment stockings (CGS) may prevent pooling, thereby mitigating the associated vascular complications. Three aims were addressed (i) does use of CGS help to prevent blood pooling; (ii) does blood pooling correlate with decreased stroke volume; and (iii) does use of CGS preserve leg arterial flow-mediated dilation and reactive hyperemia response. Twenty inactive participants (22 ± 4 years, 30% female, 22.1 ± 2.0 kg/m2) were randomized to sit for 3 hours with (CGS) and without use of CGS. Blood pooling was determined using medial gastrocnemius total hemoglobin. Stroke volume was estimated using finger photoplethysmography, respectively. Macrovascular and microvascular function were measured using popliteal artery flow-mediated dilation and reactive hyperemia, respectively. In response to 3 hours of sitting (i) there was an interaction effect for total hemoglobin (p less then 0.001); the condition without use of CGS increased 10.5% (95% CI 6.7 to 14.3) and CGS increased 4.3% (95% CI 0.1 to 7.7); (ii) blood pooling was negatively associated with stroke volume (r = -0.58, 95% CI -0.68 to -0.45); (iii) reactive hyperemia and flow-mediated arterial dilation was impaired after prolonged sitting, and use of CGS was not associated with attenuation of this impairment. Use of CGS decreases blood pooling but does not preserve arterial macrovascular and microvascular responses to prolonged sitting. Further study is warranted to determine whether CGS has additive benefits when combined with sitting interruption strategies.In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit theburden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity.Purpose The extant literature suggests that individual differences in speech perception can be linked to broad receptive language phenotype. For example, a recent study found that individuals with a smaller receptive vocabulary showed diminished lexically guided perceptual learning compared to individuals with a larger receptive vocabulary. Here, we examined (a) whether such individual differences stem from variation in reliance on lexical information or variation in perceptual learning itself and (b) whether a relationship exists between lexical recruitment and lexically guided perceptual learning more broadly, as predicted by current models of lexically guided perceptual learning. Method In Experiment 1, adult participants (n = 70) completed measures of receptive and expressive language ability, lexical recruitment, and lexically guided perceptual learning. In Experiment 2, adult participants (n = 120) completed the same lexical recruitment and lexically guided perceptual learning tasks to provide a high-pobetween these two constructs.Rationale Randomized controlled trials do not support a role for continuous positive airway pressure (CPAP) in preventing major cardiovascular events or mortality in patients with obstructive sleep apnea (OSA). However, these trials' setting does not apply to most CPAP-treated patients. Objectives We aimed to assess the effect of CPAP on mortality in real-world patients. see more Methods We performed a population-based longitudinal observational study including all patients with OSA prescribed CPAP during 2011 in Catalonia, Spain, and non-OSA control subjects matched (12) by sex, 5-year age group, and region who were followed from 2011 to 2016. Results A total of 9,317 CPAP-treated patients with OSA and 18,370 control subjects without OSA were included (median age, 67 [57-72] years; 74% male). During a median follow-up of 5.5 years, 2,301 deaths were recorded. After adjustment by a composite of diagnosed comorbidities and previous use of healthcare resources, CPAP-treated patients showed a lower risk of death than control subjects (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.61-0.74), with the association not being statistically significant in women. Cancer-related deaths were the main drivers of this association (men HR, 0.44; 95% CI, 0.36-0.54; women HR, 0.44; 95% CI, 0.28-0.68). No significant associations were found for cardiovascular-related deaths. CPAP-treated women had an increased risk of respiratory-related death (HR, 2.41; 95% CI, 1.37-4.23). Conclusions CPAP-treated patients had a lower mortality rate than control subjects. This relationship was driven by cancer-related, but not cardiovascular-related, deaths. Results suggest a role for sex when prescribing CPAP, especially considering respiratory-related deaths, and foster a debate on the relationship between OSA and cardiovascular outcomes.Intricate relationships between endocytosis and cellular signaling, first recognized nearly 40 years ago through the study of tyrosine kinase growth factor receptors, are now known to exist for multiple receptor classes and to affect myriad physiological and developmental processes. This review summarizes our present understanding of how endocytosis orchestrates cellular signaling networks, with an emphasis on mechanistic underpinnings and focusing on two receptor classes-tyrosine kinase and G protein-coupled receptors-that have been investigated in particular detail. Together, these examples provide a useful survey of the current consensus, uncertainties, and controversies in this rapidly advancing area of cell biology.