Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2(+)TMPRSS2(+) cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

A 'Road Map' for the Development of an Interdisiplinary GIScience Program at Highed Education Institutions

Higher education has been charged with the development of professionals to serve the rapidly developing spatial technology industry, but is just beginning to arrive at a consensus concerning the types of courses, sequence of courses and specialty areas. Geographic Information Science and Technology Body of Knowledge (DiBiase et al., 2006) developed under the auspices of the University Consortium for Geographic Information Science (UCGIS) represents a major step in Geographic Information Science (GIScience) education which may lead to more consistency among programs in Geographic Information Science (GIScience.) Concurrently, there are movements for the accreditation of GIScience programs and formal GIS certificates. However, there is a significant gap from these promising but incipient efforts to the coherent development of GIScience programs at the university, college or technical school level. What should be the direction for those who are developing GIScience programs in institutions of higher education in the absence of more definitive direction? In this confusing transitory environment, the authors in this paper propose an outline or “road map” for the development of an interdisciplinary GIScience program

Anemia and the onset of gout in a population-based cohort of adults: Atherosclerosis Risk in Communities study

10.1186/ar4026Arthritis Research and Therapy144R19

Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review

Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research

The dominance of haptics over audition in controlling wrist velocity during striking movements

Skilled interactions with sounding objects, such as drumming, rely on resolving the uncertainty in the acoustical and tactual feedback signals generated by vibrating objects. Uncertainty may arise from mis-estimation of the objects' geometry-independent mechanical properties, such as surface stiffness. How multisensory information feeds back into the fine-tuning of sound-generating actions remains unexplored. Participants (percussionists, non-percussion musicians, or non-musicians) held a stylus and learned to control their wrist velocity while repeatedly striking a virtual sounding object whose surface stiffness was under computer control. Sensory feedback was manipulated by perturbing the surface stiffness specified by audition and haptics in a congruent or incongruent manner. The compensatory changes in striking velocity were measured as the motor effects of the sensory perturbations, and sensory dominance was quantified by the asymmetry of congruency effects across audition and haptics. A pronounced dominance of haptics over audition suggested a superior utility of somatosensation developed through long-term experience with object exploration. Large interindividual differences in the motor effects of haptic perturbation potentially arose from a differential reliance on the type of tactual prediction error for which participants tend to compensate: vibrotactile force vs. object deformation. Musical experience did not have much of an effect beyond a slightly greater reliance on object deformation in mallet percussionists. The bias towards haptics in the presence of crossmodal perturbations was greater when participants appeared to rely on object-deformation feedback, suggesting a weaker association between haptically sensed object deformation and the acoustical structure of concomitant sound during everyday experience of actions upon objects

Risk factors for incident hyperuricemia during mid-adulthood in African American and White men and women enrolled in the ARIC cohort study

10.1186/1471-2474-14-347BMC Musculoskeletal Disorders1434

Frailty and falls among adult patients undergoing chronic hemodialysis: A prospective cohort study

10.1186/1471-2369-14-224BMC Nephrology14122

Perceptions about hemodialysis and transplantation among African American adults with end-stage renal disease: Inferences from focus groups Epidemiology and Health Outcomes

10.1186/s12882-015-0045-1BMC Nephrology1614