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integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs.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

Momentum scale calibration of the LHCb spectrometer

For accurate determination of particle masses accurate knowledge of the momentum scale of the detectors is crucial. The procedure used to calibrate the momentum scale of the LHCb spectrometer is described and illustrated using the performance obtained with an integrated luminosity of 1.6 fb-1 collected during 2016 in pp running. The procedure uses large samples of J/ψ → μ + μ - and B+ → J/ψ K + decays and leads to a relative accuracy of 3 × 10-4 on the momentum scale

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass

Comparative Gas Exchange Performance During The Wet Season Of Three Brazilian Styrax Species Under Habitat Conditions Of Cerrado Vegetation Types Differing In Soil Water Availability And Crown Density

We studied the influence of environmental conditions in different vegetation types of the Brazilian savanna (cerrado s.l.) on CO2 assimilation and water use efficiency of Styrax ferrugineus, S. camporum and S. pohlii, which are morphologically similar but have distinct distribution patterns. We measured leaf gas exchange and water relations in adult and young plants. Adult plants of S. ferrugineus were measured in the cerrado s. str.; plants of S. camporum at the edge of cerradão, a woodland vegetation; and in a riparian forest those of S. pohlii. Eight-month-old young plants were planted in the cerrado s. str., at the edge and in the understory of the cerradão, and in the understory of the riparian forest. For young plants, the high light availability in the cerrado s. str. resulted in a threefold greater CO2 assimilation rate (A) compared to the other sites. A of adult plants under full irradiation (1800μmolphotonsm-2s-1) was significantly lower in S. pohlii compared to S. ferrugineus and S. camporum. Although sufficient soil water was available at every site at the end of the wet season, the extreme high water content in the riparian forest soil led to increased stomatal conductance (gs) and transpiration rate (E) for young plants of S. camporum and S. pohlii, but not of S. ferrugineus. However, the large gs in S. pohlii and S. camporum young plants did not result in higher A rates. The differences may indicate some specialization of S. ferrugineus to best growth in open savanna and of S. pohlii in riparian forest habitats. The high water use efficiency of S. camporum young plants in the understory of cerradão seems not yet sufficient to emphasize that this species benefits from this particular habitat. Because, while water supply during the wet season is quite sufficient, soil water deficits and frequent fires can occur during the dry season and might modify strongly the habitat conditions for the three Styrax species. © 2010 Elsevier GmbH.2064351359Ackerly, D.D., The evolution of plant ecophysiological traits: recent advances and future directions (2000) Bioscience, 50, pp. 979-995Barrs, H.D., Weatherley, P.E., A re-examination of the relative turgidity technique for estimating water deficits in leaves (1962) Aust. J. Biol. Sci., 15, pp. 413-428Bhaskar, R., Ackerly, D.D., Ecological relevance of minimum seasonal water potentials (2006) Physiol. Plant., 127, pp. 353-359Bieras, A.C., Sajo, M.G., Leaf structure of the cerrado (Brazilian savanna) woody plants (2009) Trees, 23, pp. 451-471Chaves, M.M., How plants cope with water stress in the field. Photosynthesis and growth (2002) Ann. Bot., 89, pp. 907-916Christianini, A.V., Oliveira, P.S., The relevance of ants as seed rescuers of a primarily bird-dispersed tree in the Neotropical cerrado savanna (2009) Oecologia, 160, pp. 735-745Crawford, R.M.M., (1989) Studies in Plant Survival, , Blackwell, OxfordEngelbrecht, B.M.J., Kursar, T.A., Tyree, M.T., Drought effects on seedling survival in a tropical moist forest (2005) Trees, 19, pp. 312-321Engelbrecht, B.M.J., Comita, L.S., Condit, R., Kursar, T.A., Tyree, M.T., Turner, B.L., Hubbell, S.P., Drought sensitivity shapes species distribution patterns in tropical forests (2007) Nature, 447, pp. 80-83Ferreira, L.G., Yoshioka, H., Huete, A., Sano, E.E., Seasonal landscape and spectral vegetation index dynamics in the Brazilian cerrado: an analysis within the large-scale biosphere-atmosphere experiment in Amazônia (LBA) (2003) Rem. Sens. 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Single-cell RNA sequencing reveals profibrotic roles of distinct epithelial and mesenchymal lineages in pulmonary fibrosis

Pulmonary fibrosis (PF) is a form of chronic lung disease characterized by pathologic epithelial remodeling and accumulation of extracellular matrix (ECM). To comprehensively define the cell types, mechanisms, and mediators driving fibrotic remodeling in lungs with PF, we performed single-cell RNA sequencing of single-cell suspensions from 10 nonfibrotic control and 20 PF lungs. Analysis of 114,396 cells identified 31 distinct cell subsets/states. We report that a remarkable shift in epithelial cell phenotypes occurs in the peripheral lung in PF and identify several previously unrecognized epithelial cell phenotypes, including a KRT5−/KRT17+ pathologic, ECM-producing epithelial cell population that was highly enriched in PF lungs. Multiple fibroblast subtypes were observed to contribute to ECM expansion in a spatially discrete manner. Together, these data provide high-resolution insights into the complexity and plasticity of the distal lung epithelium in human disease and indicate a diversity of epithelial and mesenchymal cells contribute to pathologic lung fibrosis

Translocação orgânica, produtividade e rendimento de óleo essencial de Mentha piperita L. cultivada em solução nutritiva com variação dos níveis de N, P, K e Mg Organic translocation, productivity and essential oil yield of Mentha piperita L. cultivated in nutrient solution with varying N, P, K and Mg levels

O estudo objetivou avaliar translocação orgânica, índices fisiológicos da análise de crescimento e rendimento do óleo essencial de Mentha piperita L. cultivada em solução nutritiva com variação dos níveis de N, P, K e Mg. Assim, foram avaliados os quatro tratamentos contendo 50% N, P, K, 25% Mg; 50% N, P, K, Mg; 65%N, 50%P, 25%K, 100% Mg e 100% N, P, K, Mg. A translocação orgânica foi avaliada por meio da determinação da razão de massa foliar (RMF) e da distribuição de massa seca para os diferentes órgãos. Os índices fisiológicos razão de área foliar (RAF), área foliar específica (AFE), taxa assimilatória líquida (TAL) e taxa de crescimento relativo (TCR) derivadas que compõem a análise de crescimento foram estimados pelo programa ANACRES, após ajuste exponencial quadrático da área foliar e massa seca de lâminas foliares e total da planta em relação ao tempo. O rendimento do óleo essencial, em porcentagem, foi calculado após extração da parte aérea por hidrodestilação. As plantas submetidas ao tratamento com nível completo de nutrientes (100%N/P/K/Mg) exportaram com menor eficiência o material orgânico a partir da folha e a RMF mostrou queda mais lenta, devido à retenção desse material por mais tempo no local de sua produção. Além disso, não apresentaram melhor produtividade e as curvas da TAL e TCR mostraram quedas mais lentas. As plantas submetidas ao tratamento com 65%N/50%P/25%K/100%Mg revelaram adequada exportação de matéria orgânica da folha para caule e pecíolos, conforme demonstra a RMF e a distribuição de massa seca para esses órgãos. Revelaram ainda a RAF mais elevada no inicio do desenvolvimento e mais baixa aos 94 DAT, indicando sombreamento das folhas como resultado de seu crescimento. A AFE dessas plantas mostrou menor variação durante o ciclo, refletindo espessura mais constante de suas folhas. A TAL e a TCR apresentaram curvas decrescentes, com quedas bem acentuadas em relação às demais plantas. Todos esses índices indicam melhor produtividade das plantas submetidas ao tratamento 65%N/50%P/25%K/100%Mg, que também apresentaram rendimento de óleo essencial, em média, maior durante o ciclo. Conclui-se que a redução de 35% de N, 50% de P, 75% de K (65%N/50%P/25%K/100%Mg) é indicada para o cultivo e extração de óleo essencial de M. piperita.<br>This study aimed to evaluate organic translocation, physiologic indexes of growth analysis and essential oil yield of Mentha piperita L. cultivated in nutrient solution with varying levels of N, P, K and Mg. Thus, four treatments were evaluated: 50% N, P, K, 25% Mg; 50% N, P, K, Mg; 65% N, 50% P, 25% K, 100% Mg; and 100% N, P, K, Mg. Organic translocation was assessed through leaf mass ratio (LMR) and dry matter distribution to the different organs. The physiologic indexes leaf area ratio (LAR), specific leaf area (SLA), net assimilation rate (NAR) and relative growth rate (RGR), derived from growth analysis, were estimated using the software ANACRES, following the quadratic exponential fitting of leaf area and dry mass of leaves and total plant, relative to time. Essential oil yield was calculated as percentage after extraction from shoot using hydrodistillation. Plants subjected to the treatment with complete level of nutrients (100%N/P/K/Mg) less efficiently exported organic material from the leaf and LMR showed slower decrease due to the longer retention of such material in its production site. Besides, those plants did not present higher productivity and NAR and RGR curves showed slower decrease. Plants subjected to the treatment with 65%N/50%P/25%K/100%Mg had adequate organic matter exportation from the leaves to the stem and petioles, as demonstrated by LMR and dry matter distribution to these organs. Also in these plants, LAR was higher at the initial development and lower at 94 DAT, indicating leaf shading as a result of growth, and SLA showed less variation during the cycle, reflecting more homogeneous leaf thickness. NAR and RGR had decreasing curves, with marked falls relative to the remaining plants. All these indexes indicate higher productivity of plants subjected to the treatment with 65%N/50%P/25%K/100%Mg, which also had higher essential oil yield, on average, during the cycle. In conclusion, 35% reduction for N, 50% for P, 75% for K (65%N/50%P/25%K/100%Mg) is recommended for cultivation and essential oil extraction of M. piperita

Efeito da poda do tipo decote no controle da xylella fastidiosa em cultivares de cafeeiro "Decote" type pruning effect upon xylella fastidiosa control in coffee cultivars

A bactéria Xylella fastidiosa causa prejuízos à cafeicultura e o emprego de produtos químicos, até o presente, não tem possibilitado o controle econômico dessa bactéria. O manejo adequado do cafezal, desde o plantio, com o uso de mudas isentas da bactéria e o controle das cigarrinhas vetoras, são medidas que atenuam a incidência da doença. A utilização de podas, que tem sido recomendada como medida de controle em citros e videiras, não tem ainda eficiência comprovada para o cafeeiro. Neste trabalho, objetivou-se estudar a eficácia do emprego da poda do tipo decote em cafeeiros arábica como controle de X. fastidiosa. Para tanto, após o emprego desse tipo de poda em cafeeiros infectados pela bactéria, quantificou-se a proporção de elementos de vaso do xilema obstruídos pela bactéria, e avaliou-se a severidade dos sintomas externos de infecção provocados pela X. fastidiosa. Oito meses após a aplicação da poda, no mês de junho de 2003 (período seco), observou-se que as plantas estavam com 4% dos elementos de vaso do pecíolo, 2% na nervura principal e 1% no caule obstruído pela X. fastidiosa. No período chuvoso, 14 meses após a poda, a proporção de obstrução dos elementos de vaso diminuiu para 2% no pecíolo, 1% no caule e na nervura principal. A prática da poda diminuiu ligeiramente a proporção de elementos de vaso obstruídos pela bactéria apenas no período seco, uma vez que foi observado antes da poda um máximo de 6% de obstrução no pecíolo. Os novos ramos que brotavam no cafeeiro, na estação chuvosa, pareciam compensar a obstrução dos ramos mais velhos, diminuindo a proporção de obstrução dos elementos de vaso na planta. Em 2003, não houve diferenças na severidade do sintoma externo entre os tratamentos nos dois períodos, seca e chuvoso. Entretanto, no período seco de 2004, as cultivares Catuaí Vermelho IAC 81 e Mundo Novo IAC 515-20, enxertadas sobre o porta-enxerto 'Apoatã IAC 2258' de C. canephora, foram os tratamentos com maior severidade e, novamente no período chuvoso, as diferenças não foram observadas. Concluiu-se, portanto, que a prática da poda do tipo decote não resultou nesse experimento em um controle eficiente da X. fastidiosa em cafeeiros de C. arabica de pé-franco ou enxertados e infectados por esta moléstia.<br>Xylella fastidiosa plant colonization causes damages to the coffee production and nowadays there is no available economic chemical control to this bacterium. Adequate cultivation management as the use of bacteria-free scions and control of the insect vector (cicadas), are practices that may attenuate the disease incidence. Pruning, that has been recommended for citrus and vines for disease control, still does not have its efficiency proved for coffee plants. This research work aimed to quantify the proportion of xylem vessel elements obstructed by the bacteria, as well as to evaluate the disease external symptoms severity after the "decote" type pruning. In June 2003 (dry season), eight months after pruning, it was observed that 4% of the petiole vessel elements were obstructed by X. fastidiosa, 2% of the central vein and 1% of the stem. In the rainy season, 14 months after pruning, the obstruction proportion of vessel elements decreased to 2% in the petiole and to 1% in central vein and stem respectively. Therefore, the pruning practice decreased slightly the xylem vessel obstruction caused by the bacteria in the dry period, once prior to pruning a 6% obstruction in the petiole was observed. The new branches sprouted during the rainy season seemed to compensate obstruction in older branches, thus decreasing vase obstruction proportion. In 2003 there were no differences in the disease symptom severity among treatments in the two periods (dry and rainy season), however, in the dry period of 2004, 'Catuaí Vermelho IAC 81' and 'Mundo Novo IAC 515-20' cultivars, grafted on C. canephora 'Apoatã IAC 2258', presented higher severity and, again in the rainy period, differences were not observed. It was concluded that the "decote" type pruning practice did not result in a X. fastidiosa efficient control