622 research outputs found

    Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types.

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    Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified

    Rorc restrains the potency of ST2+ regulatory T cells in ameliorating intestinal graft-versus-host disease

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    Soluble stimulation-2 (ST2) is increased during graft-versus-host disease (GVHD), while Tregs that express ST2 prevent GVHD through unknown mechanisms. Transplantation of Foxp3- T cells and Tregs that were collected and sorted from different Foxp3 reporter mice indicated that in mice that developed GVHD, ST2+ Tregs were thymus derived and predominantly localized to the intestine. ST2-/- Treg transplantation was associated with reduced total intestinal Treg frequency and activation. ST2-/- versus WT intestinal Treg transcriptomes showed decreased Treg functional markers and, reciprocally, increased Rorc expression. Rorc-/- T cells transplantation enhanced the frequency and function of intestinal ST2+ Tregs and reduced GVHD through decreased gut-infiltrating soluble ST2-producing type 1 and increased IL-4/IL-10-producing type 2 T cells. Cotransfer of ST2+ Tregs sorted from Rorc-/- mice with WT CD25-depleted T cells decreased GVHD severity and mortality, increased intestinal ST2+KLRG1+ Tregs, and decreased type 1 T cells after transplantation, indicating an intrinsic mechanism. Ex vivo IL-33-stimulated Tregs (TregIL-33) expressed higher amphiregulin and displayed better immunosuppression, and adoptive transfer prevented GVHD better than control Tregs or TregIL-33 cultured with IL-23/IL-17. Amphiregulin blockade by neutralizing antibody in vivo abolished the protective effect of TregIL-33. Our data show that inverse expression of ST2 and RORÎłt in intestinal Tregs determines GVHD and that TregIL-33 has potential as a cellular therapy avenue for preventing GVHD

    Everolimus-eluting stents or bypass surgery for multivessel coronary disease

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    Copyright © 2015 Massachusetts Medical Society. BACKGROUND: Results of trials and registry studies have shown lower long-term mortality after coronary-artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI) among patients with multivessel disease. These previous analyses did not evaluate PCI with second-generation drug-eluting stents. METHODS: In an observational registry study, we compared the outcomes in patients with multivessel disease who underwent CABG with the outcomes in those who underwent PCI with the use of everolimus-eluting stents. The primary outcome was all-cause mortality. Secondary outcomes were the rates of myocardial infarction, stroke, and repeat revascularization. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. RESULTS: Among 34,819 eligible patients, 9223 patients who underwent PCI with everolimus-eluting stents and 9223 who underwent CABG had similar propensity scores and were included in the analyses. At a mean follow-up of 2.9 years, PCI with everolimus-eluting stents, as compared with CABG, was associated with a similar risk of death (3.1% per year and 2.9% per year, respectively; hazard ratio, 1.04; 95% confidence interval [CI], 0.93 to 1.17; P = 0.50), higher risks of myocardial infarction (1.9% per year vs. 1.1% per year; hazard ratio, 1.51; 95% CI, 1.29 to 1.77; P<0.001) and repeat revascularization (7.2% per year vs. 3.1% per year; hazard ratio, 2.35; 95% CI, 2.14 to 2.58; P<0.001), and a lower risk of stroke (0.7% per year vs. 1.0% per year; hazard ratio, 0.62; 95% CI, 0.50 to 0.76; P<0.001). The higher risk of myocardial infarction with PCI than with CABG was not significant among patients with complete revascularization but was significant among those with incomplete revascularization (P = 0.02 for interaction). CONCLUSIONS: In a contemporary clinical-practice registry study, the risk of death associated with PCI with everolimus-eluting stents was similar to that associated with CABG. PCI was associated with a higher risk of myocardial infarction (among patients with incomplete revascularization) and repeat revascularization but a lower risk of stroke. (Funded by Abbott Vascular.)published_or_final_versio

    DPS1 regulates cuticle development and leaf senescence in rice

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    AbstractLeaves are the primary food‐producing organs for a plant that carry out photosynthesis and contribute to biomass and grain yield. Leaf senescence is a developmentally regulated physiological process but early leaf senescence is known to negatively affect plant yield. The cuticle is an outer waxy protective layer on the leaf surface which protects plants from pathogens attack as well as dehydration. Our understanding of the molecular mechanisms underlying cuticle development and leaf senescence is still immature. The present study reports the role of the DEGENERATED PANICLE AND PARTIAL STERILITY 1 (DPS1) gene encoding a cystathionine ÎČ‐synthase (CBS) domain‐containing protein in cuticle development and leaf senescence in rice. The dps1 loss‐of‐function mutant showed leaf senescence phenotype with twisted leaves, significantly reduced chlorophyll content and degenerated chloroplasts characterized by a reduced number of starch granules and an abundance of osmiophilic bodies. Furthermore, dps1 leaves displayed defective cuticle development, reduced wax and cutin compounds, and lower relative water content as compared with wild type. Physiological assays showed significantly higher accumulation of reactive oxygen species (ROS) accompanied by enhanced DNA fragmentation in dps1 leaves, which could be associated with chloroplast degeneration and defective cuticle development. Transcriptome analysis revealed altered expression of several critical genes related to photosynthesis and wax/cutin pathway. This study revealed a crucial role of DPS1 in regulating leaf cuticle development and senescence by affecting the expression of several genes. Thus, a moderate expression of DPS1 is necessary for better plant growth and productivity

    Topological edge and corner states in Bi fractals on InSb

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    Topological materials hosting metallic edges characterized by integer quantized conductivity in an insulating bulk have revolutionized our understanding of transport in matter. The topological protection of these edge states is based on symmetries and dimensionality. However, only integer-dimensional models have been classified, and the interplay of topology and fractals, which may have a non-integer dimension, remained largely unexplored. Quantum fractals have recently been engineered in metamaterials, but up to present no topological states were unveiled in fractals realized in real materials. Here, we show theoretically and experimentally that topological edge and corner modes arise in fractals formed upon depositing thin layers of bismuth on an indium antimonide substrate. Scanning tunneling microscopy reveals the appearance of (nearly) zero-energy modes at the corners of Sierpi\'nski triangles, as well as the formation of outer and inner edge modes at higher energies. Unexpectedly, a robust and sharp depleted mode appears at the outer and inner edges of the samples at negative bias voltages. The experimental findings are corroborated by theoretical calculations in the framework of a continuum muffin-tin and a lattice tight-binding model. The stability of the topological features to the introduction of a Rashba spin-orbit coupling and disorder is discussed. This work opens the perspective to novel electronics in real materials at non-integer dimensions with robust and protected topological states.Comment: Main manuscript 14 pages, supplementary material 34 page

    Three Gorges Dam: Friend or Foe of Riverine Greenhouse Gases?

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    International audienceDams are often regarded as greenhouse gas (GHG) emitters. However, our study indicated that the world's largest dam, the Three Gorges Dam (TGD), has caused significant drops in annual average emissions of CO2_2, CH4_4 and N2_2O over 4300 km along the Yangtze River, accompanied by remarkable reductions in the annual export of CO2_2 (79%), CH4_4 (50%) and N2_2O (9%) to the sea. Since the commencement of its operation in 2003, the TGD has altered the carbonate equilibrium in the reservoir area, enhanced methanogenesis in the upstream, and restrained methanogenesis and denitrification via modifying anoxic habitats through long-distance scouring in the downstream. These findings suggest that 'large-dam effects' are far beyond our previous understanding spatiotemporally, which highlights the fundamental importance of whole-system budgeting of GHGs under the profound impacts of huge dams

    Exploratory spatial data analysis for the identification of risk factors to birth defects

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    BACKGROUND: Birth defects, which are the major cause of infant mortality and a leading cause of disability, refer to "Any anomaly, functional or structural, that presents in infancy or later in life and is caused by events preceding birth, whether inherited, or acquired (ICBDMS)". However, the risk factors associated with heredity and/or environment are very difficult to filter out accurately. This study selected an area with the highest ratio of neural-tube birth defect (NTBD) occurrences worldwide to identify the scale of environmental risk factors for birth defects using exploratory spatial data analysis methods. METHODS: By birth defect registers based on hospital records and investigation in villages, the number of birth defects cases within a four-year period was acquired and classified by organ system. The neural-tube birth defect ratio was calculated according to the number of births planned for each village in the study area, as the family planning policy is strictly adhered to in China. The Bayesian modeling method was used to estimate the ratio in order to remove the dependence of variance caused by different populations in each village. A recently developed statistical spatial method for detecting hotspots, Getis's [Image: see text] [7], was used to detect the high-risk regions for neural-tube birth defects in the study area. RESULTS: After the Bayesian modeling method was used to calculate the ratio of neural-tube birth defects occurrences, Getis's [Image: see text] statistics method was used in different distance scales. Two typical clustering phenomena were present in the study area. One was related to socioeconomic activities, and the other was related to soil type distributions. CONCLUSION: The fact that there were two typical hotspot clustering phenomena provides evidence that the risk for neural-tube birth defect exists on two different scales (a socioeconomic scale at 6.84 km and a soil type scale at 22.8 km) for the area studied. Although our study has limited spatial exploratory data for the analysis of the neural-tube birth defect occurrence ratio and for finding clues to risk factors, this result provides effective clues for further physical, chemical and even more molecular laboratory testing according to these two spatial scales

    Analysis of the geographic distribution of HFRS in Liaoning Province between 2000 and 2005

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    <p>Abstract</p> <p>Background</p> <p>Hemorrhagic fever with renal syndrome (HFRS) is endemic in Liaoning Province, China, and this province was the most serious area affected by HFRS during 2004 to 2005. In this study, we conducted a spatial analysis of HFRS cases with the objective to determine the distribution of HFRS cases and to identify key areas for future public health planning and resource allocation in Liaoning Province.</p> <p>Methods</p> <p>The annual average incidence at the county level was calculated using HFRS cases reported between 2000 and 2005 in Liaoning Province. GIS-based spatial analyses were conducted to detect spatial distribution and clustering of HFRS incidence at the county level, and the difference of relative humidity and forestation between the cluster areas and non-cluster areas was analyzed.</p> <p>Results</p> <p>Spatial distribution of HFRS cases in Liaoning Province from 2000 to 2005 was mapped at the county level to show crude incidence, excess hazard, and spatial smoothed incidence. Spatial cluster analysis suggested 16 and 41 counties were at increased risk for HFRS (p < 0.01) with the maximum spatial cluster sizes at ≀ 50% and ≀ 30% of the total population, respectively, and the analysis showed relative humidity and forestation in the cluster areas were significantly higher than in other areas.</p> <p>Conclusion</p> <p>Some clustering of HFRS cases in Liaoning Province may be etiologically linked. There was strong evidence some HFRS cases in Liaoning Province formed clusters, but the mechanism underlying it remains unknown. In this study we found the clustering was consistent with the relative humidity and amount of forestation, and showed data indicating there may be some significant relationships.</p

    Plasmonic organic solar cell and its absorption enhancement analysis using cylindrical Ag nano-particle model based on finite difference time domain (FDTD)

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    We report the plasmon-assisted photocurrent enhancement in Ag nanoparticles (NPs)-embedded PEDOT:PSS/P3HT:PCBM organic solar cells, and theoretically investigate the causes of the improved optical absorption based on a cylindrical Ag-NPs model which is simulated with a finite difference time domain (FDTD) method. The proposed cylindrical Ag-NPs model is able to explain the optical absorption enhancement by the localized surface plasmon resonance (LSPR) modes, and to provide a further understanding of Ag-NPs shape parameters which play an important role to determine the broadband absorption phenomena in plasmonic organic solar cells

    Temporal and spatial analysis of Neural tube defects and detection of geographical factors in Shanxi Province, China

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    Background: Neural tube defects (NTDs) are congenital birth defects that occur in the central nervous system, and they have the highest incidence among all birth defects. Shanxi Province in China has the world's highest rate of NTDs. Since the 1990s, China's government has worked on many birth defect prevention programs to reduce the occurrence of NTDs, such as pregnancy planning, health education, genetic counseling, antenatal ultrasonography and serological screening. However, the rate of NTDs in Shanxi Province is still higher than the world's average morbidity rate after intervention. In addition, Shanxi Province has abundant coal reserves, and is the largest coal production province in China. The objectives of this study are to determine the temporal and spatial variation of the NTD rate in rural areas of Shanxi Province, China, and identify geographical environmental factors that were associated with NTDs in the risk area. Methods: In this study, Heshun County and Yuanping County in Shanxi Province, which have high incidence of NTDs, were selected as the study areas. Two paired sample T test was used to analyze the changes in the risk of NTDs from the time dimension. Ripley's k function and spatial filtering were combined with geographic information system (GIS) software to study the changes in the risk of NTDs from the spatial dimension. In addition, geographical detectors were used to identify the risk geographical environmental factors of NTDs in the study areas, especially the areas close to the coal sites and main roads. Results: In both Heshun County and Yuanping County, the incidence of NTDs was significantly (P&lt;0.05) reduced after intervention. The results from spatial analysis showed that significant spatial heterogeneity existed in both counties. NTD clusters were still identified in areas close to coal sites and main roads after interventions. This study also revealed that the elevation, fault and soil types always had a larger influence on the incidence of NTDs in our study areas. In addition, distance to the river was a risk factor of NTDs in areas close to the coal sites and main roads. Conclusion: The existing interventions may have played an important role to reduce the incidence of NTDs. However, there is still spatial heterogeneity in both counties after using the traditional intervention methods. The government needs to take more measures to strengthen the environmental restoration to prevent the occurrence of NTDs, especially those areas close to coal sites and main roads. The outcome of this research provides an important theoretical basis and technical support for the government to prevent the occurrence of NTDs
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