Intact RNA structurome reveals mRNA structure-mediated regulation of miRNA cleavage in vivo

[EN] MicroRNA (miRNA)-mediated cleavage is involved in numerous essential cellular pathways. miRNAs recognize target RNAs via sequence complementarity. In addition to complementarity, in vitro and in silico studies have suggested that RNA structuremay influence the accessibility of mRNAs to miRNA-induced silencing complexes (miRISCs), thereby affecting RNA silencing. However, the regulatory mechanism of mRNA structure in miRNA cleavage remains elusive. We investigated the role of in vivo RNA secondary structure in miRNA cleavage by developing the new CAP-STRUCTURE-seq method to capture the intact mRNA structurome in Arabidopsis thaliana. This approach revealed that miRNA target sites were not structurally accessible for miRISC binding prior to cleavage in vivo. Instead, we found that the unfolding of the target site structure plays a key role in miRISC activity in vivo. We found that the single-strandedness of the two nucleotides immediately downstream of the target site, named Target Adjacent nucleotideMotif, can promotemiRNA cleavage but not miRNA binding, thus decoupling target site binding from cleavage. Our findings demonstrate that mRNA structure in vivo can modulate miRNA cleavage, providing evidence of mRNA structure-dependent regulation of biological processes.Biotechnology and Biological Sciences Research Council [BB/L025000/1]; the NorwichResearch Park Science Links Seed Fund; and European Commission Horizon 2020 European Research Council, Starting Grant [680324]. Funding for open access charge: Biotechnology and Biological Sciences Research Council [BB/L025000/1]; the Norwich Research Park Science Links Seed Fund; and European Commission Horizon 2020 European Research Council, Starting Grant [680324].Yang, M.; Woolfenden, HC.; Zhang, Y.; Fang, X.; Liu, Q.; Vigh, ML.; Cheema, J.... (2020). 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Nanowired human cardiac organoid transplantation enables highly efficient and effective recovery of infarcted hearts

Human cardiac organoids hold remarkable potential for cardiovascular disease modeling and human pluripotent stem cell–derived cardiomyocyte (hPSC-CM) transplantation. Here, we show cardiac organoids engineered with electrically conductive silicon nanowires (e-SiNWs) significantly enhance the therapeutic efficacy of hPSC-CMs to treat infarcted hearts. We first demonstrated the biocompatibility of e-SiNWs and their capacity to improve cardiac microtissue engraftment in healthy rat myocardium. Nanowired human cardiac organoids were then engineered with hPSC-CMs, nonmyocyte supporting cells, and e-SiNWs. Nonmyocyte supporting cells promoted greater ischemia tolerance of cardiac organoids, and e-SiNWs significantly improved electrical pacing capacity. After transplantation into ischemia/reperfusion–injured rat hearts, nanowired cardiac organoids significantly improved contractile development of engrafted hPSC-CMs, induced potent cardiac functional recovery, and reduced maladaptive left ventricular remodeling. Compared to contemporary studies with an identical injury model, greater functional recovery was achieved with a 20-fold lower dose of hPSC-CMs, revealing therapeutic synergy between conductive nanomaterials and human cardiac organoids for efficient heart repair

Variation of size-segregated particle number concentrations in wintertime Beijing

The spatial and temporal variability of the number size distribution of aerosol particles is an indicator of the dynamic behavior of Beijing's atmospheric pollution cocktail. This variation reflects the strength of different primary and secondary sources, such as traffic and new particle formation, as well as the main processes affecting the particle population. In this paper, we report size-segregated particle number concentrations observed at a newly developed Beijing station during the winter of 2018. Our measurements covered particle number size distributions over the diameter range of 1.5 nm-1 mu m (cluster mode, nucleation mode, Aitken mode and accumulation mode), thus being descriptive of a major fraction of the processes taking place in the atmosphere of Beijing. Here we focus on explaining the concentration variations in the observed particle modes, by relating them to the potential aerosol sources and sinks, and on understanding the connections between these modes. We considered haze days and new particle formation event days separately. Our results show that during the new particle formation (NPF) event days increases in cluster mode particle number concentration were observed, whereas during the haze days high concentrations of accumulation mode particles were present. There was a tight connection between the cluster mode and nucleation mode on both NPF event and haze days. In addition, we correlated the particle number concentrations in different modes with concentrations of trace gases and other parameters measured at our station. Our results show that the particle number concentration in all the modes correlated with NOx, which reflects the contribution of traffic to the whole submicron size range. We also estimated the contribution of ion-induced nucleation in Beijing, and we found this contribution to be negligible.Peer reviewe

High-yield single-step catalytic growth of graphene nanostripes by plasma enhanced chemical vapor deposition

We report a single-step growth process of graphene nanostripes (GNSPs) by adding certain substituted aromatics (e.g., 1,2-dichlorobenzene) as precursors during the plasma enhanced chemical vapor deposition (PECVD). Without any active heating and by using low plasma power (≤60 W), we are able to grow GNSPs vertically with high yields up to (13 ± 4) g/m^2 in 20 min. These GNSPs exhibit high aspect ratios (from 10:1 to >∼130:1) and typical widths from tens to hundreds of nanometers on various transition-metal substrates. The morphology, electronic properties and yields of the GNSPs can be controlled by the growth parameters (e.g., the species of seeding molecules, compositions and flow rates of the gases introduced into the plasma, plasma power, and the growth time). Studies of the Raman spectra, scanning electron microscopy images, ultraviolet photoelectron spectroscopy, transmission electron microscopy images, energy-dispersive x-ray spectroscopy and electrical conductivity of these GNSPs as functions of the growth parameters confirm high-quality GNSPs with electrical mobility ∼10^4 cm^2/V-s. These results together with residual gas analyzer spectra and optical emission spectroscopy taken during PECVD growth suggest the important roles of both substituted aromatics and hydrogen plasma in the rapid vertical growth of GNSPs with large aspect ratios

High-yield single-step catalytic growth of graphene nanostripes by plasma enhanced chemical vapor deposition

We report a single-step growth process of graphene nanostripes (GNSPs) by adding certain substituted aromatics (e.g., 1,2-dichlorobenzene) as precursors during the plasma enhanced chemical vapor deposition (PECVD). Without any active heating and by using low plasma power (≤60 W), we are able to grow GNSPs vertically with high yields up to (13 ± 4) g/m^2 in 20 min. These GNSPs exhibit high aspect ratios (from 10:1 to >∼130:1) and typical widths from tens to hundreds of nanometers on various transition-metal substrates. The morphology, electronic properties and yields of the GNSPs can be controlled by the growth parameters (e.g., the species of seeding molecules, compositions and flow rates of the gases introduced into the plasma, plasma power, and the growth time). Studies of the Raman spectra, scanning electron microscopy images, ultraviolet photoelectron spectroscopy, transmission electron microscopy images, energy-dispersive x-ray spectroscopy and electrical conductivity of these GNSPs as functions of the growth parameters confirm high-quality GNSPs with electrical mobility ∼10^4 cm^2/V-s. These results together with residual gas analyzer spectra and optical emission spectroscopy taken during PECVD growth suggest the important roles of both substituted aromatics and hydrogen plasma in the rapid vertical growth of GNSPs with large aspect ratios

Endogenous DOPA inhibits melanoma through suppression of CHRM1 signaling

Melanoma risk is 30 times higher in people with lightly pigmented skin versus darkly pigmented skin. Using primary human melanocytes representing the full human skin pigment continuum and preclinical melanoma models, we show that cell-intrinsic differences between dark and light melanocytes regulate melanocyte proliferative capacity and susceptibility to malignant transformation, independent of melanin and ultraviolet exposure. These differences result from dihydroxyphenylalanine (DOPA), a melanin precursor synthesized at higher levels in melanocytes from darkly pigmented skin. We used both high-throughput pharmacologic and genetic in vivo CRISPR screens to determine that DOPA limits melanocyte and melanoma cell proliferation by inhibiting the muscarinic acetylcholine receptor M1 (CHRM1) signaling. Pharmacologic CHRM1 antagonism in melanoma leads to depletion of c-Myc and FOXM1, both of which are proliferation drivers associated with aggressive melanoma. In preclinical mouse melanoma models, pharmacologic inhibition of CHRM1 or FOXM1 inhibited tumor growth. CHRM1 and FOXM1 may be new therapeutic targets for melanoma

TRABAJOS DE MÉTODO ARQUEOLÓGICO [Material gráfico]

Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte, 201