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List of N-Myc-binding gene promoters at which H3K4me3 was reduced by WDR5 siRNA.

List of N-Myc non-binding gene promoters at which H3K4me3 was reduced by WDR5 siRNA.

List of N-Myc-binding gene promoters at which H3K4me3 was not reduced by WDR5 siRNA.

Supplementary Methods-Figures-Tables

Genes differentially down- or up-regulated by WDR5 siRNAs by more than 1.5 fold, as shown by Affymetrix microarray, in BE(2)-C neuroblastoma cells 40 hours after siRNA transfection.

List of N-Myc non-binding gene promoters at which H3K4me3 was not reduced by WDR5 siRNA.

Robust, generalizable approaches to identify compounds efficiently with undesirable mechanisms of action in complex cellular assays remain elusive. Such a process would be useful for hit triage during high-throughput screening and, ultimately, predictive toxicology during drug development. We generated cell painting and cellular health profiles for 218 prototypical cytotoxic and nuisance compounds in U-2 OS cells in a concentration-response format. A diversity of compounds causing cellular damage produced bioactive cell painting morphologies, including cytoskeletal poisons, genotoxins, nonspecific electrophiles, and redox-active compounds. Further, we show that lower quality lysine acetyltransferase inhibitors and nonspecific electrophiles can be distinguished from more selective counterparts. We propose that the purposeful inclusion of cytotoxic and nuisance reference compounds such as those profiled in this Resource will help with assay optimization and compound prioritization in complex cellular assays like cell painting.

These data are the R scripts, environments, output used for analyzing chemoproteomics data. The volcano plot shown in the manuscript is based on the DEP R package. To validate the enrichment output from DEP, the proteomics data was also processed with the proDA package. Filename (7 files) Description combined_protein_Int.txt Output from database search hdac6_dep_submitted.R script used to process data (from DEP package) hdac6_dep_submitted.R.RData workspace environment from DEP package hdac6probecontrol_dep.csv exported list of p-value and fold-change from DEP hdac6probecontrol_proda.csv exported list of p-value and fold-change from proDA hdac6proda_submitted.R proDA script hdac6proda_submitted.RData proDA workspace environment, PXD039880 - the raw data is also uploaded to PRIDE.

25 pages, 10 figures, 7 tables.-- This work is distributed under the Creative Commons Attribution 4.0 License, The Global Ocean Data Analysis Project (GLODAP) is a synthesis effort providing regular compilations of surface-to-bottom ocean biogeochemical bottle data, with an emphasis on seawater inorganic carbon chemistry and related variables determined through chemical analysis of seawater samples. GLODAPv2.2021 is an update of the previous version, GLODAPv2.2020 (Olsen et al., 2020). The major changes are as follows: data from 43 new cruises were added, data coverage was extended until 2020, all data with missing temperatures were removed, and a digital object identifier (DOI) was included for each cruise in the product files. In addition, a number of minor corrections to GLODAPv2.2020 data were performed. GLODAPv2.2021 includes measurements from more than 1.3 million water samples from the global oceans collected on 989 cruises. The data for the 12 GLODAP core variables (salinity, oxygen, nitrate, silicate, phosphate, dissolved inorganic carbon, total alkalinity, pH, CFC-11, CFC-12, CFC-113, and CCl4) have undergone extensive quality control with a focus on systematic evaluation of bias. The data are available in two formats: (i) as submitted by the data originator but updated to World Ocean Circulation Experiment (WOCE) exchange format and (ii) as a merged data product with adjustments applied to minimize bias. For this annual update, adjustments for the 43 new cruises were derived by comparing those data with the data from the 946 quality controlled cruises in the GLODAPv2.2020 data product using crossover analysis. Comparisons to estimates of nutrients and ocean CO2 chemistry based on empirical algorithms provided additional context for adjustment decisions in this version. The adjustments are intended to remove potential biases from errors related to measurement, calibration, and data handling practices without removing known or likely time trends or variations in the variables evaluated. The compiled and adjusted data product is believed to be consistent with to better than 0.005 in salinity, 1% in oxygen, 2% in nitrate, 2% in silicate, 2% in phosphate, 4 μmolkg-1 in dissolved inorganic carbon, 4 μmolkg-1 in total alkalinity, 0.01–0.02 in pH (depending on region), and 5% in the halogenated transient tracers. The other variables included in the compilation, such as isotopic tracers and discrete CO2 fugacity (fCO2), were not subjected to bias comparison or adjustments., The original data, their documentation, and DOI codes are available at the Ocean Carbon Data System of NOAA NCEI (https://www.ncei.noaa.gov/access/ocean-carbon-data-system/oceans/GLODAPv2_2021/, last access: 7 July 2021). This site also provides access to the merged data product, which is provided as a single global file and as four regional ones – the Arctic, Atlantic, Indian, and Pacific oceans – under https://doi.org/10.25921/ttgq-n825 (Lauvset et al., 2021). These bias-adjusted product files also include significant ancillary and approximated data and can be accessed via https://www.glodap.info (last access: 29 June 2021). These were obtained by interpolation of, or calculation from, measured data. This living data update documents the GLODAPv2.2021 methods and provides a broad overview of the secondary quality control procedures and results, This research has been supported by EU Horizon 2020 through the EuroSea action (grant no. 862626), internal strategic funding from NORCE Climate, Prociencia/UERJ (grant 2019–2021), IEO RADIALES and RADPROF projects, the UK Climate Linked Atlantic Sector Science (CLASS) NERC National Capability Long-term Single Centre Science Programme(grant no. NE/R015953/1), the BOCATS2 (PID2019-104279GBC21) project funded by MCIN/AEI/10.13039/501100011033 and contributing toWATER:iOS CSIC PTI, the NOAA Global Observations and Monitoring Division (fund reference 100007298), the Office of Oceanic and Atmospheric Research of NOAA Global Observations and Monitoring Division (fund reference 100007298), the Office of Oceanic and Atmospheric Research of NOAA, the BONUS INTEGRAL project (grant no. 03F0773A), the Australian Antarctic Program Partnership and the Integrated Marine Observing System, EU Horizon 2020 action SO-CHIC (grant no. 821001), and the Initiative and Networking Fund of the Helmholtz Association through the project “Digital Earth” (grant no. ZT-0025)

Target 2035, an international federation of biomedical scientists from the public and private sectors, is leveraging ‘open’ principles to develop a pharmacological tool for every human protein.

The ocean absorbs approximately a quarter of the carbon dioxide currently released to the atmosphere by human activities (Canth). A disproportionately large fraction accumulates in the North Atlantic due to the combined effects of transport by the Atlantic Meridional Overturning Circulation (AMOC) and air–sea exchange. However, discrepancies exist between modelled and observed estimates of the air–sea exchange due to unresolved ocean transport variability. Here we quantify the strength and variability of Canth transports across 26.5° N in the North Atlantic between 2004 and 2012 using circulation measurements from the RAPID mooring array and hydrographic observations. Over this period, decreasing circulation strength tended to decrease northward Canth transport, while increasing Canth concentrations (preferentially in the upper limb of the overturning circulation) tended to increase northward Canth transport. These two processes compensated each other over the 8.5-year period. While ocean transport and air–sea Canth fluxes are approximately equal in magnitude, the increasing accumulation rate of Canth in the North Atlantic combined with a stable ocean transport supply means we infer a growing contribution from air–sea Canth fluxes over the period. North Atlantic Canth accumulation is thus sensitive to AMOC strength, but growing atmospheric Canth uptake continues to significantly impact Canth transports. Slowdown of the Atlantic Meridional Overturning Circulation from 2004 to 2012 led to a decrease in its relative contribution to North Atlantic carbon accumulation, while the supply from air–sea fluxes increased, according to an analysis of ocean mooring circulation observations.

We present optical and ultraviolet photometry, as well as optical spectra, for the type II supernova (SN) 2015bf. Our observations cover the phases from ∼2 to ∼200 d after explosion. The first spectrum is characterized by a blue continuum with a blackbody temperature of ∼24 000 K and flash-ionized emission lines. After about 1 week, the spectra of SN 2015bf evolve like those of a regular SN II. From the luminosity of the narrow emission component of H α, we deduce that the mass-loss rate is larger than ${\sim}3.7\times 10^{-3}\, {\rm M_\odot \, yr^{-1}}$. The disappearance of the flash features in the first week after explosion indicates that the circumstellar material is confined within ∼6 × 1014 cm. Thus, we suggest that the progenitor of SN 2015bf experienced violent mass loss shortly before the supernova explosion. The multiband light curves show that SN 2015bf has a high peak luminosity with an absolute visual magnitude MV = −18.11 ± 0.08 mag and a fast post-peak decline with a V-band decay of 1.22 ± 0.09 mag within ∼50 d after maximum light. Moreover, the R-band tail luminosity of SN 2015bf is fainter than that of SNe II with similar peak by 1–2 mag, suggesting a small amount of 56Ni (${\sim}0.009\, {\rm M_\odot }$) synthesized during the explosion. Such a low nickel mass indicates that the progenitor of SN 2015bf could be a super-asymptotic-giant-branch star that collapsed owing to electron capture.

When discovered, SN~2017egm was the closest (redshift $z=0.03$) hydrogen-poor superluminous supernova (SLSN-I) and a rare case that exploded in a massive and metal-rich galaxy. Thus, it has since been extensively observed and studied. We report spectroscopic data showing strong emission at around He~I $\lambda$10,830 and four He~I absorption lines in the optical. Consequently, we classify SN~2017egm as a member of an emerging population of helium-rich SLSNe-I (i.e., SLSNe-Ib). We also present our late-time photometric observations. By combining them with archival data, we analyze high-cadence ultra-violet, optical, and near-infrared light curves spanning from early pre-peak ($\sim -20\,d$) to late phases ($\sim +300\,d$). We obtain its most complete bolometric light curve, in which multiple bumps are identified. None of the previously proposed models can satisfactorily explain all main light-curve features, while multiple interactions between the ejecta and circumstellar material (CSM) may explain the undulating features. The prominent infrared excess with a blackbody luminosity of $10^7$--$10^8\,L_{sun}$ detected in SN~2017egm could originate from the emission of either an echo of a pre-existing dust shell, or newly-formed dust, offering an additional piece of evidence supporting the ejecta-CSM interaction model. Moreover, our analysis of deep $Chandra$ observations yields the tightest-ever constraint on the X-ray emission of an SLSN-I, amounting to an X-ray-to-optical luminosity ratio $\lesssim 10^{-3}$ at late phases ($\sim100-200\,d$), which could help explore its close environment and central engine., Comment: 25 pages, 14 Figures, 4 Tables; accepted for publication in ApJ (Mar. 2023)

In addition to reducing carbon dioxide (CO2) emissions, actively removing CO2 from the atmosphere is widely considered necessary to keep global warming well below 2°C. Ocean Alkalinity Enhancement (OAE) describes a suite of such CO2 removal processes that all involve enhancing the buffering capacity of seawater. In theory, OAE both stores carbon and offsets ocean acidification. In practice, the response of the marine biogeochemical system to OAE must be demonstrably negligible, or at least manageable, before it can be deployed at scale. We tested the OAE response of two natural seawater mixed layer microbial communities in the North Atlantic Subtropical Gyre, one at the Western gyre boundary, and one in the middle of the gyre. We conducted 4-day microcosm incubation experiments at sea, spiked with three increasing amounts of alkaline sodium salts and a 13C-bicarbonate tracer at constant pCO2. We then measured a suite of dissolved and particulate parameters to constrain the chemical and biological response to these additions. Microbial communities demonstrated occasionally measurable, but mostly negligible, responses to alkalinity enhancement. Neither site showed a significant increase in biologically produced CaCO3, even at extreme alkalinity loadings of +2,000 μmol kg−1. At the gyre boundary, alkalinity enhancement did not significantly impact net primary production rates. In contrast, net primary production in the central gyre decreased by ~30% in response to alkalinity enhancement. The central gyre incubations demonstrated a shift toward smaller particle size classes, suggesting that OAE may impact community composition and/or aggregation/disaggregation processes. In terms of chemical effects, we identify equilibration of seawater pCO2, inorganic CaCO3 precipitation, and immediate effects during mixing of alkaline solutions with seawater, as important considerations for developing experimental OAE methodologies, and for practical OAE deployment. These initial results underscore the importance of performing more studies of OAE in diverse marine environments, and the need to investigate the coupling between OAE, inorganic processes, and microbial community composition.

Survival of motor neuron (SMN) functions in diverse biological pathways via recognition of symmetric dimethylarginine (Rme2s) on proteins by its Tudor domain, and deficiency of SMN leads to spinal muscular atrophy. Here we report a potent and selective antagonist with a 4-iminopyridine scaffold targeting the Tudor domain of SMN. Our structural and mutagenesis studies indicate that both the aromatic ring and imino groups of compound 1 contribute to its selective binding to SMN. Various on-target engagement assays support that compound 1 specifically recognizes SMN in a cellular context and prevents the interaction of SMN with the R1810me2s of RNA polymerase II subunit POLR2A, resulting in transcription termination and R-loop accumulation mimicking SMN depletion. Thus, in addition to the antisense, RNAi and CRISPR/Cas9 techniques, potent SMN antagonists could be used as an efficient tool to understand the biological functions of SMN.

Ni, Y. Q., et al., Type Ia supernovae are thermonuclear explosions of white dwarf stars. They play a central role in the chemical evolution of the Universe and are an important measure of cosmological distances. However, outstanding questions remain about their origins. Despite extensive efforts to obtain natal information from their earliest signals, observations have thus far failed to identify how the majority of them explode. Here, we present infant-phase detections of SN 2018aoz from a very low brightness of −10.5 AB absolute magnitude, revealing a hitherto unseen plateau in the B band that results in a rapid redward colour evolution between 1.0 and 12.4 hours after the estimated epoch of first light. The missing B-band flux is best explained by line-blanket absorption from Fe-peak elements in the outer 1% of the ejected mass. The observed B − V colour evolution of the supernova also matches the prediction from an over-density of Fe-peak elements in the same outer 1% of the ejected mass, whereas bluer colours are expected from a purely monotonic distribution of Fe-peak elements. The presence of excess nucleosynthetic material in the extreme outer layers of the ejecta points to enhanced surface nuclear burning or extended subsonic mixing processes in some normal type Ia SN explosions., D.-S.M., M.R.D. and C.D.M. are supported by Discovery Grants from the Natural Sciences and Engineering Research Council of Canada. D.-S.M. was supported in part by a Leading Edge Fund from the Canadian Foundation for Innovation (project no. 30951). M.R.D. was supported in part by the Canada Research Chairs Program, the Canadian Institute for Advanced Research (CIFAR) and the Dunlap Institute at the University of Toronto. D.J.S. acknowledges support by NSF grant nos. AST-1821987, 1821967 and 1908972 and from the Heising–Simons Foundation under grant no. 2020-1864. S.G.-G. acknowledges support by FCT under project CRISP PTDC/FIS-AST-31546 and project UIDB/00099/2020. H.S.P. was supported in part by a National Research Foundation (NRF) of Korea grant funded by the Korean government (MSIT, Ministry of Science and ICT; no. NRF-2019R1F1A1058228). P.J.B. acknowledges support from the Swift GI program 80NSSC19K0316. S.V., Y.D. and K.A.B. acknowledge support by NSF grant nos. AST-1813176 and AST-2008108. C.M. acknowledges support by NSF grant AST-1313484. I.A. is a CIFAR Azrieli Global Scholar in the Gravity and the Extreme Universe Program and acknowledges support from that program, from the Israel Science Foundation (grant nos. 2108/18 and 2752/19), from the United States – Israel Binational Science Foundation (BSF) and from an Israeli Council for Higher Education Alon Fellowship. R.L.B. acknowledges support by NASA through Hubble Fellowship grant no. 51386.01 awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA under contract no. NAS 5-26555. A.G.-Y. acknowledges support from the European Union via ERC grant no. 725161, the ISF GW Excellence Center, an IMOS space infrastructure grant and BSF/Transformative and GIF grants, as well as from the Benoziyo Endowment Fund for the Advancement of Science, the Deloro Institute for Advanced Research in Space and Optics, the Veronika A. Rabl Physics Discretionary Fund, P. and T. Gardner, the Yeda-Sela Center for Basic Research and a WIS-CIT joint research grant. A.G.-Y. is the recipient of the Helen and Martin Kimmel Award for Innovative Investigation. L.G. acknowledges financial support from the Spanish Ministerio de Ciencia e Innovación (MCIN), the Agencia Estatal de Investigación (AEI) 10.13039/501100011033, the European Social Fund (ESF) ‘Investing in your future’ under the 2019 Ramón y Cajal program RYC2019-027683-I and the PID2020-115253GA-I00 HOSTFLOWS project, as well as from the Centro Superior de Investigaciones Científicas (CSIC) under the PIE project 20215AT016. G.P. acknowledges support from the Millennium Science Initiative through grant no. IC120009. J.A. is supported by the Stavros Niarchos Foundation (SNF) and the Hellenic Foundation for Research and Innovation (HFRI) under the 2nd Call of ‘Science and Society’ Action ‘Always strive for excellence – Theodoros Papazoglou’ (project no. 01431).