Donated chemical probes for open science

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project

Radio continuum and X-ray emission from the most extreme far-IR-excess galaxy NGC 1377: An extremely obscured AGN revealed

Context. Galaxies which strongly deviate from the radio-far infrared (FIR) correlation are of great importance for studies of galaxy evolution as they may be tracing early, short-lived stages of starbursts and active galactic nuclei (AGNs). The most extreme FIR-excess galaxy NGC 1377 has long been interpreted as a young dusty starburst, but millimeter observations of CO lines revealed a powerful collimated molecular outflow which cannot be explained by star formation alone. Aims. This paper aims to determine the nature of the energy source in the nucleus of NGC 1377 and to study the driving mechanism of the collimated CO outflow. Methods. We present new radio observations of NGC 1377 at 1.5 and 10 GHz obtained with the Jansky Very Large Array (JVLA) and Chandra X-ray observations. The observations are compared to synthetic starburst models to constrain the properties of the central energy source. Results. We obtained the first detection of the cm radio continuum and X-ray emission in NGC 1377. We found that the radio emission is distributed in two components, one on the nucleus and another offset by 4?5 to the south-west. We confirm the extreme FIR-excess of the galaxy, with a qFIR ? 4.2, which deviates by more than 7? from the radio-FIR correlation. Soft X-ray emission is detected on the off-nucleus component. From the radio emission we estimated for a young (<10 Myr) starburst a star formation rate (SFR) of <0.1 M? yr-1. Such a SFR is not sufficient to power the observed IR luminosity and to drive the CO outflow. Conclusions. We found that a young starburst cannot reproduce all the observed properties of the nucleus of NGC 1377. We suggest that the galaxy may be harboring a radio-quiet, obscured AGN of 106M?, accreting at near-Eddington rates. We speculate that the off-nucleus component may be tracing an hot-spot in the AGN jet

Towards the prediction of molecular parameters from astronomical emission lines using Neural Networks

Molecular astronomy is a field that is blooming in the era of large observatories such as the Atacama Large Millimeter/Submillimeter Array (ALMA). With modern, sensitive, and high spectral resolution radio telescopes like ALMA and the Square Kilometer Array, the size of the data cubes is rapidly escalating, generating a need for powerful automatic analysis tools. This work introduces MolPred, a pilot study to perform predictions of molecular parameters such as excitation temperature (T) and column density (log(N)) from input spectra by the use of neural networks. We used as test cases the spectra of CO, HCO, SiO and CHCN between 80 and 400 GHz. Training spectra were generated with MADCUBA, a state-of-the-art spectral analysis tool. Our algorithm was designed to allow the generation of predictions for multiple molecules in parallel. Using neural networks, we can predict the column density and excitation temperature of these molecules with a mean absolute error of 8.5% for CO, 4.1% for HCO, 1.5% for SiO and 1.6% for CHCN. The prediction accuracy depends on the noise level, line saturation, and number of transitions. We performed predictions upon real ALMA data. The values predicted by our neural network for this real data differ by 13% from the MADCUBA values on average. Current limitations of our tool include not considering linewidth, source size, multiple velocity components, and line blending.A.B. wishes to thank Dr. Diego Mardones for his contribution to the early stages of this work. Also, to acknowledge support from the Federico Santa María Technical University General Directorate for Research and Postgraduate Studies (DGIP). JH and SV are funded by the European Research Council (ERC) Advanced Grant MOPPEX 833460. V.M.R. acknowledges support from the Comunidad de Madrid through the Atracción de Talento Investigador Modalidad 1 (Doctores con experiencia) Grant (COOL: Cosmic Origins Of Life; 2019-T1/TIC-15379; PI: V.M. Rivilla)

Starburst Energy Feedback Seen through HCO+/HOC+Emission in NGC 253 from ALCHEMI

Molecular abundances are sensitive to the UV photon flux and cosmic-ray ionization rate. In starburst environments, the effects of high-energy photons and particles are expected to be stronger. We examine these astrochemical signatures through multiple transitions of HCO+ and its metastable isomer HOC+ in the center of the starburst galaxy NGC 253 using data from the Atacama Large Millimeter/submillimeter Array large program ALMA Comprehensive High-resolution Extragalactic Molecular inventory. The distribution of the HOC+(1-0) integrated intensity shows its association with "superbubbles,"cavities created either by supernovae or expanding H ii regions. The observed HCO+/HOC+ abundance ratios are ∼10-150, and the fractional abundance of HOC+ relative to H2 is ∼1.5 × 10-11-6 × 10-10, which implies that the HOC+ abundance in the center of NGC 253 is significantly higher than in quiescent spiral arm dark clouds in the Galaxy and the Galactic center clouds. Comparison with chemical models implies either an interstellar radiation field of G 0 ⪆ 103 if the maximum visual extinction is ⪆5, or a cosmic-ray ionization rate of ζ ⪆ 10-14 s-1 (3-4 orders of magnitude higher than that within clouds in the Galactic spiral arms) to reproduce the observed results. From the difference in formation routes of HOC+, we propose that a low-excitation line of HOC+ traces cosmic-ray dominated regions, while high-excitation lines trace photodissociation regions. Our results suggest that the interstellar medium in the center of NGC 253 is significantly affected by energy input from UV photons and cosmic rays, sources of energy feedback.N.H. acknowledges support from JSPS KAKENHI grant No. JP21K03634. K.S. has been supported by grants MOST 108-2112-M-001-015 and 109- 2112-M-001-020 from the Ministry of Science and Technology, Taiwan. Y.N. is supported by the NAOJ ALMA Scientific Research grant No. 2017-06B. V.M.R. and L.C. are funded by the Comunidad de Madrid through the Atracción de Talento Investigador (Doctores con experiencia) Grant (COOL: Cosmic Origins Of Life; 2019-T1/TIC-15379)

Enzymes for consumer products to achieve climate neutrality

29 pags., 4 figs., 3 tabs., 1 graf.Accumulated greenhouse gas emissions are expected to increase from 36.2 Giga-tons (Gt) to 60 Gt over the next three decades. The global surface temperature has increased by¿+¿1.09¿°C since 2001, and might increase by¿+¿2.2¿°C in 2100, +3.6¿°C in 2200 and +4.6¿°C in 2500. These emissions and temperature rises cannot be reduced in their entirety, but they can be lowered by using enzymes. Enzymes are proteins that catalyze biochemical reactions that make life possible since 3.8 billion years ago. Scientists have been able to "domesticate" them in such a way that enzymes, and their engineered variants, are now key players of the circular economy. With a world production of 117 Kilo-tons and a trade of 14.5 Billion-dollars, they have the potential to annually decrease CO2 emissions by 1 to 2.5 Billion-tons (Bt), the carbon demand to synthesise chemicals by 200 Million tons (Mt), the amount of chemicals by 90¿Mt, and the economic losses derived from global warming by 0.5%, while promoting biodiversity and our planet¿s health. Our success to increase these benefits will depend on better integration of enzymatic solutions in different sectors.This study was conducted under the auspices of the FuturEnzyme Project funded by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 101000327. MF also acknowledges Grants PID2020-112758RB-I00, PDC2021-121534-I00, and TED2021-130544B-I00 from the MCIN/AEI/10.13039/501100011033 and the European Union (“NextGenerationEU/PRTR”)

Conjunctive Visual Processing Appears Abnormal in Autism

Face processing in autism spectrum disorder (ASD) is thought to be atypical, but it is unclear whether differences in visual conjunctive processing are specific to faces. To address this, we adapted a previously established eye-tracking paradigm which modulates the need for conjunctive processing by varying the degree of feature ambiguity in faces and objects. Typically-developed (TD) participants showed a canonical pattern of conjunctive processing: High-ambiguity objects were processed more conjunctively than low-ambiguity objects, and faces were processed in an equally conjunctive manner regardless of ambiguity level. In contrast, autistic individuals did not show differences in conjunctive processing based on stimulus category, providing evidence that atypical visual conjunctive processing in ASD is the result of a domain general lack of perceptual specialization

Effects of Aliskiren on Stroke in Rats Expressing Human Renin and Angiotensinogen Genes

OBJECTIVE: Pre-treatment with angiotensin receptor blockers is known to improve neurological outcome after stroke. This study investigated for the first time, whether the renin inhibitor aliskiren has similar neuroprotective effects. METHODS: Since aliskiren specifically blocks human renin, double transgenic rats expressing human renin and angiotensinogen genes were used. To achieve a systolic blood pressure of 150 or 130 mmHg animals were treated with aliskiren (7.5 or 12.5 mg/kg*d) or candesartan (1.5 or 10 mg/kg*d) via osmotic minipump starting five days before middle cerebral artery occlusion with reperfusion. Infarct size was determined by magnetic resonance imaging. mRNA of inflammatory marker genes was studied in different brain regions. RESULTS: The mortality of 33.3% (7 of 21 animals) in the vehicle group was reduced to below 10% by treatment with candesartan or aliskiren (p<0.05). Aliskiren-treated animals had a better neurological outcome 7 days post-ischemia, compared to candesartan (Garcia scale: 9.9±0.7 vs. 7.3±0.7; p<0.05). The reduction of infarct size in the aliskiren group did not reach statistical significance compared to candesartan and vehicle (24 h post-ischemia: 314±81 vs. 377±70 and 403±70 mm(3) respectively). Only aliskiren was able to significantly reduce stroke-induced gene expression of CXC chemokine ligand 1, interleukin-6 and tumor necrosis factor-alpha in the ischemic core. CONCLUSIONS: Head-to-head comparison suggests that treatment with aliskiren before and during cerebral ischemia is at least as effective as candesartan in double transgenic rats. The improved neurological outcome in the aliskiren group was blood pressure independent. Whether this effect is due to primary anti-inflammatory mechanisms has to be investigated further

GOALS-JWST: Mid-infrared Spectroscopy of the Nucleus of NGC 7469

We present mid-infrared spectroscopic observations of the nucleus of the nearby Seyfert galaxy NGC 7469 taken with the MIRI instrument on the James Webb Space Telescope (JWST) as part of Directors Discretionary Time Early Release Science program 1328. The high-resolution nuclear spectrum contains 19 emission lines covering a wide range of ionization. The high-ionization lines show broad, blueshifted emission reaching velocities up to 1700 km s−1 and FWHM ranging from ∼500 to 1100 km s−1. The width of the broad emission and the broad-to-narrow line flux ratios correlate with ionization potential. The results suggest a decelerating, stratified, AGN-driven outflow emerging from the nucleus. The estimated mass outflow rate is 1-2 orders of magnitude larger than the current black hole accretion rate needed to power the AGN. Eight pure rotational H2 emission lines are detected with intrinsic widths ranging from FWHM ∼125 to 330 km s−1. We estimate a total mass of warm H2 gas of ∼1.2 7 107 M ⊙ in the central 100 pc. The PAH features are extremely weak in the nuclear spectrum, but a 6.2 μm PAH feature with an equivalent width of ∼0.07 μm and a flux of 2.7 7 10−17 W m−2 is detected. The spectrum is steeply rising in the mid-infrared, with a silicate strength of ∼0.02, significantly smaller than seen in most PG QSOs but comparable to other Seyfert 1s. These early MIRI mid-infrared IFU data highlight the power of JWST to probe the multiphase interstellar media surrounding actively accreting supermassive black holes

GOALS-JWST: Resolving the Circumnuclear Gas Dynamics in NGC 7469 in the Mid-infrared

The nearby, luminous infrared galaxy NGC 7469 hosts a Seyfert nucleus with a circumnuclear star-forming ring and is thus the ideal local laboratory for investigating the starburst-AGN (active galactic nucleus) connection in detail. We present integral-field observations of the central 1.3 kpc region in NGC 7469 obtained with the JWST Mid-InfraRed Instrument. Molecular and ionized gas distributions and kinematics at a resolution of ∼100 pc over the 4.9-7.6 μm region are examined to study the gas dynamics influenced by the central AGN. The low-ionization [Fe ii] λ5.34 μm and [Ar ii] λ6.99 μm lines are bright on the nucleus and in the starburst ring, as opposed to H2 S(5) λ6.91 μm, which is strongly peaked at the center and surrounding ISM. The high-ionization [Mg v] line is resolved and shows a broad, blueshifted component associated with the outflow. It has a nearly face-on geometry that is strongly peaked on the nucleus, where it reaches a maximum velocity of −650 km s−1, and extends about 400 pc to the east. Regions of enhanced velocity dispersion in H2 and [Fe ii] ∼ 180 pc from the AGN that also show high L(H2)/L(PAH) and L([Fe ii])/L(Pfα) ratios to the W and N of the nucleus pinpoint regions where the ionized outflow is depositing energy, via shocks, into the dense interstellar medium between the nucleus and the starburst ring. These resolved mid-infrared observations of the nuclear gas dynamics demonstrate the power of JWST and its high-sensitivity integral-field spectroscopic capability to resolve feedback processes around supermassive black holes in the dusty cores of nearby luminous infrared galaxies

GOALS-JWST: Small neutral grains and enhanced 3.3 micron PAH emission in the Seyfert galaxy NGC 7469

We present James Webb Space Telescope (JWST) Near Infrared Spectrograph (NIRSpec) integral-field spectroscopy of the nearby luminous infrared galaxy, NGC 7469. We take advantage of the high spatial/spectral resolution and wavelength coverage of JWST /NIRSpec to study the 3.3 um neutral polycyclic aromatic hydrocarbon (PAH) grain emission on ~60 pc scales. We find a clear change in the average grain properties between the star-forming ring and the central AGN. Regions in the vicinity of the AGN, with [NeIII]/[NeII]>0.25, tend to have larger grain sizes and lower aliphatic-to-aromatic (3.4/3.3) ratios indicating that smaller grains are preferentially removed by photo-destruction in the vicinity of the AGN. We find an overall suppression of the total PAH emission relative to the ionized gas in the central 1 kpc region of the AGN in NGC 7469 compared to what has been observed with Spitzer on 3 kpc scales. However, the fractional 3.3 um to total PAH power is enhanced in the starburst ring, possibly due to a variety of physical effects on sub-kpc scales, including recurrent fluorescence of small grains or multiple photon absorption by large grains. Finally, the IFU data show that while the 3.3 um PAH-derived star formation rate (SFR) in the ring is 8% higher than that inferred from the [NeII] and [NeIII] emission lines, the integrated SFR derived from the 3.3 um feature would be underestimated by a factor of two due to the deficit of PAHs around the AGN, as might occur if a composite system like NGC 7469 were to be observed at high-redshift.Comment: 14 pages, 5 figures, 2 tables, Submitted to ApJ