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Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1–3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.

Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1–3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the JamesWebb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.

Over the past 50 years, prominent mid-infrared (MIR) emission features from 3–20 µm have been observed ubiquitously in the interstellar medium (ISM) of Galactic and extragalactic sources. These emission features arise from the vibrational relaxation of polycyclic aromatic hydrocarbons (PAHs) after the absorption of a far-ultraviolet (FUV) photon. PAHs are astronomically significant in that they contain up to 15% of the cosmic carbon inventory and play an important role in the physical and chemical processes of the ISM such as, for example, the gas heating and the ionization balance. Variations in the relative strengths of the major PAH bands can be used to understand their underlying molecular properties and their interaction with the surrounding photodissociation region (PDR) environment.We employ these variations to characterize the PAH populations in terms of properties such as degree of ionization and sizes and investigate their dependence on the physical conditions such as the FUV radiation field strength, the gas density and the gas temperature for nearby spatially resolved Galactic PDRs. We find both size and charge tend to rise with increasing radiation field strength or proximity to the illuminating source. Correlations between PAH emission features in spatially resolved sources are found to be highly dependent on the PDR morphology (i.e. edge-on versus face-on) and environmental conditions. These results are indicative of significant UV processing driving the photochemical evolution of astronomical PAH populations.We utilize observations of far-infrared (FIR) cooling lines of atoms and the FIR dust continuum emission of a nearby reflection nebula in combination with PDR models to derive maps of the physical conditions. Comparing these derived physical conditions with PAH emission characteristics at a matching spatial resolution and apertures allows us to critically test previous established relationships between PAH emission and these physical conditions. From these results, we show that these relationships also hold at a higher spatial resolution than previously obtained.

We use the measured fluxes of polycyclic aromatic hydrocarbon (PAH) emission features at 6.2, 7.7, 8.6, 11.0 and 11.2 \\(\\mu\\)m in the reflection nebula NGC 2023 to carry out a principal component analysis (PCA) as a means to study previously reported variations in the PAH emission. We find that almost all of the variations (99%) can be explained with just two parameters -- the first two principal components (PCs). We explore the characteristics of these PCs and show that the first PC (\\(PC_{1}\\)), which is the primary driver of the variation, represents the amount of emission of a mixture of PAHs with ionized species dominating over neutral species. The second PC (\\(PC_{2}\\)) traces variations in the ionization state of the PAHs across the nebula. Correlations of the PCs with various PAH ratios show that the 6.2 and 7.7 \\(\\mu\\)m bands behave differently than the 8.6 and 11.0 \\(\\mu\\)m bands, thereby forming two distinct groups of ionized bands. We compare the spatial distribution of the PCs to the physical conditions, in particular to the strength of the radiation field, \\(G_{0}\\), and the \\(G_{0}/n_{H}\\) ratio and find that the variations in \\(PC_{2}\\), i.e. the ionization state of PAHs are strongly affected by \\(G_{0}\\) whereas the amount of PAH emission (as traced by \\(PC_{1}\\)) does not depend on \\(G_0\\).

Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the Universe, from the era of vigorous star formation at redshifts of 1-3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template datasets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template datasets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photo-dissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, impacting planet formation within the disks. We report JWST and Atacama Large Millimetere Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modelling their kinematics and excitation allows us to constrain the physical conditions within the gas. We quantify the mass-loss rate induced by the FUV irradiation, finding it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk.

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid α-synuclein (αSyn), we reveal that colonization with curli-producing Escherichia coli promotes αSyn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate αSyn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate αSyn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate αSyn aggregation and disease in the gut and the brain.

Amyloids are a class of protein with unique self-aggregation properties, and their aberrant accumulation can lead to cellular dysfunctions associated with neurodegenerative diseases. While genetic and environmental factors can influence amyloid formation, molecular triggers and/or facilitators are not well defined. Growing evidence suggests that non-identical amyloid proteins may accelerate reciprocal amyloid aggregation in a prion-like fashion. While humans encode ~30 amyloidogenic proteins, the gut microbiome also produces functional amyloids. For example, curli are cell surface amyloid proteins abundantly expressed by certain gut bacteria. In mice overexpressing the human amyloid [alpha]-synuclein ([alpha]Syn), we reveal that colonization with curli-producing Escherichia coli promotes [alpha]Syn pathology in the gut and the brain. Curli expression is required for E. coli to exacerbate [alpha]Syn-induced behavioral deficits, including intestinal and motor impairments. Purified curli subunits accelerate [alpha]Syn aggregation in biochemical assays, while oral treatment of mice with a gut-restricted amyloid inhibitor prevents curli-mediated acceleration of pathology and behavioral abnormalities. We propose that exposure to microbial amyloids in the gastrointestinal tract can accelerate [alpha]Syn aggregation and disease in the gut and the brain.

Polypharmacy of psychotropic medications predisposes older adults to adverse drug events (ADEs). One contributing factor is inhibition of metabolic pathways between substrates (competitive inhibition) or between substrates and inhibitors of the same cytochrome P450 (CYP450) isoforms. The purpose of this case report is to demonstrate observed sedation and difficulty concentrating from augmentation therapy for resistant major depressive disorder (MDD) and to highlight the value of clinical tools to identify opportunities for treatment optimization to reduce ADEs. The pharmacist identified significant medication burden and competitive inhibition of drug metabolism in the CYP450 system during a telehealth medication therapy management consultation with a 69-year-old male. The pharmacist recommended clinical monitoring and communicated concerns about medication-induced sedation, difficulty concentrating, and other medication-related problems (MRP) to providers. Several recommendations were implemented which helped improved patient’s outcomes. Individualizing MDD pharmacotherapy based on pharmacokinetic and pharmacodynamic drug interactions and geriatric dosage considerations may lead to better outcomes and tolerability among older adults.

The discovery of the first interstellar object passing through the Solar System, 1I/2017 U1 (‘Oumuamua), provoked intense and continuing interest from the scientific community and the general public. The faintness of ‘Oumuamua, together with the limited time window within which observations were possible, constrained the information available on its dynamics and physical state. Here we review our knowledge and find that in all cases, the observations are consistent with a purely natural origin for ‘Oumuamua. We discuss how the observed characteristics of ‘Oumuamua are explained by our extensive knowledge of natural minor bodies in our Solar System and our current knowledge of the evolution of planetary systems. We highlight several areas requiring further investigation.‘Oumuamua is the first interstellar interloper observed in our Solar System and studied in some detail. This Perspective reviews the data acquired during its visit and discusses its origin and properties, concluding that there is no basis to the theory of an artificial ‘Oumuamua.