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| 2. |
- Bakken, TE, et al.
(författare)
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Comparative cellular analysis of motor cortex in human, marmoset and mouse
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 111-
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Tidskriftsartikel (refereegranskat)abstract
- The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.
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| 3. |
- Murawski, Christopher D., et al.
(författare)
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Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
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Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
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Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
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| 4. |
- Schluter, J., et al.
(författare)
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The gut microbiota is associated with immune cell dynamics in humans
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 588:7837, s. 303-307
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Tidskriftsartikel (refereegranskat)abstract
- Influence of the gut microbiome on the human immune system is revealed by systems analysis of vast clinical data from decades of electronic health records paired with massive longitudinal microbiome sequencing. The gut microbiota influences development(1-3) and homeostasis(4-7) of the mammalian immune system, and is associated with human inflammatory(8) and immune diseases(9,10) as well as responses to immunotherapy(11-14). Nevertheless, our understanding of how gut bacteria modulate the immune system remains limited, particularly in humans, where the difficulty of direct experimentation makes inference challenging. Here we study hundreds of hospitalized-and closely monitored-patients with cancer receiving haematopoietic cell transplantation as they recover from chemotherapy and stem-cell engraftment. This aggressive treatment causes large shifts in both circulatory immune cell and microbiota populations, enabling the relationships between the two to be studied simultaneously. Analysis of observed daily changes in circulating neutrophil, lymphocyte and monocyte counts and more than 10,000 longitudinal microbiota samples revealed consistent associations between gut bacteria and immune cell dynamics. High-resolution clinical metadata and Bayesian inference allowed us to compare the effects of bacterial genera in relation to those of immunomodulatory medications, revealing a considerable influence of the gut microbiota-together and over time-on systemic immune cell dynamics. Our analysis establishes and quantifies the link between the gut microbiota and the human immune system, with implications for microbiota-driven modulation of immunity.
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| 5. |
- King, Matthew R., et al.
(författare)
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Macromolecular condensation organizes nucleolar sub-phases to set up a pH gradient
- 2024
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 187:8, s. 24-1889
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Tidskriftsartikel (refereegranskat)abstract
- Nucleoli are multicomponent condensates defined by coexisting sub-phases. We identified distinct intrinsically disordered regions (IDRs), including acidic (D/E) tracts and K-blocks interspersed by E-rich regions, as defining features of nucleolar proteins. We show that the localization preferences of nucleolar proteins are determined by their IDRs and the types of RNA or DNA binding domains they encompass. In vitro reconstitutions and studies in cells showed how condensation, which combines binding and complex coacervation of nucleolar components, contributes to nucleolar organization. D/E tracts of nucleolar proteins contribute to lowering the pH of co-condensates formed with nucleolar RNAs in vitro. In cells, this sets up a pH gradient between nucleoli and the nucleoplasm. By contrast, juxta-nucleolar bodies, which have different macromolecular compositions, featuring protein IDRs with very different charge profiles, have pH values that are equivalent to or higher than the nucleoplasm. Our findings show that distinct compositional specificities generate distinct physicochemical properties for condensates.
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| 6. |
- Rocha, W. R.M., et al.
(författare)
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JWST Observations of Young protoStars (JOYS+): Detecting icy complex organic molecules and ions: I. CH4, SO2, HCOO, OCN, H2CO, HCOOH, CH3CH2OH, CH3CHO, CH3OCHO, and CH3COOH
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 683
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Tidskriftsartikel (refereegranskat)abstract
- Context. Complex organic molecules (COMs) are ubiquitously detected in the gas phase and thought to be mostly formed on icy grains. Nevertheless, there have not been any unambiguous detections of COMs larger than CH3OH in ices reported thus far. Exploring this matter in greater detail has now become possible with the unprecedented possibilities offered by the James Webb Space Telescope (JWST) within the infrared (IR) spectral range with its very high sensitivity and spectral resolution in the critical 5 10 μm range, the fingerprint region of oxygen-bearing COMs. Aims. In the JWST Observations of Young protoStars (JOYS+) program, more than 30 protostars are undergoing observation with the Medium Resolution Spectrograph (MRS) of the Mid-IR Instrument (MIRI). The goal of this study is to comprehensively explore the COMs ice signatures in one low- and one high-mass protostar: NGC 1333 IRAS 2A and IRAS 23385+6053, respectively. Methods. We performed global continuum and silicate subtractions of the MIRI-MRS spectra, followed by a local continuum subtraction in optical depth scale in the range around 6.8 and 8.6 μm, the ice COM fingerprint region. We explored different choices for the local continuum and silicate subtraction. Next, we fit the observational data with a large sample of available IR laboratory ice spectra. We used the ENIIGMA fitting tool, a genetic algorithm-based code that not only finds the best fit between the lab data and the observations, but also performs a statistical analysis of the solutions, such as deriving the confidence intervals and quantifying fit degeneracy. Results. We report the best fits for the spectral ranges between 6.8 and 8.6 μm in NGC 1333 IRAS 2A and IRAS 23385+6053, originating from simple molecules and COMs, as well as negative ions. Overall, we find that ten chemical species are needed to reproduce the astronomical data. The strongest feature in this range (7.7 μm) is dominated by CH4, with contributions from SO2 and OCN. Our results indicate that the 7.2 and 7.4 μm bands are mostly dominated by HCOO. We also find statistically robust detections of COMs based on multiple bands, most notably, CH3CHO, CH3CH2OH, and CH3OCHO. We also report a likely detection of CH3COOH. Based on the ice column density ratios between CH3CH2OH and CH3CHO of NGC 1333 IRAS 2A and IRAS 23385+6053, we find compelling evidence that these COMs are formed on icy grains. Finally, the derived ice abundances for NGC 1333 IRAS 2A correlate well with those in comet 67P/GC within a factor of 5. Conclusions. Based on the high-quality JWST (MIRI-MRS) spectra, we conclude that COMs are present in interstellar ices, thus providing additional proof for the solid-state origin of these species in star-forming regions. In addition, the good correlation between the ice abundances in comet 67P and NGC 1333 IRAS 2A is fully in line with the idea that cometary COMs may be inherited from the early protostellar phases to a significant extent.
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| 7. |
- Van Gelder, M. L., et al.
(författare)
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JOYS+: Mid-infrared detection of gas-phase SO 2 emission in a low-mass protostar
- 2024
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Tidskriftsartikel (refereegranskat)abstract
- Context. Thanks to the Mid-InfraRed Instrument (MIRI) on the James Webb Space Telescope (JWST), our ability to observe the star formation process in the infrared has greatly improved. Due to its unprecedented spatial and spectral resolution and sensitivity in the mid-infrared, JWST/MIRI can see through highly extincted protostellar envelopes and probe the warm inner regions. An abundant molecule in these warm inner regions is SO2, which is a common tracer of both outflow and accretion shocks as well as hot core chemistry. Aims. This paper presents the first mid-infrared detection of gaseous SO2 emission in an embedded low-mass protostellar system rich in complex molecules and aims to determine the physical origin of the SO2 emission. Methods. JWST/MIRI observations taken with the Medium Resolution Spectrometer (MRS) of the low-mass protostellar binary NGC 1333 IRAS 2A in the JWST Observations of Young protoStars (JOYS+) program are presented. The observations reveal emission from the SO2 ν3 asymmetric stretching mode at 7.35 µm. Using simple slab models and assuming local thermodynamic equilibrium (LTE), we derived the rotational temperature and total number of SO2 molecules. We then compared the results to those derived from high-angular-resolution SO2 data on the same scales (∼50−100 au) obtained with the Atacama Large Millimeter/submillimeter Array (ALMA). Results. The SO2 emission from the ν3 band is predominantly located on ∼50−100 au scales around the mid-infrared continuum peak of the main component of the binary, IRAS 2A1. A rotational temperature of 92 ± 8 K is derived from the ν3 lines. This is in good agreement with the rotational temperature derived from pure rotational lines in the vibrational ground state (i.e., ν = 0) with ALMA (104 ± 5 K), which are extended over similar scales. However, the emission of the ν3 lines in the MIRI-MRS spectrum is not in LTE given that the total number of molecules predicted by a LTE model is found to be a factor of 2 × 104 higher than what is derived for the ν = 0 state from the ALMA data. This difference can be explained by a vibrational temperature that is ∼100 K higher than the derived rotational temperature of the ν = 0 state: Tvib ∼ 200 K versus Trot = 104 ± 5 K. The brightness temperature derived from the continuum around the ν3 band (∼7.35 µm) of SO2 is ∼180 K, which confirms that the ν3 = 1 level is not collisionally populated but rather infrared-pumped by scattered radiation. This is also consistent with the non-detection of the ν2 bending mode at 18−20 µm. The similar rotational temperature derived from the MIRI-MRS and ALMA data implies that they are in fact tracing the same molecular gas. The inferred abundance of SO2 , determined using the LTE fit to the lines of the vibrational ground state in the ALMA data, is 1.0 ± 0.3 × 10−8 with respect to H2, which is on the lower side compared to interstellar and cometary ices (10−8−10−7). Conclusions. Given the rotational temperature, the extent of the emission (∼100 au in radius), and the narrow line widths in the ALMA data (∼3.5 km s−1), the SO2 in IRAS 2A likely originates from ice sublimation in the central hot core around the protostar rather than from an accretion shock at the disk–envelope boundary. Furthermore, this paper shows the importance of radiative pumping and of combining JWST observations with those from millimeter interferometers such as ALMA to probe the physics on disk scales and to infer molecular abundances.
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