Abstract
In this paper, we model the chemical evolution of a 0.25 M⊙ protoplanetary disc surrounding a 1 M⊙ star that undergoes fragmentation due to self-gravity. We use smoothed particle ...hydrodynamics including a radiative transfer scheme, along with a time-dependent chemical evolution code to follow the composition of the disc and resulting fragments over approximately 4000 yr. Initially, four quasi-stable fragments are formed, of which two are eventually disrupted by tidal torques in the disc. From the results of our chemical modelling, we identify species that are abundant in the fragments (e.g. H2O, H2S, HNO, N2, NH3, OCS, SO), species that are abundant in the spiral shocks within the disc (e.g. CO, CH4, CN, CS, H2CO) and species that are abundant in the circumfragmentary material (e.g. HCO+). Our models suggest that in some fragments it is plausible for grains to sediment to the core before releasing their volatiles into the planetary envelope, leading to changes in, e.g., the C/O ratio of the gas and ice components. We would therefore predict that the atmospheric composition of planets generated by gravitational instability should not necessarily follow the bulk chemical composition of the local disc material.
An iron-tetraphenylcyclopentadienone tricarbonyl complex is demonstrated to act as a precursor of a catalyst for the formation of C–N bonds through a “hydrogen-borrowing” reaction between amines and ...alcohols.
ABSTRACT The chemistry of H2O, CO, and other small molecular species in an isolated pre-stellar core, L1544, has been assessed in the context of a comprehensive gas-grain chemical model, coupled to ...an empirically constrained physical/dynamical model. Our main findings are (i) that the chemical network remains in near equilibrium as the core evolves towards star formation and the molecular abundances change in response to the evolving physical conditions. The gas-phase abundances at any time can be calculated accurately with equilibrium chemistry, and the concept of chemical clocks is meaningless in molecular clouds with similar conditions and dynamical time-scales, and (ii) A comparison of the results of complex and simple chemical networks indicates that the abundances of the dominant oxygen and carbon species, H2O, CO, C, and C+ are reasonably approximated by simple networks. In chemical equilibrium, the time-dependent differential terms vanish, and a simple network reduces to a few algebraic equations. This allows rapid calculation of the abundances most responsible for spectral line radiative cooling in molecular clouds with long dynamical time-scales. The dust ice mantles are highly structured and the ice layers retain a memory of the gas-phase abundances at the time of their deposition. A complex (gas-phase and gas-grain) chemical structure therefore exists, with cosmic-ray induced processes dominating in the inner regions. The inferred H2O abundance profiles for L1544 require that the outer parts of the core and also any medium exterior to the core are essentially transparent to the interstellar radiation field.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is causing a global pandemic, and cases continue to rise. Most infected individuals experience mildly symptomatic coronavirus ...disease 2019 (COVID-19), but it is unknown whether this can induce persistent immune memory that could contribute to immunity. We performed a longitudinal assessment of individuals recovered from mild COVID-19 to determine whether they develop and sustain multifaceted SARS-CoV-2-specific immunological memory. Recovered individuals developed SARS-CoV-2-specific immunoglobulin (IgG) antibodies, neutralizing plasma, and memory B and memory T cells that persisted for at least 3 months. Our data further reveal that SARS-CoV-2-specific IgG memory B cells increased over time. Additionally, SARS-CoV-2-specific memory lymphocytes exhibited characteristics associated with potent antiviral function: memory T cells secreted cytokines and expanded upon antigen re-encounter, whereas memory B cells expressed receptors capable of neutralizing virus when expressed as monoclonal antibodies. Therefore, mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks of antiviral immunity.
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•Longitudinal analysis of multifaceted immune memory following mild COVID-19•Antibodies capable of neutralizing virus persist for at least 3 months in most subjects•Virus-specific memory B and T cells display hallmarks of anti-viral immunity•MBCs increase in number and express antibodies capable of neutralizing SARS-CoV-2
Longitudinal analysis of immune memory following mild COVID-19 elicits memory lymphocytes that persist and display functional hallmarks of antiviral immunity.
Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells ...facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (T
) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell-derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell-derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell-intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for T
differentiation and autoimmune GC formation.
Humoral immunity consists of pre-existing antibodies expressed by long-lived plasma cells and rapidly reactive memory B cells (MBC). Recent studies of MBC development and function after protein ...immunization have uncovered significant MBC heterogeneity. To clarify functional roles for distinct MBC subsets during malaria infection, we generated tetramers that identify Plasmodium-specific MBCs in both humans and mice. Long-lived murine Plasmodium-specific MBCs consisted of three populations: somatically hypermutated immunoglobulin M+ (IgM+) and IgG+ MBC subsets and an unmutated IgD+ MBC population. Rechallenge experiments revealed that high affinity, somatically hypermutated Plasmodium-specific IgM+ MBCs proliferated and gave rise to antibody-secreting cells that dominated the early secondary response to parasite rechallenge. IgM+ MBCs also gave rise to T cell-dependent IgM+ and IgG+B220+CD138+ plasmablasts or T cell-independent B220−CD138+ IgM+ plasma cells. Thus, even in competition with IgG+ MBCs, IgM+ MBCs are rapid, plastic, early responders to a secondary Plasmodium rechallenge and should be targeted by vaccine strategies.
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•Tetramers allow analyses of endogenous Plasmodium-specific B cells in mice and humans•Three phenotypically distinct MBC populations form after murine malaria infection•Plasmodium-specific IgM+ MBCs are somatically hypermutated and high affinity•Plastic IgM+ memory B cells dominate the early response to malaria rechallenge
Heterogeneous types of memory B cells are present in both humans and mice, yet it is unclear how different MBC subsets form or function in response to infection. Pepper and colleagues reveal that phenotypically and functionally distinct populations of polyclonal Plasmodium-specific MBCs form in response to infection and somatically hypermutated, high-affinity, plastic IgM+ memory B cells dominate the early memory response to malaria rechallenge.
The old, red stars that constitute the bulges of galaxies, and the massive black holes at their centres, are the relics of a period in cosmic history when galaxies formed stars at remarkable rates ...and active galactic nuclei (AGN) shone brightly as a result of accretion onto black holes. It is widely suspected, but unproved, that the tight correlation between the mass of the black hole and the mass of the stellar bulge results from the AGN quenching the surrounding star formation as it approaches its peak luminosity. X-rays trace emission from AGN unambiguously, whereas powerful star-forming galaxies are usually dust-obscured and are brightest at infrared and submillimetre wavelengths. Here we report submillimetre and X-ray observations that show that rapid star formation was common in the host galaxies of AGN when the Universe was 2-6 billion years old, but that the most vigorous star formation is not observed around black holes above an X-ray luminosity of 10(44) ergs per second. This suppression of star formation in the host galaxy of a powerful AGN is a key prediction of models in which the AGN drives an outflow, expelling the interstellar medium of its host and transforming the galaxy's properties in a brief period of cosmic time.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To date, most simulations of the chemistry in protoplanetary discs have used 1 + 1D or 2D axisymmetric α-disc models to determine chemical compositions within young systems. This assumption is ...inappropriate for non-axisymmetric, gravitationally unstable discs, which may be a significant stage in early protoplanetary disc evolution. Using 3D radiative hydrodynamics, we have modelled the physical and chemical evolution of a 0.17 M⊙ self-gravitating disc over a period of 2000 yr. The 0.8 M⊙ central protostar is likely to evolve into a solar-like star, and hence this Class 0 or early Class I young stellar object may be analogous to our early Solar system. Shocks driven by gravitational instabilities enhance the desorption rates, which dominate the changes in gas-phase fractional abundances for most species. We find that at the end of the simulation, a number of species distinctly trace the spiral structure of our relatively low-mass disc, particularly CN. We compare our simulation to that of a more massive disc, and conclude that mass differences between gravitationally unstable discs may not have a strong impact on the chemical composition. We find that over the duration of our simulation, successive shock heating has a permanent effect on the abundances of HNO, CN and NH3, which may have significant implications for both simulations and observations. We also find that HCO+ may be a useful tracer of disc mass. We conclude that gravitational instabilities induced in lower mass discs can significantly, and permanently, affect the chemical evolution, and that observations with high-resolution instruments such as Atacama Large Millimeter/submillimeter Array (ALMA) offer a promising means of characterizing gravitational instabilities in protosolar discs.
Bone resorption by osteoclasts requires a large number of lysosomes that release proteases in the resorption lacuna. Whether lysosomal biogenesis is a consequence of the action of transcriptional ...regulators of osteoclast differentiation or is under the control of a different and specific transcriptional pathway remains unknown. We show here, through cell-based assays and cell-specific gene deletion experiments in mice, that the osteoclast differentiation factor RANKL promotes lysosomal biogenesis once osteoclasts are differentiated through the selective activation of TFEB, a member of the MITF/TFE family of transcription factors. This occurs following PKCβ phosphorylation of TFEB on three serine residues located in its last 15 amino acids. This post-translational modification stabilizes and increases the activity of this transcription factor. Supporting these biochemical observations, mice lacking in osteoclasts--either TFEB or PKCβ--show decreased lysosomal gene expression and increased bone mass. Altogether, these results uncover a RANKL-dependent signaling pathway taking place in differentiated osteoclasts and culminating in the activation of TFEB to enhance lysosomal biogenesis-a necessary step for proper bone resorption.
The PTPN22 1858T variant was among the first single nucleotide polymorphisms to be associated with multiple autoimmune diseases. Lymphocyte tyrosine phosphatase, a coding variant within the tyrosine ...phosphatases, is known to participate in AgR signaling; the impact of this variant on the immune response and its role in the development of autoimmunity have been a focus of study. These studies used a series of approaches, including transfected cell lines, animal models, and primary human lymphocytes, and identified multiple alterations in cell signaling and function linked to the PTPN22 variant. Conflicting findings led to questions of how best to study the role of this variant in human autoimmunity. In this review, we discuss these differences and the factors that may account for them, as well as show how an integrated approach can lead to a more complete understanding of the mechanisms that promote autoimmunity in the context of the PTPN22 1858T risk variant.