Variability of strain engraftment and predictability of microbiome composition after fecal microbiota transplantation across different diseases.
Nature medicine
Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols.
10.1038/s41591-022-01964-3
Color, composition, and thermal environment of Kuiper Belt object (486958) Arrokoth.
Grundy W M,Bird M K,Britt D T,Cook J C,Cruikshank D P,Howett C J A,Krijt S,Linscott I R,Olkin C B,Parker A H,Protopapa S,Ruaud M,Umurhan O M,Young L A,Dalle Ore C M,Kavelaars J J,Keane J T,Pendleton Y J,Porter S B,Scipioni F,Spencer J R,Stern S A,Verbiscer A J,Weaver H A,Binzel R P,Buie M W,Buratti B J,Cheng A,Earle A M,Elliott H A,Gabasova L,Gladstone G R,Hill M E,Horanyi M,Jennings D E,Lunsford A W,McComas D J,McKinnon W B,McNutt R L,Moore J M,Parker J W,Quirico E,Reuter D C,Schenk P M,Schmitt B,Showalter M R,Singer K N,Weigle G E,Zangari A M
Science (New York, N.Y.)
The outer Solar System object (486958) Arrokoth (provisional designation 2014 MU) has been largely undisturbed since its formation. We studied its surface composition using data collected by the New Horizons spacecraft. Methanol ice is present along with organic material, which may have formed through irradiation of simple molecules. Water ice was not detected. This composition indicates hydrogenation of carbon monoxide-rich ice and/or energetic processing of methane condensed on water ice grains in the cold, outer edge of the early Solar System. There are only small regional variations in color and spectra across the surface, which suggests that Arrokoth formed from a homogeneous or well-mixed reservoir of solids. Microwave thermal emission from the winter night side is consistent with a mean brightness temperature of 29 ± 5 kelvin.
10.1126/science.aay3705
Composition-dependent thermodynamics of intracellular phase separation.
Riback Joshua A,Zhu Lian,Ferrolino Mylene C,Tolbert Michele,Mitrea Diana M,Sanders David W,Wei Ming-Tzo,Kriwacki Richard W,Brangwynne Clifford P
Nature
Intracellular bodies such as nucleoli, Cajal bodies and various signalling assemblies represent membraneless organelles, or condensates, that form via liquid-liquid phase separation (LLPS). Biomolecular interactions-particularly homotypic interactions mediated by self-associating intrinsically disordered protein regions-are thought to underlie the thermodynamic driving forces for LLPS, forming condensates that can facilitate the assembly and processing of biochemically active complexes, such as ribosomal subunits within the nucleolus. Simplified model systems have led to the concept that a single fixed saturation concentration is a defining feature of endogenous LLPS, and has been suggested as a mechanism for intracellular concentration buffering. However, the assumption of a fixed saturation concentration remains largely untested within living cells, in which the richly multicomponent nature of condensates could complicate this simple picture. Here we show that heterotypic multicomponent interactions dominate endogenous LLPS, and give rise to nucleoli and other condensates that do not exhibit a fixed saturation concentration. As the concentration of individual components is varied, their partition coefficients change in a manner that can be used to determine the thermodynamic free energies that underlie LLPS. We find that heterotypic interactions among protein and RNA components stabilize various archetypal intracellular condensates-including the nucleolus, Cajal bodies, stress granules and P-bodies-implying that the composition of condensates is finely tuned by the thermodynamics of the underlying biomolecular interaction network. In the context of RNA-processing condensates such as the nucleolus, this manifests in the selective exclusion of fully assembled ribonucleoprotein complexes, providing a thermodynamic basis for vectorial ribosomal RNA flux out of the nucleolus. This methodology is conceptually straightforward and readily implemented, and can be broadly used to extract thermodynamic parameters from microscopy images. These approaches pave the way for a deeper understanding of the thermodynamics of multicomponent intracellular phase behaviour and its interplay with the nonequilibrium activity that is characteristic of endogenous condensates.
10.1038/s41586-020-2256-2
Sedimentary parameters control the sulfur isotope composition of marine pyrite.
Science (New York, N.Y.)
Reconstructions of coupled carbon, oxygen, and sulfur cycles rely heavily on sedimentary pyrite sulfur isotope compositions (δS). With a model of sediment diagenesis, paired with global datasets of sedimentary parameters, we show that the wide range of δS (~100 per mil) in modern marine sediments arises from geographic patterns in the relative rates of diffusion, burial, and microbial reduction of sulfate. By contrast, the microbial sulfur isotope fractionation remains large and relatively uniform. Over Earth history, the effect of increasing seawater sulfate and oxygen concentrations on sulfate and sulfide transport and reaction may explain the corresponding increase observed in the δS offset between sulfate and pyrite. More subtle variations may be related to changes in depositional environments associated with sea level fluctuations and supercontinent cycles.
10.1126/science.adh1215
A New Phase of Networking: The Molecular Composition and Regulatory Dynamics of Mammalian Stress Granules.
Chemical reviews
Stress granules (SGs) are cytosolic biomolecular condensates that form in response to cellular stress. Weak, multivalent interactions between their protein and RNA constituents drive their rapid, dynamic assembly through phase separation coupled to percolation. Though a consensus model of SG function has yet to be determined, their perceived implication in cytoprotective processes (, antiviral responses and inhibition of apoptosis) and possible role in the pathogenesis of various neurodegenerative diseases (, amyotrophic lateral sclerosis and frontotemporal dementia) have drawn great interest. Consequently, new studies using numerous cell biological, genetic, and proteomic methods have been performed to unravel the mechanisms underlying SG formation, organization, and function and, with them, a more clearly defined SG proteome. Here, we provide a consensus SG proteome through literature curation and an update of the user-friendly database RNAgranuleDB to version 2.0 (http://rnagranuledb.lunenfeld.ca/). With this updated SG proteome, we use next-generation phase separation prediction tools to assess the predisposition of SG proteins for phase separation and aggregation. Next, we analyze the primary sequence features of intrinsically disordered regions (IDRs) within SG-resident proteins. Finally, we review the protein- and RNA-level determinants, including post-translational modifications (PTMs), that regulate SG composition and assembly/disassembly dynamics.
10.1021/acs.chemrev.2c00608
FilamentID reveals the composition and function of metabolic enzyme polymers during gametogenesis.
Cell
Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a "filament identification" (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.
10.1016/j.cell.2024.04.026
Homogenizing out-of-plane cation composition in perovskite solar cells.
Nature
Perovskite solar cells with the formula FACsPbI, where FA is formamidinium, provide an attractive option for integrating high efficiency, durable stability and compatibility with scaled-up fabrication. Despite the incorporation of Cs cations, which could potentially enable a perfect perovskite lattice, the compositional inhomogeneity caused by A-site cation segregation is likely to be detrimental to the photovoltaic performance of the solar cells. Here we visualized the out-of-plane compositional inhomogeneity along the vertical direction across perovskite films and identified the underlying reasons for the inhomogeneity and its potential impact for devices. We devised a strategy using 1-(phenylsulfonyl)pyrrole to homogenize the distribution of cation composition in perovskite films. The resultant p-i-n devices yielded a certified steady-state photon-to-electron conversion efficiency of 25.2% and durable stability.
10.1038/s41586-023-06784-0
Microbial transformation of dietary xenobiotics shapes gut microbiome composition.
Cell
Diet is a major determinant of gut microbiome composition, and variation in diet-microbiome interactions may contribute to variation in their health consequences. To mechanistically understand these relationships, here we map interactions between ∼150 small-molecule dietary xenobiotics and the gut microbiome, including the impacts of these compounds on community composition, the metabolic activities of human gut microbes on dietary xenobiotics, and interindividual variation in these traits. Microbial metabolism can toxify and detoxify these compounds, producing emergent interactions that explain community-specific remodeling by dietary xenobiotics. We identify the gene and enzyme responsible for detoxification of one such dietary xenobiotic, resveratrol, and demonstrate that this enzyme contributes to interindividual variation in community remodeling by resveratrol. Together, these results systematically map interactions between dietary xenobiotics and the gut microbiome and connect toxification and detoxification to interpersonal differences in microbiome response to diet.
10.1016/j.cell.2024.08.038
Composition and functions of bacterial membrane vesicles.
Nature reviews. Microbiology
Extracellular vesicles are produced by species across all domains of life, suggesting that vesiculation represents a fundamental principle of living matter. In Gram-negative bacteria, membrane vesicles (MVs) can originate either from blebs of the outer membrane or from endolysin-triggered explosive cell lysis, which is often induced by genotoxic stress. Although less is known about the mechanisms of vesiculation in Gram-positive and Gram-neutral bacteria, recent research has shown that both lysis and blebbing mechanisms also exist in these organisms. Evidence has accumulated over the past years that different biogenesis routes lead to distinct types of MV with varied structure and composition. In this Review, we discuss the different types of MV and their potential cargo packaging mechanisms. We summarize current knowledge regarding how MV composition determines their various functions including support of bacterial growth via the disposal of waste material, nutrient scavenging, export of bioactive molecules, DNA transfer, neutralization of phages, antibiotics and bactericidal functions, delivery of virulence factors and toxins to host cells and inflammatory and immunomodulatory effects. We also discuss the advantages of MV-mediated secretion compared with classic bacterial secretion systems and we introduce the concept of quantal secretion.
10.1038/s41579-023-00875-5