The widespread deployment of carbon capture and sequestration as a climate change mitigation strategy could be facilitated by the development of more energy-efficient adsorbents. Diamine-appended ...metal–organic frameworks of the type diamine–M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4– = 4,4′-dioxidobiphenyl-3,3′-dicarboxylate) have shown promise for carbon-capture applications, although questions remain regarding the molecular mechanisms of CO2 uptake in these materials. Here we leverage the crystallinity and tunability of this class of frameworks to perform a comprehensive study of CO2 chemisorption. Using multinuclear nuclear magnetic resonance (NMR) spectroscopy experiments and van-der-Waals-corrected density functional theory (DFT) calculations for 13 diamine–M2(dobpdc) variants, we demonstrate that the canonical CO2 chemisorption products, ammonium carbamate chains and carbamic acid pairs, can be readily distinguished and that ammonium carbamate chain formation dominates for diamine–Mg2(dobpdc) materials. In addition, we elucidate a new chemisorption mechanism in the material dmpn–Mg2(dobpdc) (dmpn = 2,2-dimethyl-1,3-diaminopropane), which involves the formation of a 1:1 mixture of ammonium carbamate and carbamic acid and accounts for the unusual adsorption properties of this material. Finally, we show that the presence of water plays an important role in directing the mechanisms for CO2 uptake in diamine–M2(dobpdc) materials. Overall, our combined NMR and DFT approach enables a thorough depiction and understanding of CO2 adsorption within diamine–M2(dobpdc) compounds, which may aid similar studies in other amine-functionalized adsorbents in the future.
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IJS, KILJ, NUK, PNG, UL, UM
Chronic inflammation is often associated with the development of tissue fibrosis, but how mesenchymal cell responses dictate pathological fibrosis versus resolution and healing remains unclear. ...Defining stromal heterogeneity and identifying molecular circuits driving extracellular matrix deposition and remodeling stands to illuminate the relationship between inflammation, fibrosis, and healing. We performed single-cell RNA-sequencing of colon-derived stromal cells and identified distinct classes of fibroblasts with gene signatures that are differentially regulated by chronic inflammation, including IL-11-producing inflammatory fibroblasts. We further identify a transcriptional program associated with trans-differentiation of mucosa-associated fibroblasts and define a functional gene signature associated with matrix deposition and remodeling in the inflamed colon. Our analysis supports a critical role for the metalloprotease Adamdec1 at the interface between tissue remodeling and healing during colitis, demonstrating its requirement for colon epithelial integrity. These findings provide mechanistic insight into how inflammation perturbs stromal cell behaviors to drive fibroblastic responses controlling mucosal matrix remodeling and healing.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
According to the hygiene hypothesis, the increasing incidence of autoimmune diseases in western countries may be explained by changes in early microbial exposure, leading to altered immune ...maturation. We followed gut microbiome development from birth until age three in 222 infants in Northern Europe, where early-onset autoimmune diseases are common in Finland and Estonia but are less prevalent in Russia. We found that Bacteroides species are lowly abundant in Russians but dominate in Finnish and Estonian infants. Therefore, their lipopolysaccharide (LPS) exposures arose primarily from Bacteroides rather than from Escherichia coli, which is a potent innate immune activator. We show that Bacteroides LPS is structurally distinct from E. coli LPS and inhibits innate immune signaling and endotoxin tolerance; furthermore, unlike LPS from E. coli, B. dorei LPS does not decrease incidence of autoimmune diabetes in non-obese diabetic mice. Early colonization by immunologically silencing microbiota may thus preclude aspects of immune education.
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•Finnish and Estonian infants have a distinct early gut microbiome compared to Russians•B. dorei and other Bacteroides species are highly abundant in Finland and Estonia•B. dorei LPS inhibits the immunostimulatory activity of E. coli LPS•LPS from B. dorei does not protect NOD mice from type 1 diabetes
Bacteroides species in the microbiota of children from countries with high susceptibility to autoimmunity produce a type of lipopolysaccharide (LPS) with immunoinhibitory properties. These properties may preclude early immune education and contribute to the development of type 1 diabetes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions ...such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits.
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•Computational analysis identifies Peptostreptococcus russellii as a mucin utilizer•Peptostreptococcus species produce the tryptophan metabolite indoleacrylic acid (IA)•IA promotes intestinal epithelial barrier function and mitigates inflammatory responses•Microbes of IBD patients have reduced ability to cleave mucins and metabolize tryptophan
Wlodarska et al. provide insight into intestinal mucin as an exemplar of a critical host-derived colonization factor that attracts bacteria that may promote intestinal health. One such mucin utilizer, Peptostreptococcus russellii, produces the tryptophan metabolite indoleacrylic acid, which has beneficial effects on intestinal epithelial barrier function and mitigates inflammatory responses.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been ...associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Sphingolipids are structural membrane components and important eukaryotic signaling molecules. Sphingolipids regulate inflammation and immunity and were recently identified as the most differentially ...abundant metabolite in stool from inflammatory bowel disease (IBD) patients. Commensal bacteria from the Bacteroidetes phylum also produce sphingolipids, but the impact of these metabolites on host pathways is largely uncharacterized. To determine whether bacterial sphingolipids modulate intestinal health, we colonized germ-free mice with a sphingolipid-deficient Bacteroides thetaiotaomicron strain. A lack of Bacteroides-derived sphingolipids resulted in intestinal inflammation and altered host ceramide pools in mice. Using lipidomic analysis, we described a sphingolipid biosynthesis pathway and revealed a variety of Bacteroides-derived sphingolipids including ceramide phosphoinositol and deoxy-sphingolipids. Annotating Bacteroides sphingolipids in an IBD metabolomic dataset revealed lower abundances in IBD and negative correlations with inflammation and host sphingolipid production. These data highlight the role of bacterial sphingolipids in maintaining homeostasis and symbiosis in the gut.
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•Colonization with a sphingolipid-deficient Bacteroides strain is pro-inflammatory•Metabolomics describe Bacteroides sphingolipids and their biosynthetic pathway•IBD patients have decreased Bacteroides sphingolipids but increased host sphingolipids
In this issue, Brown et al. discover a number of bacterial sphingolipid metabolites and demonstrate that sphingolipid production by Bacteroides species in the gut microbiome promotes symbiosis with the host. Bacterial sphingolipid deficiency correlates with inflammatory bowel disease and increased host-produced sphingolipid abundance in the human intestine.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino ...acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Chiral metal–organic frameworks have attracted interest for enantioselective separations and catalysis because of their high crystallinity and pores with tunable shapes, sizes, and chemical ...environments. Chiral frameworks of the type M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4– = 4,4′-dioxidobiphenyl-3,3′-dicarboxylate) seem particularly promising for potential applications because of their excellent stability, high internal surface areas, and strongly polarizing open metal coordination sites within the channels, but to date these materials have been isolated only in racemic form. Here, we demonstrate that when appended with the chiral diamine trans-1,2-diaminocyclohexane (dach), Mg2(dobpdc) adsorbs carbon dioxide cooperatively to form ammonium carbamate chains, and the thermodynamics of CO2 capture are strongly influenced by enantioselective interactions within the chiral pores of the framework. We further show that it is possible to access both enantiomers of Mg2(dobpdc) with high enantiopurity (≥90%) via framework synthesis in the presence of varying quantities of d-panthenol, an inexpensive chiral induction agent. Investigation of dach–M2(dobpdc) samples following CO2 adsorptionusing single-crystal and powder X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, and density functional theory calculationsrevealed that the ammonium carbamate chains interact extensively with each other and with the chiral M2(dobpdc) pore walls. Subtle differences in the non-covalent interactions accessible in each diastereomeric phase dramatically impact the thermodynamics of CO2 adsorption.
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IJS, KILJ, NUK, PNG, UL, UM
Scholars and practitioners alike in recent years have suggested that real and lasting progress in the fight against gun violence requires changing the social norms and attitudes that perpetuate ...violence and the use of guns. The Cure Violence model is a public health approach to gun violence reduction that seeks to change individual and community attitudes and norms about gun violence. It considers gun violence to be analogous to a communicable disease that passes from person to person when left untreated. Cure Violence operates independently of, while hopefully not undermining, law enforcement. In this article, we describe the theoretical basis for the program, review existing program evaluations, identify several challenges facing evaluators, and offer directions for future research.
A series of structurally diverse alcoholamine‐ and alkoxyalkylamine‐functionalized variants of the metal–organic framework Mg2(dobpdc) are shown to adsorb CO2 selectively via cooperative ...chain‐forming mechanisms. Solid‐state NMR spectra and optimized structures obtained from van der Waals‐corrected density functional theory calculations indicate that the adsorption profiles can be attributed to the formation of carbamic acid or ammonium carbamate chains that are stabilized by hydrogen bonding interactions within the framework pores. These findings significantly expand the scope of chemical functionalities that can be utilized to design cooperative CO2 adsorbents, providing further means of optimizing these powerful materials for energy‐efficient CO2 separations.
Cooperative CO2 chemisorption is achieved in a metal–organic framework functionalized with structurally diverse alcoholamines and alkoxyalkylamines. Solid‐state NMR spectroscopy and DFT calculations indicate that CO2 adsorption occurs via the formation and propagation of hydrogen bond‐stabilized carbamic acid or ammonium carbamate structures.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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