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Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion.
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Desenvolvimento Infantil , Desnutrição/dietoterapia , Leite Humano/química , Leite/química , Oligossacarídeos/metabolismo , Animais , Bacteroides fragilis/genética , Bifidobacterium/classificação , Bifidobacterium/genética , Química Encefálica , Modelos Animais de Doenças , Escherichia coli/genética , Fezes/microbiologia , Vida Livre de Germes , Humanos , Lactente , Malaui , Masculino , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , MicrobiotaRESUMO
Microbiota assembly is perturbed in children with undernutrition, resulting in persistent microbiota immaturity that is not rescued by current nutritional interventions. Evidence is accumulating that this immaturity is causally related to the pathogenesis of undernutrition and its lingering sequelae. Preclinical models in which human gut communities are replicated in gnotobiotic mice have provided an opportunity to identify and predict the effects of different dietary ingredients on microbiota structure, expressed functions, and host biology. This capacity sets the stage for proof-of-concept tests designed to deliberately shape the developmental trajectory and configurations of microbiota in children representing different geographies, cultural traditions, and states of health. Developing these capabilities for microbial stewardship is timely given the global health burden of childhood undernutrition, the effects of changing eating practices brought about by globalization, and the realization that affordable nutritious foods need to be developed to enhance our capacity to cultivate healthier microbiota in populations at risk for poor nutrition.
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Desenvolvimento Infantil , Trato Gastrointestinal/microbiologia , Microbiota , Animais , Criança , Fenômenos Fisiológicos da Nutrição Infantil , Feminino , Humanos , Troca Materno-Fetal , GravidezRESUMO
Micronutrient deficiencies account for an estimated one million premature deaths annually, and for some nations can reduce gross domestic product1,2 by up to 11%, highlighting the need for food policies that focus on improving nutrition rather than simply increasing the volume of food produced3. People gain nutrients from a varied diet, although fish-which are a rich source of bioavailable micronutrients that are essential to human health4-are often overlooked. A lack of understanding of the nutrient composition of most fish5 and how nutrient yields vary among fisheries has hindered the policy shifts that are needed to effectively harness the potential of fisheries for food and nutrition security6. Here, using the concentration of 7 nutrients in more than 350 species of marine fish, we estimate how environmental and ecological traits predict nutrient content of marine finfish species. We use this predictive model to quantify the global spatial patterns of the concentrations of nutrients in marine fisheries and compare nutrient yields to the prevalence of micronutrient deficiencies in human populations. We find that species from tropical thermal regimes contain higher concentrations of calcium, iron and zinc; smaller species contain higher concentrations of calcium, iron and omega-3 fatty acids; and species from cold thermal regimes or those with a pelagic feeding pathway contain higher concentrations of omega-3 fatty acids. There is no relationship between nutrient concentrations and total fishery yield, highlighting that the nutrient quality of a fishery is determined by the species composition. For a number of countries in which nutrient intakes are inadequate, nutrients available in marine finfish catches exceed the dietary requirements for populations that live within 100 km of the coast, and a fraction of current landings could be particularly impactful for children under 5 years of age. Our analyses suggest that fish-based food strategies have the potential to substantially contribute to global food and nutrition security.
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Pesqueiros , Peixes/metabolismo , Abastecimento de Alimentos , Internacionalidade , Micronutrientes/deficiência , Micronutrientes/metabolismo , Estado Nutricional , Animais , Teorema de Bayes , Cálcio/análise , Pré-Escolar , Proteínas Alimentares/análise , Ácidos Graxos Ômega-3/análise , Produtos Pesqueiros/análise , Produtos Pesqueiros/economia , Pesqueiros/economia , Peixes/classificação , Humanos , Lactente , Ferro/análise , Micronutrientes/análise , Selênio/análise , Vitamina A/análise , Zinco/análiseRESUMO
The isolation of formally two-coordinate lanthanide (Ln) complexes is synthetically challenging, due to predominantly ionic Ln bonding regimes favoring high coordination numbers. In 2015, it was predicted that a near-linear dysprosium bis(amide) cation [Dy{N(SiiPr3)2}2]+ could provide a single-molecule magnet (SMM) with an energy barrier to magnetic reversal (Ueff) of up to 2600 K, a 3-fold increase of the record Ueff for a Dy SMM at the time; this work showed a potential route to SMMs that can provide high-density data storage at higher temperatures. However, synthetic routes to a Dy complex containing only two monodentate ligands have not previously been realized. Here, we report the synthesis of the target bent dysprosium bis(amide) complex, [Dy{N(SiiPr3)2}2][Al{OC(CF3)3}4] (1-Dy), together with the diamagnetic yttrium analogue. We find Ueff = 950 ± 30 K for 1-Dy, which is much lower than the predicted values for idealized linear two-coordinate Dy(III) cations. Ab initio calculations of the static electronic structure disagree with the experimentally determined height of the Ueff barrier, thus magnetic relaxation is faster than expected based on magnetic anisotropy alone. We propose that this is due to enhanced spin-phonon coupling arising from the flexibility of the Dy coordination sphere, in accord with ligand vibrations being of equal importance to magnetic anisotropy in the design of high-temperature SMMs.
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We present pulsed electron paramagnetic resonance (EPR) studies on three La(II) complexes, [K(2.2.2-cryptand)][La(Cp')3] (1), [K(2.2.2-cryptand)][La(Cpâ³)3] (2), and [K(2.2.2-cryptand)][La(Cptt)3] (3), which feature cyclopentadienyl derivatives as ligands [Cp' = C5H4SiMe3; Cpâ³ = C5H3(SiMe3)2; Cptt = C5H3(CMe3)2] and display a C3 symmetry. Long spin-lattice relaxation (T1) and phase memory (Tm) times are observed for all three compounds, but with significant variation in T1 among 1-3, with 3 being the slowest relaxing due to higher s-character of the SOMO. The dephasing times can be extended by more than an order of magnitude via dynamical decoupling experiments using a Carr-Purcell-Meiboom-Gill (CPMG) sequence, reaching 161 µs (5 K) for 3. Coherent spin manipulation is performed by the observation of Rabi quantum oscillations up to 80 K in this nuclear spin-rich environment (1H, 13C, and 29Si). The high nuclear spin of 139La (I = 7/2), and the ability to coherently manipulate all eight hyperfine transitions, makes these molecules promising candidates for application as qudits (multilevel quantum systems featuring d quantum states; d >2) for performing quantum operations within a single molecule. Application of HYSCORE techniques allows us to quantify the electron spin density at ligand nuclei and interrogate the role of functional groups to the electron spin relaxation properties.
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Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.
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Microbioma Gastrointestinal , Espectrometria de Massa com Cromatografia Líquida , Humanos , Camundongos , Animais , Cromatografia Líquida , Microbioma Gastrointestinal/fisiologia , Espectrometria de Massas em Tandem , Ácidos Graxos Voláteis/metabolismoRESUMO
Members of the mammalian gut microbiota metabolize diverse complex carbohydrates that are not digested by the host, which are collectively labeled "dietary fiber." While the enzymes and transporters that each strain uses to establish a nutrient niche in the gut are often exquisitely specific, the relationship between carbohydrate structure and microbial ecology is imperfectly understood. The present study takes advantage of recent advances in complex carbohydrate structure determination to test the effects of fiber monosaccharide composition on microbial fermentation. Fifty-five fibers with varied monosaccharide composition were fermented by a pooled feline fecal inoculum in a modified MiniBioReactor array system over a period of 72 hours. The content of the monosaccharides glucose and xylose was significantly associated with the reduction of pH during fermentation, which was also predictable from the concentrations of the short-chain fatty acids lactic acid, propionic acid, and the signaling molecule indole-3-acetic acid. Microbiome diversity and composition were also predictable from monosaccharide content and SCFA concentration. In particular, the concentrations of lactic acid and propionic acid correlated with final alpha diversity and were significantly associated with the relative abundance of several of the genera, including Lactobacillus and Dubosiella. Our results suggest that monosaccharide composition offers a generalizable method to compare any dietary fiber of interest and uncover links between diet, gut microbiota, and metabolite production. IMPORTANCE: The survival of a microbial species in the gut depends on the availability of the nutrients necessary for that species to survive. Carbohydrates in the form of non-host digestible fiber are of particular importance, and the set of genes possessed by each species for carbohydrate consumption can vary considerably. Here, differences in the monosaccharides that are the building blocks of fiber are considered for their impact on both the survival of different species of microbes and on the levels of microbial fermentation products produced. This work demonstrates that foods with similar monosaccharide content will have consistent effects on the survival of microbial species and on the production of microbial fermentation products.
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Bactérias , Fibras na Dieta , Fermentação , Microbioma Gastrointestinal , Monossacarídeos , Fibras na Dieta/metabolismo , Monossacarídeos/metabolismo , Monossacarídeos/análise , Animais , Bactérias/classificação , Bactérias/metabolismo , Bactérias/genética , Fezes/microbiologia , Fezes/química , Ácidos Graxos Voláteis/metabolismoRESUMO
Dysprosium complexes with strong axial crystal fields are promising candidates for single-molecule magnets (SMMs), which could be used for high-density data storage. Isolated dysprosocenium cations, [Dy(CpR)2]+ (CpR = substituted cyclopentadienyl), have recently shown magnetic hysteresis (a memory effect) above the temperature of liquid nitrogen. Synthetic efforts have focused on reducing strong transverse ligand fields in these systems as they are known to enhance magnetic relaxation by spin-phonon mechanisms. Here we show that equatorial coordination of the halobenzenes PhX (X = F, Cl, Br) and o-C6H4F2 to the cation of a recently reported dysprosocenium complex [Dy(Cpttt)(Cp*)][Al{OC(CF3)3}4] (Cpttt = C5H2tBu3-1,2,4; Cp* = C5Me5) reduces magnetic hysteresis temperatures compared to that of the parent cation. We find that this is due to increased effectiveness of both one- (Orbach) and two-phonon (Raman) relaxation mechanisms, which correlate with the electronegativity and number of interactions with the halide despite κ1-coordination of a single halobenzene having a minimal effect on the metrical parameters of [Dy(Cpttt)(Cp*)(PhX-κ1-X)]+ cations vs the isolated [Dy(Cpttt)(Cp*)]+ cation. We observe unusual divergent behavior of relaxation rates at low temperatures in [Dy(Cpttt)(Cp*)(PhX)][Al{OC(CF3)3}4], which we attribute to a phonon bottleneck effect. We find that, despite the transverse fields introduced by the monohalobenzenes in these cations, the interactions are sufficiently weak that the effective barriers to magnetization reversal remain above 1000 cm-1, being only ca. 100 cm-1 lower than for the parent complex, [Dy(Cpttt)(Cp*)][Al{OC(CF3)3}4].
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The decamethyldysprosocenium cation, [Dy(Cp*)2]+ (Cp* = {C5Me5}), was a target single-molecule magnet (SMM) prior to the isolation of larger dysprosocenium cations, which have recently shown magnetic memory effects up to 80 K. However, the relatively short Dy···Cp*centroid distances of [Dy(Cp*)2]+, together with the reduced resonance of its vibrational modes with electronic states compared to larger dysprosocenium cations, could lead to more favorable SMM behavior. Here, we report the synthesis and magnetic properties of a series of solvated adducts containing bis-halobenzene decamethyldysprosocenium cations, namely [Dy(Cp*)2(PhX-κ-X)2][Al{OC(CF3)3}4] (X = F or Cl) and [Dy(Cp*)2(C6H4F2-κ2-F,F)(C6H4F2-κ-F)][Al{OC(CF3)3}4]. These complexes were prepared by the sequential reaction of [Dy(Cp*)2(µ-BH4)]∞ with allylmagnesium chloride and [NEt3H][Al{OC(CF3)3}4], followed by recrystallization from parent halobenzenes. The complexes were characterized by powder and single crystal X-ray diffraction, NMR and ATR-IR spectroscopy, elemental analysis, and SQUID magnetometry; experimental data were rationalized by a combination of density functional theory and ab initio calculations. We find that bis-halobenzene adducts of the [Dy(Cp*)2]+ cation exhibit highly bent Cp*···Dy···Cp* angles; these cations are also susceptible to decomposition by C-X (X = F, Cl, Br) activation and displacement of halobenzenes by O-donor ligands. The effective energy barrier to reversal of magnetization measured for [Dy(Cp*)2(PhF-κ-F)2][Al{OC(CF3)3}4] (930(6) cm-1) sets a new record for SMMs containing {Dy(Cp*)2} fragments, though all SMM parameters are lower than would be predicted for an isolated [Dy(Cp*)2]+ cation, as expected due to transverse ligand fields introduced by halobenzenes and the large deviation of the Cp*···Dy···Cp* angle from linearity promoting magnetic relaxation.
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Over the past decade, the phenomenon of "fake" peer reviews has caused growing consternation among scholarly publishers. Yet despite the significant behind-the-scenes impact that anxieties about fakery have had on peer review processes within scholarly journals, the phenomenon itself has been subject to little scholarly analysis. Rather than treating fake reviews as a straightforward descriptive category, in this article, we explore how the discourse on fake reviews emerged and why, and what it tells us about its seeming antithesis, "genuine" peer review. Our primary source of data are two influential adjudicators of scholarly publishing integrity that have been critical to the emergence of the concept of the fake review: Retraction Watch and the Committee on Publication Ethics. Via an analysis of their respective blog posts, Forum cases, presentations, and best practice guidance, we build a genealogy of the fake review discourse and highlight the variety of players involved in staking out the fake. We conclude that constant work is required to maintain clear lines of separation between genuine and fake reviews and highlight how the concept has served to reassert the boundaries between science and society in a context where they have increasingly been questioned.
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The thermostable four-coordinate divalent lanthanide (Ln) bis-amidinate complexes [Ln(Piso)2] (Ln = Tb, Dy; Piso = {(NDipp)2CtBu}, Dipp = C6H3iPr2-2,6) were prepared by the reduction of parent five-coordinate Ln(III) precursors [Ln(Piso)2I] (Ln = Tb, Dy) with KC8; halide abstraction of [Ln(Piso)2I] with [H(SiEt3)2][B(C6F5)] gave the respective Ln(III) complexes [Ln(Piso)2][B(C6F5)]. All complexes were characterized by X-ray diffraction, ICP-MS, elemental analysis, SQUID magnetometry, UV-vis-NIR, ATR-IR, NMR, and EPR spectroscopy and ab initio CASSCF-SO calculations. These data consistently show that [Ln(Piso)2] formally exhibit Ln(II) centers with 4fn5dz21 (Ln = Tb, n = 8; Dy, n = 9) valence electron configurations. We show that simple assignments of the f-d coupling to either L-S or J-s schemes are an oversimplification, especially in the presence of significant crystal field splitting. The coordination geometry of [Ln(Piso)2] is intermediate between square planar and tetrahedral. Projecting from the quaternary carbon atoms of the CN2 ligand backbones shows near-linear C···Ln···C arrangements. This results in strong axial ligand fields to give effective energy barriers to magnetic reversal of 1920(91) K for the Tb(II) analogue and 1964(48) K for Dy(II), the highest values observed for mononuclear Ln(II) single-molecule magnets, eclipsing 1738 K for [Tb(C5iPr5)2]. We tentatively attribute the fast zero-field magnetic relaxation for these complexes at low temperatures to transverse fields, resulting in considerable mixing of mJ states.
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Isolated dysprosocenium cations, [Dy(CpR)2]+ (CpR = substituted cyclopentadienyl), have recently been shown to exhibit superior single-molecule magnet (SMM) properties over closely related complexes with equatorially bound ligands. However, gauging the crossover point at which the CpR substituents are large enough to prevent equatorial ligand binding, but small enough to approach the metal closely and generate strong crystal field splitting has required laborious synthetic optimization. We therefore created the computer program AtomAccess to predict the accessibility of a metal binding site and its ability to accommodate additional ligands. Here, we apply AtomAccess to identify the crossover point for equatorial coordination in [Dy(CpR)2]+ cations in silico and hence predict a cation that is at the cusp of stability without equatorial interactions, viz., [Dy(Cpttt)(Cp*)]+ (Cpttt = C5H2tBu3-1,2,4, Cp* = C5Me5). Upon synthesizing this cation, we found that it crystallizes as either a contact ion-pair, [Dy(Cpttt)(Cp*){Al[OC(CF3)3]4-κ-F}], or separated ion-pair polymorph, [Dy(Cpttt)(Cp*)][Al{OC(CF3)3}4]·C6H6. Upon characterizing these complexes, together with their precursors, yttrium and yttrium-doped analogues, we find that the contact ion-pair shows inferior SMM properties to the separated ion-pair, as expected, due to faster Raman and quantum tunneling of magnetization relaxation processes, while the Orbach region is relatively unaffected. The experimental verification of the predicted crossover point for equatorial coordination in this work tests the limitations of the use of AtomAccess as a predictive tool and also indicates that the application of this type of program shows considerable potential to boost efficiency in exploratory synthetic chemistry.
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Armadillos are bitten by several species of flea. Females of the genus Tunga penetrate the epidermis and when in place are fertilised by males, after which the abdomen swells enormously to form a 'neosome'. Within the penetrans group, T. perforans, makes lesions that perforate the osteoderms within the integument to form ~3 mm diameter cavities occupied by a discoid neosome. We examined these lesions in carapace material from animals which had died in the wild to see whether we could recruit evidence as to how they may be generated, either by the insect or by the host. We studied one species without such lesions, the nine-banded armadillo Dasypus novemcinctus, and two species with, the greater hairy armadillo Chaetophractus villosus and the southern three-banded armadillo Tolypeutes matacus, both showing the characteristic 'flea bite' holes in the external surfaces of the osteoderms. Samples were studied by three-dimensional backscattered electron mode scanning electron microscopy and X-ray microtomography. Both methods showed resorption pit complexes in the external surfaces of the osteoderms characteristic of those made by osteoclasts in active bone resorption. Lesions involved both the syndesmoses (sutures) between adjacent bones and the central regions of the osteoderms. Many lesions showed extensive repair by infilling with new bone. We conclude that the T. perforans neosome creates a local host response which causes bone resorption, creating the space in which it can grow.
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Tatus , Sifonápteros , Animais , Feminino , Masculino , Tatus/fisiologia , Osso e Ossos , Pele , ArticulaçõesRESUMO
The salt metathesis reactions of the yttrium methanediide iodide complex [Y(BIPM)(I)(THF)2] (BIPM = {C(PPh2NSiMe3)2}) with the group 1 silanide ligand-transfer reagents MSiR3 (M = Na, R3 = tBu2Me or tBu3; M = K, R3 = (SiMe3)3) gave the yttrium methanediide silanide complexes [Y(BIPM)(SitBu2Me)(THF)] (1), [Y(BIPM)(SitBu3)(THF)] (2), and [Y(BIPM){Si(SiMe3)3}(THF)] (3). Complexes 1-3 provide rare examples of structurally authenticated rare earth metal-silicon bonds and were characterized by single-crystal X-ray diffraction, multinuclear NMR and ATR-IR spectroscopies, and elemental analysis. Density functional theory calculations were performed on 1-3 to probe their electronic structures further, revealing predominantly ionic Y-Si bonding. The computed Y-Si bonds show lower covalency than YâC bonds, which are in turn best represented by Y+-C- dipolar forms due to the strong σ-donor properties of the silanide ligands investigated; these observations are in accord with experimentally obtained 13C{1H} and 29Si{1H} NMR data for 1-3 and related Y(III) BIPM alkyl complexes in the literature. Preliminary reactivity studies were performed, with complex 1 treated separately with benzophenone, azobenzene, and N,N'-dicyclohexyl-carbodiimide. 29Si{1H} and 31P{1H} NMR spectra of these reaction mixtures indicated that 1,2-migratory insertion of the unsaturated substrate into the Y-Si bond is favored, while for the latter substrate, a [2 + 2]-cycloaddition reaction also occurs at the YâC bond to afford [Y{C(PPh2NSiMe3)2[C(NCy)2]-κ4C,N,N',N'}{C(NCy)2(SitBu2Me)-κ2N,N'}] (4); these reactivity profiles complement and contrast with those of Y(III) BIPM alkyl complexes.
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The pursuit of a trivalent plutonium halide phosphine oxide compound, e.g., "PuBr3(OPR)3," instead led to the isolation of the tetravalent trans-PuIVBr4(OPCy3)2, PuBr/Cy, compound by spontaneous oxidation of PuIII. The donating nature of phosphine oxides has allowed the isolation and characterization of PuBr/Cy by crystallographic, multinuclear NMR, solid state, and solution phase UV-vis-NIR spectroscopic techniques. The presence of a putative plutonyl(VI) complex formulated as "trans-PuVIO2Br2(OPCy3)2" was also observed spectroscopically and tentatively by single-crystal X-ray diffraction as a cocrystal of PuBr/Cy. A series of trans-ThX4(OPCy3)2 (X = Cl, ThCl/Cy; Br, ThBr/Cy; I, ThI/Cy) complexes were synthesized for comparison to PuBr/Cy. The triphenylphosphine oxide, OPPh3, complexes, trans-AnI4(OPPh3)2 (An = Th, ThI/Ph; U, UI/Ph), were also synthesized for comparison, completing the series trans-UX4(OPPh3)2 (X = Cl, Br, I), UX/Ph. To enable the synthesis of ThI/Cy and ThI/Ph, a new nonaqueous thorium iodide starting material, ThI4(Et2O)2, was synthesized. The syntheses of organic solvent soluble ThI4L2 (L = Et2O, OPCy3, and OPPh3) are the first examples of crystallographically characterized neutral thorium tetraiodide materials beyond binary ThI4. To show the viability of ThI4(Et2O)2 as a starting material for organothorium chemistry, (C5Me4H)3ThI was synthesized and crystallographically characterized.
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The use of magnetisation decay measurements to characterise very slow relaxation of the magnetisation in single-molecule magnets is becoming increasingly prevalent as relaxation times move to longer timescales outside of the AC susceptibility range. However, experimental limitations and a poor understanding of the distribution underlying the stretched exponential function, commonly used to model the data, may be leading to misinterpretation of the results. Herein we develop guidelines on the experimental design, data fitting, and analysis required to accurately interpret magnetisation decay measurements. Various measures of the magnetic relaxation rate extracted from magnetisation decay measurements of [Dy(Dtp)2][Al{OC(CF3)3}4] previously characterised by Evans et al., fitted using combinations of fixing or freely fitting different parameters, are compared to those obtained using the innovative square-wave "waveform" technique of Hilgar et al. The waveform technique is comparable to AC susceptometry for measurement of relaxation rates on long timescales. The most reliable measure of the relaxation time for magnetisation decays is found to be the average logarithmic relaxation time, eãln[τ]ã, obtained via a fit of the decay trace using a stretched exponential function, where the initial and equilibrium magnetisation are fixed to first measured point and target values respectively. This new definition causes the largest differences to traditional approaches in the presence of large distributions or relaxation rates, with differences up to 50% with ß = 0.45, and hence could have a significant impact on the chemical interpretation of magnetic relaxation rates. A necessary step in progressing towards chemical control of magnetic relaxation is the accurate determination of relaxation times, and such large variations in experimental measures stress the need for consistency in fitting and interpretation of magnetisation decays.
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Lanthanides have been investigated extensively for potential applications in quantum information processing and high-density data storage at the molecular and atomic scale. Experimental achievements include reading and manipulating single nuclear spins, exploiting atomic clock transitions for robust qubits and, most recently, magnetic data storage in single atoms. Single-molecule magnets exhibit magnetic hysteresis of molecular origin-a magnetic memory effect and a prerequisite of data storage-and so far lanthanide examples have exhibited this phenomenon at the highest temperatures. However, in the nearly 25 years since the discovery of single-molecule magnets, hysteresis temperatures have increased from 4 kelvin to only about 14 kelvin using a consistent magnetic field sweep rate of about 20 oersted per second, although higher temperatures have been achieved by using very fast sweep rates (for example, 30 kelvin with 200 oersted per second). Here we report a hexa-tert-butyldysprosocenium complex-[Dy(Cpttt)2][B(C6F5)4], with Cpttt = {C5H2tBu3-1,2,4} and tBu = C(CH3)3-which exhibits magnetic hysteresis at temperatures of up to 60 kelvin at a sweep rate of 22 oersted per second. We observe a clear change in the relaxation dynamics at this temperature, which persists in magnetically diluted samples, suggesting that the origin of the hysteresis is the localized metal-ligand vibrational modes that are unique to dysprosocenium. Ab initio calculations of spin dynamics demonstrate that magnetic relaxation at high temperatures is due to local molecular vibrations. These results indicate that, with judicious molecular design, magnetic data storage in single molecules at temperatures above liquid nitrogen should be possible.
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Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. Methods: In the PASTURE farm birth cohort, innate T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with LPS in n = 445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main Results: Not all cytokines were detectable in all children after LPS stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation: odds ratio (OR), 1.89; 95% confidence interval [CI], 1.13-3.16; P = 0.015. In contrast, in children with high cytokine activation after LPS stimulation, no association of the 17q21 risk allele with wheeze (OR, 0.63; 95% CI, 0.29-1.40; P = 0.258, P = 0.034 for interaction) or school-age asthma was observed. In these children, consumption of unprocessed cow's milk was associated with higher cytokine activation (OR, 3.37; 95% CI, 1.56-7.30; P = 0.002), which was in part mediated by the gut microbiome. Conclusions: These findings suggest that within the 17q21 genotype, asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
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Asma , Cromossomos Humanos Par 17 , Lipopolissacarídeos , Alelos , Animais , Asma/genética , Bovinos , Citocinas/genética , Feminino , Humanos , Imunidade Inata , Leucócitos Mononucleares , Camundongos , Sons Respiratórios/genéticaRESUMO
The pandemic necessitated a change to the historical diagnostics model [...].
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Técnicas Biossensoriais , Atenção à Saúde , PandemiasRESUMO
Based on the observations made in rheumatology clinics, autoimmune disease (AD) patients on immunosuppressive (IS) medications have variable vaccine site inflammation responses, whose study may help predict the long-term efficacy of the vaccine in this at-risk population. However, the quantitative assessment of the inflammation of the vaccine site is technically challenging. In this study analyzing AD patients on IS medications and normal control subjects, we imaged the inflammation of the vaccine site 24 h after mRNA COVID-19 vaccinations were administered using both the emerging photoacoustic imaging (PAI) method and the established Doppler ultrasound (US) method. A total of 15 subjects were involved, including 6 AD patients on IS and 9 normal control subjects, and the results from the two groups were compared. Compared to the results obtained from the control subjects, the AD patients on IS medications showed statistically significant reductions in vaccine site inflammation, indicating that immunosuppressed AD patients also experience local inflammation after mRNA vaccination but not in as clinically apparent of a manner when compared to non-immunosuppressed non-AD individuals. Both PAI and Doppler US were able to detect mRNA COVID-19 vaccine-induced local inflammation. PAI, based on the optical absorption contrast, shows better sensitivity in assessing and quantifying the spatially distributed inflammation in soft tissues at the vaccine site.