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Reduced inflammatory signaling (IL-1RI-/-) alters metabolic responses to dietary challenges (1). Inflammasome deficiency (e.g. IL-18-/-, Asc-/-) can modify gut microbiota concomitant with hepatosteatosis; an effect that was transferable to wild-type (WT) mice by co-housing (2). Taken together, this evidence suggests that links between diet, microbiota and IL-1RI-signaling can influence metabolic health. Our aim was to determine whether IL-1RI-mediated signaling interacted with the gut microbiome to impact metabolic tissue functionality in a diet-specific fashion. Male WT (C57BL/J6) and IL-1RI-/- mice were fed either high-fat diet (HFD; 45% kcal) or low-fat diet (LFD; 10% kcal) for 24 weeks and were housed i) separately by genotype or ii) with genotypes co-housed together (i.e. isolated vs shared microbial environment; n = 8–10 mice per group). Glucose tolerance and insulin secretion response (1.5 g/kg i.p.), gut microbiota composition and caecal short-chain fatty acids (SCFA) were assessed. Liver and adipose tissue were harvested and examined for triacylglycerol (TAG) formation, cholesterol and metabolic markers (Fasn, Cpt1α, Pparg, Scd1, Dgat1/2), using histology, gas-chromatography and RT-PCR, respectively. Statistical analysis included 1-way or 2-way ANOVA, where appropriate, with Bonferroni post-hoc correction. Co-housing significantly affected gut microbiota composition, illustrated by clustering in PCoA (unweighted UniFrac distance) of co-housed mice but not their single-housed counterparts, on both HFD and LFD. The taxa driving these differences were primarily from Lachnospiraceae and Ruminococcaceae families. Single-housed WT had lower hepatic weight, TAG, cholesterol levels and Fasn despite HFD, an effect lost in their co-housed counterparts, who aligned more to IL-1RI-/- hepatic lipid status. Hepatic Cpt1α was lowest in co-housed WT. Adipose from IL-1RI-/- groups on HFD displayed increased adipocyte size and reduced adipocyte number compared to WT groups, but greater lipogenic potential (Pparg, Scd1, Dgat2) alongside a blunted IL-6 response to pro-inflammatory stimuli (~32%, P = 0.025). Whilst caecal SCFA concentrations were not different between groups, single-housed IL-1RI-/- adipocytes showed greatest sensitivity to SCFA-induced lipogenesis. Interestingly, differences in tissue functionality and gut microbiome occurred despite unaltered glucose tolerance; although there was a trend for phenotypic transfer of body weight via co-housing. For all endpoints examined, similar genotype/co-housing effects were observed for both HFD and LFD with the greatest impacts seen in HFD-fed mice. In conclusion, while the gut microbiome may be an important consideration in dietary interventions, these results question the magnitude of its impact in relation to the IL-1RI-dependent immunometabolism-glucose homeostasis axis.
β-glucans are naturally occurring polysaccharides which have isoform specific immunomodulatory and metabolic properties(1). Certain yeast (1→3)-β-D-glucan isoforms improve cholesterol(2), glucose(3) and lipid homeostasis(4). Feeding (1→3)-β-D-glucan alters the microbiome of high-fat diet (HFD) induced obese (DIO)/type 2 diabetic (T2D) mice(5). Here we investigated the potential impact of baker's yeast (1→3)-β-D-glucan in mice humanized with gut microbiomes from either obese healthy versus obese diabetic subjects on immune-metabolism within the context of high-fat feeding.
C57Bl/6J male mice received an antibiotic cocktail of Ampicillin, Metronidazole, Vancomycin, Imipenem and Ciprofloxacin HCl in their drinking water for 6 weeks to diminish the endogenous gut microbiota. Mice were inoculated with microbiota samples obtained from obese healthy (OBH) or diabetic (OBD) humans twice daily for 3 days by oral dosing. Mice were fed a low-fat diet (LFD) (10% kcal) for 4 weeks followed by HFD (45% kcal) with/without baker's yeast (1→3)-β-D-glucan (βG), for 9 weeks. Weight, feed intake, glucose tolerance (1.5g/kg), insulin tolerance (0.5U/kg), hepatic and skeletal lipid levels were examined. Tissue specific molecular markers of metabolism and inflammation, and gut microbiome analysis are being determined to compliment the phenotypic data.
OBH mice were more glucose tolerant and insulin sensitive than OBD mice, despite equal weight gain and adipose tissue mass. Fasting HOMA-IR, attributable to higher insulin concentrations, was higher in OBD compared to OBH mice. βG supplementation reduced HOMA-IR in OBD mice (P < 0.0611). Hepatic triacylglycerol (TAG) and cholesterol levels were also higher in OBD mice, which were prevented by βG supplementation. Hepatic proteomic, caecal microbiomic and metabolomic analysis is on-going in order to ascertain the impact of the OBD versus OBH dysbosis with/without βG supplementation with specific attention on immune-metabolism.
Research on the cities of the Classical Greek world has traditionally focused on mapping the organisation of urban space and studying major civic or religious buildings. More recently, newer techniques such as field survey and geophysical survey have facilitated exploration of the extent and character of larger areas within urban settlements, raising questions about economic processes. At the same time, detailed analysis of residential buildings has also supported a change of emphasis towards understanding some of the functional and social aspects of the built environment as well as purely formal ones. This article argues for the advantages of analysing Greek cities using a multidisciplinary, multi-scalar framework which encompasses all of these various approaches and adds to them other analytical techniques (particularly micro-archaeology). We suggest that this strategy can lead towards a more holistic view of a city, not only as a physical place, but also as a dynamic community, revealing its origins, development and patterns of social and economic activity. Our argument is made with reference to the research design, methodology and results of the first three seasons of fieldwork at the city of Olynthos, carried out by the Olynthos Project.
Fifty years ago Edmund Gosse observed: “We should know little or nothing of what happened to Congreve between 1700 and 1710 if it were not for the Keally letters.” The further statement must be made that in over two hundred years little or nothing has been discovered concerning the friend to whom those letters were addressed. Gosse knew only that Joseph Keally was of “Keally Mount, Kilkenny” and that he was “a relative of Bishop Berkeley.” Congreve's recent biographer, Mr. D. Crane Taylor, unaware of Keally's early death, deplores the “most regrettable” loss of letters later in date than those of Berkeley's Relics but concludes that Congreve and Keally “unquestionably remained close friends.”
Among the shadowy figures that make up the circle of Congreve's most intimate friends, Henrietta, Duchess of Marlborough, seems to have suffered most from the gossip of her own age and from the more detached but still biassed estimates of later critics. Not one of her contemporaries spoke a really decisive word in her favor; and the biographers of Congreve have preferred to dismiss her as an amusing eccentric. But one critic, Leigh Hunt, has cared to linger over this minor portrait, commenting on “the slow yet sensitive mind” of the Duchess and concluding that she loved Congreve “with all the heart she had, and a great deal of obstinacy.”
In a recent article on “The Sources of the Restoration Heroic Play,” Mr. William S. Clark discusses Elizabethan and French influences on heroic drama and supports the claim made by Sir Walter Scott, a century ago, that the heroic plays must be regarded as “the legitimate offspring” of the French heroic romances. Concerning the English influence, Mr. Clark observes: “In the face of this extensive dependence upon French suggestions the resemblances between the heroic plays and the English drama of earlier periods come to have much less significance.” Indeed, he regards as erroneous the opinion of scholars who have maintained that earlier English drama influenced “to a large degree” the heroic drama of the Restoration.
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