Search

In this article, we use the case of Hurricane Dorian, which hit the southeastern United States in 2019, to expand on the scholarship about professional vision by taking up how weather is materialized in the negotiation of seeing between members of the scientific community and the state. Attending to the controversy known popularly as Sharpiegate, in which President Donald Trump, the National Weather Service (NWS) office in Birmingham (Alabama) and the National Oceanic and Atmospheric Administration (NOAA) offered conflicting accounts of Hurricane Dorian’s predicted path, we use discourse analysis to examine four tweets, a NOAA official statement and the Commerce Department’s investigative report to show how institutional actors negotiated their entitlement to see, accounts of what was seen and accountability to their claims as seers. We argue that Sharpiegate significantly disrupted the relationship between science and the state, which depends upon scientists’ professional re-semiotizing of hurricanes in images which the state can use to legitimize its crisis response. Our findings show how NOAA and the Commerce Department utilize strategic ambiguity, distributed agency and accountability and the careful maintenance of boundaries in their claims of what was seen and what counts as legitimate seeing in weather forecasting.

Bimolecular excited-state proton-coupled electron transfer (PCET*) was observed for reaction of the triplet MLCT state of [(dpab)₂Ru(4,4′-dhbpy)]²⁺ (dpab = 4,4′-di(n-propyl)amido-2,2′-bipyridine, 4,4′-dhbpy = 4,4′-dihydroxy-2,2′-bipyridine) with N-methyl-4,4′-bipyridinium (MQ⁺) and N-benzyl-4,4′-bipyridinium (BMQ⁺) in dry acetonitrile solutions. The PCET* reaction products, the oxidized and deprotonated Ru complex, and the reduced protonated MQ+ can be distinguished from the excited state electron transfer (ET*) and the excited state proton transfer (PT*) products by the difference in the visible absorption spectrum of the species emerging from the encounter complex. The observed behavior differs from that of reaction of the MLCT state of [(bpy)₂Ru(4,4′-dhbpy)]²⁺ (bpy = 2,2′-bipyridine) with MQ⁺, where initial ET* is followed by diffusion-limited proton transfer from the coordinated 4,4′-dhbpy to MQ⁰. The difference in observed behavior can be rationalized based on changes in the free energies of ET* and PT*. Substitution of bpy with dpab results in the ET* process becoming significantly more endergonic and the PT* reaction becoming somewhat less endergonic.

Gut microbes have been associated with a wide variety of normal host functions as well as the development of diseases, including autoimmune, metabolic, and even neurological disorders. These relationships stem from complex host–microbe interactions originating in the gut that extend to distal regions of the body. The goal of this chapter is to provide an overview of gut microbe-mediated regulation of host nutrient digestion, absorption, and whole-body metabolism. We begin with a review of the literature evaluating the overall effects of obesity and westernized diets on the gut microbiota and how the resultant microbiota feeds forward on influencing host digestion and absorption in the gut. The latter part of the chapter will focus on how the gut microbiota regulates metabolism on a global scale influencing peripheral metabolic organs, including the liver, adipose tissue, and muscle. Altogether, this chapter highlights the mechanisms by which gut microbes regulate metabolism both locally in the gut and distally in metabolic tissues.

Metabolic diseases continue to afflict most of the U.S. population. Advancements in gut microbiota research have led to the discovery of various functional roles of microorganisms that influence the development of obesity and co-morbidities including type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease. Many mechanisms behind these host-microbe interactions stem from processes involving the intestinal epithelium including lipid metabolism. Thus, the purpose of this review is to discuss gut microbe-mediated changes in intestinal physiology and lipid metabolism that contribute to obesity, type 2 diabetes, non-alcoholic fatty liver disease and cardiovascular disease. Within each disease state, the causal role of bacteria in both driving disease development and protecting against metabolic disease will be discussed.

The role of gut microbes in health and disease has often been surmised from stool, which is easily sampled and rich in microbial diversity, density, and abundance. Microbial analyses of stool have been accepted as measures to determine the relationship of gut microbiomes with host health and disease, based on the belief that it represents all microbial populations throughout the gut. However, functional heterogeneity of each gastrointestinal tract (GIT) segment gives rise to regional differences in gut microbial populations. Herein, we summarize the literature regarding the microbial landscape along the rostral to caudal, i.e., horizontal mouth to anus, axis of the GIT. We aim to identify gaps in the literature, particularly regarding small intestinal microbiota abundance and diversity, highlight the importance of regional microbiota on host health and disease, as well as discuss opportunities to advance this line of research.

The mechanisms linking the function of microbes to host health are becoming better defined but are not yet fully understood. One recently explored mechanism involves microbe-mediated alterations in the host epigenome. Consumption of specific dietary components such as fiber, glucosinolates, polyphenols, and dietary fat has a significant impact on gut microbiota composition and function. Microbial metabolism of these dietary components regulates important epigenetic functions that ultimately influences host health. Diet-mediated alterations in the gut microbiome regulate the substrates available for epigenetic modifications like DNA methylation or histone methylation and/or acetylation. In addition, generation of microbial metabolites such as butyrate inhibits the activity of core epigenetic enzymes like histone deacetylases (HDACs). Reciprocally, the host epigenome also influences gut microbial composition. Thus, complex interactions exist between these three factors. This review comprehensively examines the interplay between diet, gut microbes, and host epigenetics in modulating host health. Specifically, the dietary impact on gut microbiota structure and function that in-turn regulates host epigenetics is evaluated in terms of promoting protection from disease development.

The small intestinal microbiota has recently been implicated in contributing to metabolic disease. We previously demonstrated that diets rich in saturated milk fat have a particularly strong impact on the small bowel microbiota as opposed to more distal gastrointestinal (GI) regions. However, the impact of antibiotics and diet on the small bowel microbiota has not been clearly demonstrated. Thus, we sought to determine how diet and antibiotics interact in modulating the regional landscape of the gut microbiota. We conducted a study using male mice on a high fat (HF) or a low fat (LF) diet (n = 15/group) that received either water control (n = 5/diet), rifaximin, (non-absorbable broad-spectrum antibiotic; n = 5/diet) or an antibiotic cocktail consisting of metronidazole, cefoperazone, vancomycin, and neomycin (Abx cocktail; n = 5/diet). 16S rRNA sequencing was performed on mucosal scrapings collected from the small intestine and cecum, as well as on stool samples. Interestingly, antibiotics had a significant effect on community composition throughout the small intestine, cecum and stool, whereas diet significantly affected only the jejunum and cecum microbiota. The antibiotic cocktail, regardless of diet, was most effective in increasing cecum size, reducing body fat percentage, and plasma lipid levels. Altogether, this study reveals a selective and divergent regional alteration of the gut microbiota by diet and antibiotics.

Cardiovascular diseases (CVD) are the main cause of death worldwide and create a substantial financial burden. Emerging studies have begun to focus on epigenetic targets and re-establishing healthy gut microbes as therapeutic options for the treatment and prevention of CVD. Phytochemicals, commonly found in fruits and vegetables, have been shown to exert a protective effect against CVD, though their mechanisms of action remain incompletely understood. Of interest, phytochemicals such as curcumin, resveratrol and epigallocatechin gallate (EGCG) have been shown to regulate both histone acetylation and microbiome re-composition. The purpose of this review is to highlight the microbiome–epigenome axis as a therapeutic target for food bioactives in the prevention and/or treatment of CVD. Specifically, we will discuss studies that highlight how the three phytochemicals above alter histone acetylation leading to global changes in gene expression and CVD protection. Then, we will expand upon these phytochemicals to discuss the impact of phytochemical–microbiome–histone acetylation interaction in CVD.

Several experimental models demonstrate a role for gut microbiota in the progression of type 1 diabetes (T1D) in genetically prone hosts. While the association between disturbances in gut microbiota, or microbial dysbiosis, and complex immune diseases such as inflammatory bowel diseases (IBD) are well established, less is known about its role in T1D pathogenesis. In IBD-prone interleukin-10 deficient (IL-10 KO) mice, the absence of gut microbiota under germ-free (GF) conditions prevents IBD development. However, in aged GF IL-10 KO mice (>6-months of age), polyuria and pancreatic lymphocytic infiltration resembling T1D lesions was observed. Approximately 50% of male and female mice above 6-months of age develop pancreatic immune cell infiltration, as compared to none in conventionally-raised and fecal microbiota transplanted (FMT) IL-10 KO counterparts. Immunofluorescence staining of islet infiltrates was positive for adaptive and innate immunological markers, including lymphoid and myeloid cell markers, which typically characterize autoimmune T1D lesions. A subset of GF IL-10 KO mice was also positive for insulin autoantibodies (IAA), but the majority of mice did not become diabetic. Our findings of early stage lymphocytic infiltrates in the pancreas and IAA in the absence of overt diabetes in GF IL-10 KO mice embody the early stages of T1D pathogenesis. As such, we propose that the presence of gut microbiota play a protective role against immune infiltration in the pancreas of genetically prone hosts. Moreover, our model provides an opportunity to better understand the role of the microbiota in the early stages of immune pathogenesis and perhaps conceive the development of microbe-mediated prophylactic strategies to treat or even prevent T1D.

Summary: Transcriptional regulation of circadian rhythms is essential for lipid metabolic homeostasis, disruptions of which can lead to metabolic diseases. Whether N6-methyladenosine (m6A) mRNA methylation impacts circadian regulation of lipid metabolism is unclear. Here, we show m6A mRNA methylation oscillations in murine liver depend upon a functional circadian clock. Hepatic deletion of Bmal1 increases m6A mRNA methylation, particularly of PPaRα. Inhibition of m6A methylation via knockdown of m6A methyltransferase METTL3 decreases PPaRα m6A abundance and increases PPaRα mRNA lifetime and expression, reducing lipid accumulation in cells in vitro. Mechanistically, YTHDF2 binds to PPaRα to mediate its mRNA stability to regulate lipid metabolism. Induction of reactive oxygen species both in vitro and in vivo increases PPaRα transcript m6A levels, revealing a possible mechanism for circadian disruption on m6A mRNA methylation. These data show that m6A RNA methylation is important for circadian regulation of downstream genes and lipid metabolism, impacting metabolic outcomes. : Zhong et al. reveal that hepatic Bmal1 deletion changes m6A mRNA methylation, particularly of PPaRα. METTL3 or YTHDF2 knockdown affects PPaRα transcription and translation, impacting downstream lipid metabolism. These findings further reveal the overlap between circadian gene network disruption, mRNA m6A modifications, and metabolic state. Keywords: circadian clock, Bmal1, hepatic, lipid metabolism, ROS, m6A RNA methylation, post-transcriptional regulation, METTL3, YTHDF2, PPaRα

Our recently published paper “Small Intestine Microbiota Regulate Digestive and Absorptive Adaptive Responses to Dietary Lipids” in Cell Host & Microbe explored the neglected small intestine microbiota and demonstrated its critical role as a regulator of fat digestion and absorption. This work generated the following important take home messages: 1) small intestinal microbes are particularly sensitive to high fat diets and turn on host processes regulating fat digestion and transport, 2) this action is very likely orchestrated by a consortium of microbes, each having different specific effects and targets, and 3) the actions of this consortium appear to be mediated by bacteria-derived small molecules or bioactive components. These findings are expected to provide insight into developing treatments for conditions of under- or over-nutrition. The goal of this addendum is to summarize our findings, address issues related to gut microbiota and gnotobiotic research specifically regarding technology and experimental design, discuss this work in the context of relevant literature, and lastly provide considerations for future research.

This manuscript reports the reaction of the 3MLCT excited states of two luminescent chromophores, [(bpy)2Ru(OHbpy)]2+ and [(bpy)2Ru(OMebpy)]2+ (bpy = 2,2′-bipyridine, OHbpy = 4-hydroxy-2,2′-bipyridine, OMebpy = 4-methoxy-2,2′-bipyridine), with anthraquinone (AQ). A series of luminescence, electrochemical, spectrophotometric and transient absorption studies were done in order to determine free energies for the potential reaction paths between the photoexcited complexes and AQ. For the OMebpy complex, only excited state electron transfer (ET*) from the 3MLCT state of the complex to AQ was possible. However, for the OHbpy complex, the excited state could react with AQ via a variety of pathways including excited state electron transfer, ET*, excited state proton transfer (PT*) and excited state proton coupled electron transfer (PCET*). The thermodynamic analysis revealed that, for the OHbpy complex PT* was very endergonic and not a viable reaction pathway, however both ET* and PCET* could occur. Luminescence quenching studies revealed that both the OHbpy and the OMebpy excited complexes reacted with AQ (kq ~ 109 M−1s−1 for both). Transient absorption analysis showed that, for the OMebpy complex, no photoproducts escaped the encounter complex associated with the quenching reaction. The result is consistent with strong electrostatic association of the 3+/1- encounter complex. For the OHbpy complex transient absorption results clearly show the formation of PCET* products from the encounter complex. The result represents one of a small number of examples of excited states of chromophores reacting via proton coupled electron transfer within an encounter complex.

fac -(bpy)Re(CO) 3 CF 3 SO 3 reacts with sodium dicyanamide in THF/MeOH/H 2 O to give fac -(bpy)Re(CO) 3 N(CN) 2 ( 1 ) in 81% yield. Complex 1 was characterized spectroscopically and electrochemically using NMR, IR, UV–Vis, fluorescence and cyclic voltammetry. Complex 1 crystallizes in the P2 1 /c space group with a = 7.2004(3) A, b = 12.9547(5) A, c = 16.8523(6) A, β = 101.989(1) °, and Z = 4. Photophysical measurements indicate the π-acceptor ability of N(CN) 2 − as equivalent to that of the 4- N , N -dimethylaminopyridine ligand. Strong luminescence is observed in solution at room temperature and in 4:1 ethanol:methanol matrices at 77 K attributed to the 3 MLCT state.

The scope of direct substitution of the dithiolene ligand from [M(S2C2Ph2)2] [M = Ni2+ (1), Pd2+ (2), Pt2+ (3)] to produce heteroleptic species [M(S2C2Ph2)2Ln] (n = 1, 2) has been broadened to include isonitriles and dithiooxamides in addition to phosphines and diimines. Collective observations regarding ligands that cleanly produce [M(S2C2Ph2)Ln], do not react at all, or lead to ill-defined decomposition identify soft σ donors as the ligand type capable of dithiolene substitution. Substitution of MeNC from [Ni(S2C2Ph2)(CNMe)2] by L provides access to a variety of heteroleptic dithiolene complexes not accessible from 1. Substitution of a dithiolene ligand from 1 involves net redox disproportionation of the ligands from radical monoanions, –S•SC2Ph2, to enedithiolate and dithione, the latter of which is an enhanced leaving group that is subject to further irreversible reactions.

Obesity afflicts 36.5% of the US population and 600 million individuals world-wide. Thus, it is imperative to understand the risk factors underlying metabolic disease including diet, activity level, sleep, and genetics. Another key contributory factor is the gut microbiota given its widely reported role in the development of metabolic disease. The gut microbiota, particularly its structure and function, is heavily influenced by Western style diets rich in a complex mixture of fats and high in simple sugars. In this review, the profound impact of obesity and Western diets on the gut microbiota will be illustrated, and the following research questions will be addressed: 1) to what extent do high fat diets (HFDs) alter community membership and function and does this depend upon the amount or type of fat consumed?, 2) how rapidly do dietary shifts alter gut microbial communities?, 3) are these alterations sustained or can the microbiome recover from dietary stress?, 4) how does diet drive host-microbe interactions leading to obesity?, and 5) what can be done to restore the detrimental impact of HFD on the gut microbiota? The goal of this review is to address these questions by parsing out the effects and underlying mechanisms of how Western diets impact the gut microbiota and host. By doing so, potential avenues for further exploration and strategies for microbiome-based interventions to prevent or treat diet-induced obesity may become more apparent.

Obesity is an emerging global epidemic with profound challenges to world health care economies and societies. Traditional approaches to fighting obesity have not shown promise in promoting a decline in obesity prevalence. The gut microbiota is becoming widely appreciated for its role in regulating metabolism and thus represents a target for new therapies to combat obesity and associated comorbidities. This article provides an overview of altered microbial community structure in obesity, dietary impact on the gut microbiota, host-microbe interactions contributing to the disease, and improvements in microbial assemblage after bariatric surgery and with therapies targeting the gut microbiome.

This chapter introduces the link between diet, gut microbiota, and host epigenetics. Environmental cues including diet and gut microbiota trigger epigenetic modifications that regulate gene expression, influencing disease progression. Diet-microbe interactions have been shown to influence (1) available substrates for epigenetic modification (i.e., methyl and acetyl groups), (2) DNA methylation or histone methylation and/or acetylation, and (3) the generation of microbial metabolites that regulate the activity of epigenetic proteins such as histone deacetylases (HDACs). Conversely, the epigenome of the host also influences gut microbial composition. The goal of this chapter is to summarize current literature showing that alterations in dietary intake significantly influence the gut microbiota that, in turn, modifies the epigenome, having significant consequences on host health. Advancements in this research area are expected to lead to the prevention and/or treatment of diseases caused, at least in-part, by these diet-microbiome-host epigenome interactions.

The gut microbiota affects intestinal permeability and mucosal mast cells (MMCs) responses. Activation of MMCs has been associated with absorption of dietary fat. We investigated whether the gut microbiota contributes to the fat-induced activation of MMCs in rats, and how antibiotics might affect this process.Adult male Sprague-Dawley rats were given streptomycin and penicillin for 4 days (n = 6-8) to reduce the abundance of their gut flora, or normal drinking water (controls, n = 6-8). They underwent lymph fistula surgery and after an overnight recovery were given an intraduodenal bolus of intralipid. We collected intestinal tissues and lymph fluid and assessed activation of MMCs, intestinal permeability, and fat transport parameters.Compared with controls, intestinal lymph from rats given antibiotics had reduced levels of mucosal mast cell protease II (produced by MMCs) and decreased activity of diamine oxidase (produced by enterocytes) (P.05). Rats given antibiotics had reduced intestinal permeability in response to dietary lipid compared with controls (P.01). Unexpectedly, antibiotics also reduced lymphatic transport of triacylglycerol and phospholipid (P.01), concomitant with decreased levels of mucosal apolipoproteins B, A-I, and A-IV (P.01). No differences were found in intestinal motility or luminal pancreatic lipase activity between rats given antibiotics and controls. These effects were not seen with an acute dose of antibiotics or 4 weeks after the antibiotic regimen ended.The intestinal microbiota appears to activate MMCs after the ingestion of fat in rats; this contributes to fat-induced intestinal permeability. We found that the gut microbiome promotes absorption of lipid, probably by intestinal production of apolipoproteins and secretion of chylomicrons.

The obesity epidemic afflicts over one third of the United States population. With few therapies available to combat obesity, a greater understanding of the systemic causes of this and other metabolic disorders is needed to develop new, effective treatments. The mammalian intestinal microbiota contributes to metabolic processes in the host. This review summarizes the research demonstrating the interplay of diet, intestinal microbiota and host metabolism. We detail the effects of diet-induced modifications in microbial activity and resultant impact on (1) sensory perception of macronutrients and total energy intake; (2) nutrient absorption, transport and storage; (3) liver and biliary function; (4) immune-mediated signaling related to adipose inflammation; and (5) circadian rhythm. We also discuss therapeutic strategies aimed to modify host-microbe interactions, including prebiotics, probiotics and postbiotics, as well as fecal microbiota transplantation. Elucidating the role of gut microbes in shaping metabolic homeostasis or dysregulation provides greater insight into disease development and a promising avenue for improved treatment of metabolic dysfunction.

Our objective was to determine if consuming table grapes reduces adiposity and its metabolic consequences and alters gut microbiota in mice fed a high fat (HF), butter-rich diet. C57BL/6J mice were fed a low fat (LF) diet or HF diet with 3% or 5% grapes for 11 weeks. Total body and inguinal fat were moderately, but significantly reduced in mice fed both levels of grapes compared to their controls. Mice fed 5% grapes had lower liver weights and triglyceride levels, and decreased expression of glycerol-3-phosphate acyltransferase (Gpat1) compared to the 5% controls. Mice fed 3% grapes had lower hepatic mRNA levels of peroxisome proliferator-activated receptor gamma 2, sterol-CoA desaturase 1, fatty-acid binding protein 4, and Gpat1 compared to the 3% controls. Although grape feeding had only a minor impact on markers of inflammation or lipogenesis in adipose tissue or intestine, 3% grapes decreased the intestinal abundance of sulfidogenic Desulfobacter spp., and the Bilophila wadsworthia-specific dissimilatory sulfite reductase gene (dsrA-Bw), and tended to increase the abundance of the beneficial bacterium Akkermansia muciniphila compared to controls. Additionally, Bifidobacterium, Lactobacillus, Allobaculum, and several other genera correlated negatively with adiposity. Allobaculum in particular was increased in the LF and 3% grapes groups compared to the HF-fed controls. Notably, grape feeding attenuated the HF-induced impairment in epithelial localization of the intestinal tight junction protein zonula occludens. Collectively, these data indicate that some of the adverse health consequences of consuming a HF diet rich in saturated fat can be attenuated by table grape consumption.

Ruthenium complexes containing a sterically congested metal center can serve as light activated prodrugs through photo-activated chemotherapy (PACT). In this work, we modified PACT agents containing 6,6′-dihydroxybipyridine (6,6′-dhbp) (Papish et al., Inorg. Chem., 2017, 56, 7519) by replacing it with a sterically bulky isoelectronic ligand, 6,6′-dimethoxybipyridine (6,6′-dmbp). The resulting complexes, [(phen)2Ru(6,6′-dmbp)]Cl2 (2OMe, phen = 1,10-phenanthroline) and [(dop)2Ru(6,6′-dmbp)]Cl2 (3OMe, dop = 2,3-dihydro-[1,4]dioxino[2,3-f][1,10]phenanthroline), have been fully characterized and display enhanced quantum yields for blue light triggered photodissociation of 0.024(6) and 0.0030(2), respectively. We have also synthesized 4OH = [(dmphen)2Ru(4,4′-dhbp)]Cl2 wherein dmphen = 2,9-dimethyl-1,10-phenanthroline and 4,4′-dhbp = 4,4′-dihydroxybipyridine. These ligands enhance steric bulk near the metal center and move the hydroxy groups further from the metal center, respectively. Complex 4OH displays a relatively low quantum yield of 0.0014(2). All of the new complexes (2OMe, 3OMe, 4OH) were tested in breast cancer cells (MDA-MB-231) and were non-toxic (IC50 > 100 μM). This has been interpreted in terms of unfavorable log(Do/w) values and furthermore photodissociation alone is insufficient for cytotoxicity. We also report the crystal structures of 4OH and 2OMe, the thermodynamic acidity of complex 4OH, and the redox potentials for all new complexes.

Murine models are widely used to explore host-microbe interactions because of the challenges and limitations inherent to human studies. However, microbiome studies in murine models are not without their nuances. Inter-individual variations in gut microbiota are frequent even in animals housed within the same room. We therefore sought to find an efficient and effective standard operating procedure (SOP) to minimize these effects to improve consistency and reproducibility in murine microbiota studies. Mice were housed in a single room under specific-pathogen free conditions. Soiled cage bedding was routinely mixed weekly and distributed among all cages from weaning (three weeks old) until the onset of the study. Females and males were separated by sex and group-housed (up to five mice/cage) at weaning. 16S rRNA gene analyses of fecal samples showed that this protocol significantly reduced pre-study variability of gut microbiota amongst animals compared to other conventional measures used to normalize microbiota when large experimental cohorts have been required. A significant and consistent effect size was observed in gut microbiota when mice were switched from regular chow to purified diet in both sexes. However, sex and aging appeared to be independent drivers of gut microbial assemblage and should be taken into account in studies of this nature. In summary, we report a practical and effective pre-study SOP for normalizing the gut microbiome of murine cohorts that minimizes inter-individual variability and resolves co-housing problems inherent to male mice. This SOP may increase quality, rigor, and reproducibility of data acquisition and analysis.

Advances in high-throughput sequencing have facilitated remarkable insights into the diversity and functioning of naturally occurring microbes; however, current sequencing strategies are insufficient to reveal physiological states of microbial communities associated with protein translation dynamics. Transfer RNAs (tRNAs) are core components of protein synthesis machinery, present in all living cells, and are phylogenetically tractable, which make them ideal targets to gain physiological insights into environmental microbes. Here we report a direct sequencing approach, tRNA-seq, and a software suite, tRNA-seq-tools, to recover sequences, abundance profiles, and post-transcriptional modifications of microbial tRNA transcripts. Our analysis of cecal samples using tRNA-seq distinguishes high-fat- and low-fat-fed mice in a comparable fashion to 16S ribosomal RNA gene amplicons, and reveals taxon- and diet-dependent variations in tRNA modifications. Our results provide taxon-specific in situ insights into the dynamics of tRNA gene expression and post-transcriptional modifications within complex environmental microbiomes., The authors present a molecular approach and a software suite for high-throughput sequencing and characterization of microbial tRNA transcripts, which provide unique physiological insights into complex environmental microbes.

The scope of direct substitution of the dithiolene ligand from [M(S

The gut microbiota has been implicated in the development of a number of chronic gastrointestinal and systemic diseases. These include inflammatory bowel diseases, irritable bowel syndrome, and metabolic (i.e. obesity, non-alcoholic fatty liver disease, and diabetes) and neurological diseases. The advanced understanding of host-microbe interactions has largely been due to new technologies such as 16S rRNA sequencing to identify previously unknown microbial communities and, more importantly, their functional characteristics through metagenomic sequencing and other multi-omic technologies, such as metatranscriptomics, metaproteomics, and metabolomics. Given the vast array of newly acquired knowledge in the field and technological advances, it is expected that mechanisms underlying several disease states involving the interactions between microbes, their metabolites, and the host will be discovered. The identification of these mechanisms will allow for the development of more precise therapies to prevent or manage chronic disease. This review discusses the functional characterization of the microbiome, highlighting the advances in identifying bioactive microbial metabolites that have been directly linked to gastrointestinal and peripheral diseases.

Altering the gut microbiome with prebiotics can mitigate dysbiosis and improve intestinal and systemic health. Plants are rich in three main classes of polyphenols with prebiotic properties: (1) phenolics acids, (2) flavonoids, and (3) other phenolics. All of these are abundant in fruits, vegetables, spices, and herbs and have both antioxidant and antiinflammatory properties. Because dietary polyphenols are poorly absorbed in the small intestine, they persist in the colon to be metabolized into aromatic metabolites that are absorbed into the portal blood and sent to the liver or excreted in the feces. Hepatic polyphenol metabolites enter the (1) bloodstream for uptake by target tissues, (2) bladder for urinary excretion, or (3) bile acid pool for remixing with intestinal digesta. In the colon, polyphenols alter the populations of gut microbes and the production of microbial metabolites and host-derived intestinal metabolites and peptide hormones that influence intestinal integrity and systemic metabolism.

We have demonstrated that trans-10, cis-12 conjugated linoleic acid (18:2t10,c12)-mediated delipidation of human adipocytes was dependent on increased intracellular calcium and activation of inflammatory signaling in human primary adipocytes. These data are consistent with the actions of diacylglycerol and inositol triphosphate derived from phospholipase C (PLC)-dependent cell signaling. To test the hypothesis that PLC was an upstream activator of these cellular responses to 18:2t10,c12, primary cultures of human adipocytes were pretreated with 1-[6-((17β-3-methoxyestra-1,3,5 (10)-trien-17-yl)amino)hexyl]-1H-pyrrole-2,5-dione ({"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122), a universal PLC inhibitor, followed by 18:2t10,c12 treatment. {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 attenuated 18:2t10,c12-mediated insulin resistance within 48 h and suppression of the mRNA levels of peroxisome proliferator-activated receptor (PPAR)γ, insulin-stimulated glucose transporter-4, acetyl-CoA carboxylase-1, and stearoyl-CoA desaturase-1, and the protein levels of PPARγ within 18–24 h. {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122 inhibited 18:2t10,c12-mediated induction of the inflammatory-related genes calcium/calmodulin-dependent protein kinase-β, cyclooxygenase-2, monocyte chemoattractant protein-1, interleukin (IL)-6, and IL-8, secretion of IL-6 and IL-8, and the activation of extracellular signal-related kinase, c-Jun N-terminal kinase, and c-Jun within 18–24 h. Moreover, 18:2t10,c12 increased the mRNA levels of heat shock proteins within 6–24 h and intracellular calcium concentrations within 3 min, which were inhibited by {"type":"entrez-nucleotide","attrs":{"text":"U73122","term_id":"4098075","term_text":"U73122"}}U73122. Lastly, 18:2t10,c12 increased the abundance of PLCγ1 in the plasma membrane within 3 min. Taken together, these data suggest that PLC plays an important role in 18:2t10,c12-mediated activation of intracellular calcium accumulation, inflammatory signaling, delipidation, and insulin resistance in human primary adipocytes.

The objective of this study was to examine the mechanism by which conjugated linoleic acid (CLA) reduces body fat. Young male mice were fed three combinations of fatty acids at three doses (0.06%, 0.2%, and 0.6%, w/w) incorporated into AIN76 diets for 7 weeks. The types of fatty acids were linoleic acid (control), an equal mixture of trans-10, cis-12 (10,12) CLA plus linoleic acid, and an equal isomer mixture of 10,12 plus cis-9, trans-11 (9,11) CLA. Mice receiving the 0.2% and 0.6% dose of 10,12 CLA plus linoleic acid or the CLA isomer mixture had decreased white adipose tissue (WAT) and brown adipose tissue (BAT) mass and increased incorporation of CLA isomers in epididymal WAT and liver. Notably, in mice receiving 0.2% of both CLA treatments, the mRNA levels of genes associated with browning, including uncoupling protein 1 (UCP1), UCP1 protein levels, and cytochrome c oxidase activity, were increased in epididymal WAT. CLA-induced browning in WAT was accompanied by increases in mRNA levels of markers of inflammation. Muscle cytochrome c oxidase activity and BAT UCP1 protein levels were not affected by CLA treatment. These data suggest a linkage between decreased adiposity, browning in WAT, and low-grade inflammation due to consumption of 10,12 CLA.

The metabolic benefits induced by gastric bypass, currently the most effective treatment for morbid obesity, are associated with bile acid (BA) delivery to the distal intestine. However, mechanistic insights into BA signaling in the mediation of metabolic benefits remain an area of study. The bile diversion () mouse model, in which the gallbladder is anastomosed to the distal jejunum, was used to test the specific role of BA in the regulation of glucose and lipid homeostasis. Metabolic phenotype, including body weight and composition, glucose tolerance, energy expenditure, thermogenesis genes, total BA and BA composition in the circulation and portal vein, and gut microbiota were examined. BD improves the metabolic phenotype, which is in accord with increased circulating primary BAs and regulation of enterohormones. BD-induced hypertrophy of the proximal intestine in the absence of BA was reversed by BA oral gavage, but without influencing BD metabolic benefits. BD-enhanced energy expenditure was associated with elevated TGR5, D2, and thermogenic genes, including UCP1, PRDM16, PGC-1α, PGC-1β, and PDGFRα in epididymal white adipose tissue (WAT) and inguinal WAT, but not in brown adipose tissue. BD resulted in an altered gut microbiota profile (i.e., Firmicutes bacteria were decreased, Bacteroidetes were increased, and Akkermansia was positively correlated with higher levels of circulating primary BAs). Our study demonstrates that enhancement of BA signaling regulates glucose and lipid homeostasis, promotes thermogenesis, and modulates the gut microbiota, which collectively resulted in an improved metabolic phenotype.

The anti-inflammatory, antioxidant, or antimicrobial properties of phytochemicals found in fruits and vegetables are well documented. Phytoactive compounds and their metabolites have typically been monitored in blood or non-intestinal tissues of animals or human subjects consuming whole foods, extracts, or individual phytochemicals or examined after phytochemical treatment of cells in culture. Much less is known about the influence of polyphenols, in particular those found in grapes (e.g., anthocyanins), on intestinal health and how these polyphenols indirectly influence systemic metabolism. Notably, polyphenols may influence nutrient digestion and absorption, and gut microbiota taxa and their fermentation products, in part, because they are poorly absorbed in the upper gut and thus persist in the colon. Here, they come in direct contact with microbes, influencing microbial growth and metabolism, as well as undergoing enzymatic modification based on the available microbes. Whereas a great deal is known about the fermentation of fiber, there are gaps in the literature concerning how polyphenols influence microbial metabolism and vice versa. Therefore, this paper will focus on studies examining the influence of polyphenols in general and grape polyphenols in particular, on intestinal health, and subsequent metabolic consequences.

The weight loss supplement conjugated linoleic acid (CLA) consists of an equal mixture of trans-10, cis-12 (10,12) and cis-9, trans-11 (9,11) isomers. However, high levels of mixed CLA isomers, or the 10,12 isomer, causes chronic inflammation, lipodystrophy, or insulin resistance. We previously demonstrated that 10,12 CLA decreases de novo lipid synthesis along with the abundance and activity of stearoyl-CoA desaturase (SCD)-1, a delta-9 desaturase essential for the synthesis of monounsaturated fatty acids (MUFA). Thus, we hypothesized that the 10,12 CLA-mediated decrease in SCD-1, with the subsequent decrease in MUFA, was responsible for the observed effects. To test this hypothesis, 10,12 CLA-treated human adipocytes were supplemented with oleic acid for 12 h to 7 d, and inflammatory gene expression, insulin-stimulated glucose uptake, and lipid content were measured. Oleic acid reduced inflammatory gene expression in a dose-dependent manner, and restored the lipid content of 10,12 CLA-treated adipocytes without improving insulin-stimulated glucose uptake. In contrast, supplementation with stearic acid, a substrate for SCD-1, or 9,11 CLA did not prevent inflammatory gene expression by 10,12 CLA. Notably, 10,12 CLA impacted the expression of several G-protein coupled receptors that was attenuated by oleic acid. Collectively, these data show that oleic acid attenuates 10,12 CLA-induced inflammatory gene expression and lipid content, possibly by alleviating cell stress caused by the inhibition of MUFA needed for phospholipid and neutral lipid synthesis.

Conjugated linoleic acid (CLA) reduces adiposity in vivo. However, mechanisms mediating these changes are unclear. Therefore, we treated cultures of human adipocytes with trans-10, cis-12 (10,12) CLA, cis-9, trans-11 (9,11) CLA or other trans fatty acids (FA), and measured indices of lipid metabolism. The lipid-lowering effects of 10,12 CLA were unique, as other trans FA did not reduce TG content to the same extent. Using low levels of [(14)C]-CLA isomers, it was shown that both isomers were readily incorporated into acylglycerols and phospholipids, albeit at lower levels than [(14)C]-oleic or [(14)C]-linoleic acids. When using [(14)C]-acetic acid and [(14)C]-pyruvic acid as substrates, 30 μM 10,12 CLA, but not 9,11 CLA, decreased de novo synthesis of triglyceride, free FA, diacylglycerol, cholesterol esters, cardiolipin, phospholipids and ceramides within 3-24 h. Treatment with 30 μM 10,12 CLA, but not 9,11 CLA, decreased total cellular lipids within 3 days and the ratio of monounsaturated FA (MUFA) to saturated FA, and increased C18:0 acyl-CoA levels within 24 h. Consistent with these data, stearoyl-CoA desaturase (SCD)-1 mRNA and protein levels were down-regulated by 10,12 CLA within 7-12 h, respectively. The mRNA levels of liver X receptor (LXR)α and sterol regulatory element binding protein (SREBP)-1c, transcription factors that regulate SCD-1, were decreased by 10,12 CLA within 5 h. These data suggest that the isomer-specific decrease in de novo lipid synthesis by 10,12 CLA is due, in part, to the rapid repression of lipogenic transcription factors that regulate MUFA synthesis, suggesting an anti-obesity mechanism unique to this trans FA.

Herein, we report on changes in the performance of a commercial cellulose triacetate (CTA) membrane, imparted by varied operating conditions and solution chemistries. Changes to feed and draw solution flow rate did not significantly alter the CTA membrane's water permeability, salt permeability, or membrane structural parameter when operated with the membrane skin layer facing the draw solution (PRO-mode). However, water and salt permeability increased with increasing feed or draw solution temperature, while the membrane structural parameter decreased with increasing draw solution, possibly due to changes in polymer intermolecular interactions. High ionic strength draw solutions may de-swell the CTA membrane via charge neutralization, which resulted in lower water permeability, higher salt permeability, and lower structural parameter. This observed trend was further exacerbated by the presence of divalent cations which tends to swell the polymer to a greater extent. Finally, the calculated CTA membrane's structural parameter was lower and less sensitive to external factors when operated in PRO-mode, but highly sensitive to the same factors when the skin layer faced the feed solution (FO-mode), presumably due to swelling/de-swelling of the saturated porous substructure by the draw solution. This is a first attempt aimed at systematically evaluating the changes in performance of the CTA membrane due to operating conditions and solution chemistry, shedding new insight into the possible advantages and disadvantages of this material in certain applications.

The telehealth initiatives of the Department of Defense (DoD) and Veterans’ Health Administration (VHA) continue to test the limits of technology to provide the best care to our service members, veterans and their families. The DoD and VHA have credentialing systems in place to allow clinical practice between facilities. New legislation in the form of the Servicemembers’ Telemedicine and E-Health Portability (STEP) Act will potentially expand telehealth clinical services across state lines into the homes of our service members and veterans.