Metallo‐supramolecular self‐assembly tends to be performed with single metal ions and single, highly symmetrical, ligands. This simplifies the self‐assembly process as without sufficient bias within ...the system a mixture of products may be formed. However, with various applications of metallo‐supramolecular species having been demonstrated, the ability to generate more intricate architectures is keenly sought after. The use of reduced symmetry ligands is one route to this goal, and allows access to lower‐symmetry assemblies. Multiple coordination pockets can also be introduced in this manner, giving rise to assemblies with metal ions in different coordination environments, which can be exploited for the controlled synthesis of mixed‐metal species. Herein we discuss the different approaches that have been used to control self‐assembly with low symmetry ligands, including the use of mixed‐denticity ligands, the incorporation of geometric constraints, charge separation strategies and the use of repulsive or attractive non‐covalent interactions between ligands.
The highs and the lows: Spectacular advances have been made in metallo‐supramolecular chemistry over the last few decades. However, the vast majority of complexes are still assembled from highly symmetrical ligands. In this Review, the key strategies that are used to control the self‐assembly of low‐symmetry ligands with metal ions in the formation of metallo‐macrocycles and cages are summarized and emphasized with salient examples from the literature.
Fecal and serologic biomarkers can be used in the diagnosis and management of inflammatory bowel disease (IBD). Fecal markers such as calprotectin and lactoferrin have been studied for their ability ...to identify patients with IBD, assess disease activity, and predict relapse. Antibodies against Saccharomyces cerevisiae and perinuclear antineutrophil cytoplasmic proteins have been used in diagnosis of IBD, to distinguish Crohn's disease (CD) from ulcerative colitis, and to predict the risk of complications of CD. Tests for C-reactive protein and erythrocyte sedimentation rate have been used to assess inflammatory processes and predict the course of IBD progression. Levels of drug metabolites and antibodies against therapeutic agents might be measured to determine why patients do not respond to therapy and to select alternative treatments. This review addresses the potential for biomarker assays to improve treatment strategies and challenges to their use and development.
The most common question asked by patients with inflammatory bowel disease (IBD) is, “Doctor, what should I eat?” Findings from epidemiology studies have indicated that diets high in animal fat and ...low in fruits and vegetables are the most common pattern associated with an increased risk of IBD. Low levels of vitamin D also appear to be a risk factor for IBD. In murine models, diets high in fat, especially saturated animal fats, also increase inflammation, whereas supplementation with omega 3 long-chain fatty acids protect against intestinal inflammation. Unfortunately, omega 3 supplements have not been shown to decrease the risk of relapse in patients with Crohn's disease. Dietary intervention studies have shown that enteral therapy, with defined formula diets, helps children with Crohn's disease and reduces inflammation and dysbiosis. Although fiber supplements have not been shown definitively to benefit patients with IBD, soluble fiber is the best way to generate short-chain fatty acids such as butyrate, which has anti-inflammatory effects. Addition of vitamin D and curcumin has been shown to increase the efficacy of IBD therapy. There is compelling evidence from animal models that emulsifiers in processed foods increase risk for IBD. We discuss current knowledge about popular diets, including the specific carbohydrate diet and diet low in fermentable oligo-, di-, and monosaccharides and polyols. We present findings from clinical and basic science studies to help gastroenterologists navigate diet as it relates to the management of IBD.
Abnormal composition of intestinal bacteria—“dysbiosis”—is characteristic of Crohn’s disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ...ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn’s disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.
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•Inflammation, antibiotics, and diet independently affect microbiota in Crohn’s disease•Antibiotics are associated with bacterial dysbiosis and increased fungi•Dysbiosis decreases with reduction in intestinal inflammation•Diet has an independent and rapid effect on gut microbiota composition
Intestinal microbiota dysbiosis is characteristic of Crohn’s disease, but the contributing factors remain unclear. By examining pediatric Crohn’s disease patients, Lewis et al. show that dysbiosis is independently associated with antibiotics, inflammation, and diet and decreases with reduced intestinal inflammation. These results may facilitate biomarker discovery and therapeutic interventions.
Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity and sensitivity, whilst ...being non-invasive, and suitable for real-time analysis of living systems. With this perspective we highlight sensing mechanisms including Förster resonance energy transfer (FRET), intramolecular charge transfer (ICT), photoinduced electron transfer (PeT), excited state intramolecular proton transfer (ESIPT), aggregation induced emission (AIE) and multiple modality fluorescence approaches including dual/triple sensing mechanisms (DSM or TSM). Throughout the perspective we highlight the remaining challenges and suggest potential directions for development towards improved small-molecule fluorescent probes suitable for biosensing.
Small-molecule based fluorescent probes are increasingly important for the detection and imaging of biological signaling molecules due to their simplicity, high selectivity and sensitivity, whilst being non-invasive, and suitable for real-time analysis of living systems.
Diet influences health as a source of nutrients and toxins, and by shaping the composition of resident microbial populations. Previous studies have begun to map out associations between diet and the ...bacteria and viruses of the human gut microbiome. Here we investigate associations of diet with fungal and archaeal populations, taking advantage of samples from 98 well-characterized individuals. Diet was quantified using inventories scoring both long-term and recent diet, and archaea and fungi were characterized by deep sequencing of marker genes in DNA purified from stool. For fungi, we found 66 genera, with generally mutually exclusive presence of either the phyla Ascomycota or Basiodiomycota. For archaea, Methanobrevibacter was the most prevalent genus, present in 30% of samples. Several other archaeal genera were detected in lower abundance and frequency. Myriad associations were detected for fungi and archaea with diet, with each other, and with bacterial lineages. Methanobrevibacter and Candida were positively associated with diets high in carbohydrates, but negatively with diets high in amino acids, protein, and fatty acids. A previous study emphasized that bacterial population structure was associated primarily with long-term diet, but high Candida abundance was most strongly associated with the recent consumption of carbohydrates. Methobrevibacter abundance was associated with both long term and recent consumption of carbohydrates. These results confirm earlier targeted studies and provide a host of new associations to consider in modeling the effects of diet on the gut microbiome and human health.
Although averaging is effective in reducing noise, its efficiency rapidly decreases beyond several hundred averages. Depending on environmental and patient noise levels, several hundred averages may ...be insufficient for informed clinical decision making. The predictable nature of the otoacoustic emission (OAE) and noise during time-synchronous averaging implicates the use of predictive modeling as an alternative to increased averaging when noise is high. Click-evoked OAEs were measured in 98, normal-hearing subjects. Average OAE and noise levels were calculated for subsets of the total number of averages and then fit using variants of a power function. The accuracy of the models was quantified as the difference between the measured value and model output. Models were used to predict the OAE signal-to-noise ratio (SNR) for a criterion noise level. Based on predictions, the OAE was categorized as present or absent. Model-based decisions were compared to decisions from direct measurements. Model accuracy improved as the number of averages (and SNR in the case of OAEs) from which the model was derived increased. Model-based classifications permitted correct categorization of the OAE status from fewer averages than measurement-based classifications. Furthermore, model-based predictions resulted in fewer false positives (i.e., absent OAE despite normal hearing).
Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn’s disease) are abdominal pain, diarrhea, and weight loss. It is therefore not ...surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients, and among the most difficult to answer for clinicians. There are substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Additional challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD; these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, and more sustainable exclusion diets could be used to maintain long-term remission.
Antibiotic use in humans has been associated with outgrowth of fungi. Here we used a murine model to investigate the gut microbiome over 76 days of treatment with vancomycin, ampicillin, neomycin, ...and metronidazole and subsequent recovery. Mouse stool was studied as a surrogate for the microbiota of the lower gastrointestinal tract. The abundance of fungi and bacteria was measured using quantitative PCR, and the proportional composition of the communities quantified using 454/Roche pyrosequencing of rRNA gene tags. Prior to treatment, bacteria outnumbered fungi by >3 orders of magnitude. Upon antibiotic treatment, bacteria dropped in abundance >3 orders of magnitude, so that the predominant 16S sequences detected became transients derived from food. Upon cessation of treatment, bacterial communities mostly returned to their previous numbers and types after 8 weeks, though communities remained detectably different from untreated controls. Fungal communities varied substantially over time, even in the untreated controls. Separate cages within the same treatment group showed radical differences, but mice within a cage generally behaved similarly. Fungi increased ∼40-fold in abundance upon antibiotic treatment but declined back to their original abundance after cessation of treatment. At the last time point, Candida remained more abundant than prior to treatment. These data show that 1) gut fungal populations change radically during normal mouse husbandry, 2) fungi grow out in the gut upon suppression of bacterial communities with antibiotics, and 3) perturbations due to antibiotics persist long term in both the fungal and bacterial microbiota.
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