Integrating Multiple Analytical Datasets to Compare Metabolite Profiles of Mouse Colonic-Cecal Contents and Feces.

The pattern of metabolites produced by the gut microbiome comprises a phenotype indicative of the means by which that microbiome affects the gut. We characterized that phenotype in mice by conducting metabolomic analyses of the colonic-cecal contents, comparing that to the metabolite patterns of feces in order to determine the suitability of fecal specimens as proxies for assessing the metabolic impact of the gut microbiome. We detected a total of 270 low molecular weight metabolites in colonic-cecal contents and feces by gas chromatograph, time-of-flight mass spectrometry (GC-TOF) and ultra-high performance liquid chromatography, quadrapole time-of-flight mass spectrometry (UPLC-Q-TOF). Of that number, 251 (93%) were present in both types of specimen, representing almost all known biochemical pathways related to the amino acid, carbohydrate, energy, lipid, membrane transport, nucleotide, genetic information processing, and cancer-related metabolism. A total of 115 metabolites differed significantly in relative abundance between both colonic-cecal contents and feces. These data comprise the first characterization of relationships among metabolites present in the colonic-cecal contents and feces in a healthy mouse model, and shows that feces can be a useful proxy for assessing the pattern of metabolites to which the colonic mucosum is exposed

Harmonic moment dynamics in Laplacian growth

Harmonic moments are integrals of integer powers of z = x+iy over a domain. Here the domain is an exterior of a bubble of air growing in an oil layer between two horizontal closely spaced plates. Harmonic moments are a natural basis for such Laplacian growth phenomena because, unlike other representations, these moments linearize the zero surface tension problem (Richardson, 1972), so that all moments except the lowest one are conserved in time. For non-zero surface tension, we show that the the harmonic moments decay in time rather than exhibiting the divergences of other representations. Our laboratory observations confirm the theoretical predictions and demonstrate that an interface dynamics description in terms of harmonic moments is physically realizable and robust. In addition, by extending the theory to include surface tension, we obtain from measurements of the time evolution of the harmonic moments a value for the surface tension that is within 20% of the accepted value.Comment: 10 pages, 7 figure

Feeding of fish oil and medium-chain triglycerides to canines impacts circulating structural and energetic lipids, endocannabinoids, and non-lipid metabolite profiles

IntroductionThe effect of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides from fish oil (FO), and their combination (FO+MCT) on the serum metabolome of dogs (Canis familiaris) was evaluated.MethodsDogs (N = 64) were randomized to either a control food, one with 7% MCT, one with FO (0.18% eicosapentaenoate and 1.3% docosahexaenoate), or one with FO+MCT for 28 days following a 14-day washout period on the control food. Serum metabolites were analyzed via chromatography followed by mass spectrometry.ResultsAdditive effects of serum metabolites were observed for a number of metabolite classes, including fatty acids, phospholipids, acylated amines including endocannabinoids, alpha-oxidized fatty acids, and methyl donors. Some effects of the addition of FO+MCT were different when the oils were combined compared with when each oil was fed separately, namely for acylcarnitines, omega-oxidized dicarboxylic acids, and amino acids. Several potentially beneficial effects on health were observed, including decreased circulating triglycerides and total cholesterol with the addition of FO (with or without MCT) and decreases in N-acyl taurines with the addition of MCT, FO, or FO+MCT.DiscussionOverall, the results of this study provide a phenotypic characterization of the serum lipidomic response to dietary supplementation of long-chain n3-polyunsaturated and medium-chain saturated fats in canines

Cyclin E overexpression impairs progression through mitosis by inhibiting APCCdh1

Overexpression of cyclin E, an activator of cyclin-dependent kinase 2, has been linked to human cancer. In cell culture models, the forced expression of cyclin E leads to aneuploidy and polyploidy, which is consistent with a direct role of cyclin E overexpression in tumorigenesis. In this study, we show that the overexpression of cyclin E has a direct effect on progression through the latter stages of mitotic prometaphase before the complete alignment of chromosomes at the metaphase plate. In some cases, such cells fail to divide chromosomes, resulting in polyploidy. In others, cells proceed to anaphase without the complete alignment of chromosomes. These phenotypes can be explained by an ability of overexpressed cyclin E to inhibit residual anaphase-promoting complex (APCCdh1) activity that persists as cells progress up to and through the early stages of mitosis, resulting in the abnormal accumulation of APCCdh1 substrates as cells enter mitosis. We further show that the accumulation of securin and cyclin B1 can account for the cyclin E–mediated mitotic phenotype

Programmable monodisperse glyco-multivalency using self-assembled coordination cages as scaffolds

The multivalent presentation of glycans leads to enhanced binding avidity to lectins due to the cluster glycoside effect. Most materials used as scaffolds for multivalent glycan arrays, such as polymers or nanoparticles, have intrinsic dispersity: meaning that in any sample, a range of valencies are presented and it is not possible to determine which fraction(s) are responsible for binding. The intrinsic dispersity of many multivalent glycan scaffolds also limits their reproducibility and predictability. Here we make use of the structurally programmable nature of self-assembled metal coordination cages, with polyhedral metal-ion cores supporting ligand arrays of predictable sizes, to assemble a 16-membered library of perfectly monodisperse glycoclusters displaying valencies from 2 to 24 through a careful choice of ligand/metal combinations. Mono- and trisaccharides are introduced into these clusters, showing that the synthetic route is tolerant of biologically relevant glycans, including sialic acids. The cluster series demonstrates increased binding to a range of lectins as the number of glycans increases. This strategy offers an alternative to current glycomaterials for control of the valency of three-dimensional (3-D) glycan arrays, and may find application across sensing, imaging, and basic biology

SemEHR:A general-purpose semantic search system to surface semantic data from clinical notes for tailored care, trial recruitment, and clinical research

OBJECTIVE: Unlocking the data contained within both structured and unstructured components of electronic health records (EHRs) has the potential to provide a step change in data available for secondary research use, generation of actionable medical insights, hospital management, and trial recruitment. To achieve this, we implemented SemEHR, an open source semantic search and analytics tool for EHRs. METHODS: SemEHR implements a generic information extraction (IE) and retrieval infrastructure by identifying contextualized mentions of a wide range of biomedical concepts within EHRs. Natural language processing annotations are further assembled at the patient level and extended with EHR-specific knowledge to generate a timeline for each patient. The semantic data are serviced via ontology-based search and analytics interfaces. RESULTS: SemEHR has been deployed at a number of UK hospitals, including the Clinical Record Interactive Search, an anonymized replica of the EHR of the UK South London and Maudsley National Health Service Foundation Trust, one of Europe's largest providers of mental health services. In 2 Clinical Record Interactive Search-based studies, SemEHR achieved 93% (hepatitis C) and 99% (HIV) F-measure results in identifying true positive patients. At King's College Hospital in London, as part of the CogStack program (github.com/cogstack), SemEHR is being used to recruit patients into the UK Department of Health 100 000 Genomes Project (genomicsengland.co.uk). The validation study suggests that the tool can validate previously recruited cases and is very fast at searching phenotypes; time for recruitment criteria checking was reduced from days to minutes. Validated on open intensive care EHR data, Medical Information Mart for Intensive Care III, the vital signs extracted by SemEHR can achieve around 97% accuracy. CONCLUSION: Results from the multiple case studies demonstrate SemEHR's efficiency: weeks or months of work can be done within hours or minutes in some cases. SemEHR provides a more comprehensive view of patients, bringing in more and unexpected insight compared to study-oriented bespoke IE systems. SemEHR is open source, available at https://github.com/CogStack/SemEHR

Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

Novel concepts in virally induced asthma

Viruses are the predominant infectious cause of asthma exacerbations in the developed world. In addition, recent evidence strongly suggests that viral infections may also have a causal role in the development of childhood asthma. In this article, we will briefly describe the general perception of how the link between infections and asthma has changed over the last century, and then focus on very recent developments that have provided new insights into the contribution of viruses to asthma pathogenesis. Highlighted areas include the contribution of severe early life viral infections to asthma inception, genetic determinants of severe viral infections in infancy, the differences in innate and adaptive immune system cytokine responses to viral infection between asthmatic and nonasthmatic subjects, and a potential vaccine strategy to prevent severe early life virally-induced illness