A Characterization of Extractable, Hydroxylated Fatty Acid Bearing Components in Legionella Pneumophila

Extraction of the lipids of Legionella pneumophila yields phases unlike those produced from other Gram-negative bacteria. A viscous interface forms between the aqueous (wash) and organic phases. More than half of the hydroxylated fatty acids were found distributed between the aqueous phase and the interfacial material, fractions in which such constituents have not been reported in other Gram-negative species. It was further observed that after the material from the aqueous/interfacial phase was dissolved in methanol or chloroform/methanol (2:1 (V/V)), the addition of acetone would create a white, flocculent precipitate. Analyses showed that the supernatant contained fatty acids that were nonhydroxylated and the precipitate contained both nonhydroxylated and hydroxylated fatty acids. The acetone precipitate could be further purified by column chromatography. Material was eluted from a silicic acid column with sequential additions of chloroform, acetone, and methanol. It was found that the methanol fraction contained the majority of the hydroxylated fatty acid containing material. An improved method for extracting LPS-like material from Legionella pneumophila is presented. This study suggests that LPS-like material can be obtained from L. pneumophila in higher yield (6.4% of total cell weight), of higher purity (as indicated by SDS-PAGE), and by a simpler method than those previously reported. SDS-PAGE profiles of purified (acetone precipitation and column chromatographic separation) LPS-like material extracted with chloroform/methanol (2:1 (V/V)) from L. pneumophila are identical to the previously reported profiles for G. pneumophila LPS. The chemical analyses of the LPS-like material can only account for approximately one-half the isolated material weight. This is suggestive of a moiety that is as of yet undetectable by the means employed to characterize the LPS

Functional changes in gut microbiota during hematopoietic stem cell transplantation for severe combined immunodeficiency

[Editorial letter

Induced CNS expression of CXCL1 augments neurologic disease in a murine model of multiple sclerosis via enhanced neutrophil recruitment.

Increasing evidence points to an important role for neutrophils in participating in the pathogenesis of the human demyelinating disease MS and the animal model EAE. Therefore, a better understanding of the signals controlling migration of neutrophils as well as evaluating the role of these cells in demyelination is important to define cellular components that contribute to disease in MS patients. In this study, we examined the functional role of the chemokine CXCL1 in contributing to neuroinflammation and demyelination in EAE. Using transgenic mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein-positive cells, we have shown that sustained CXCL1 expression within the CNS increased the severity of clinical and histologic disease that was independent of an increase in the frequency of encephalitogenic Th1 and Th17 cells. Rather, disease was associated with enhanced recruitment of CD11b+ Ly6G+ neutrophils into the spinal cord. Targeting neutrophils resulted in a reduction in demyelination arguing for a role for these cells in myelin damage. Collectively, these findings emphasize that CXCL1-mediated attraction of neutrophils into the CNS augments demyelination suggesting that this signaling pathway may offer new targets for therapeutic intervention

Precision Nutrition and the Microbiome, Part I: Current State of the Science

peer-reviewedThe gut microbiota is a highly complex community which evolves and adapts to its host over a lifetime. It has been described as a virtual organ owing to the myriad of functions it performs, including the production of bioactive metabolites, regulation of immunity, energy homeostasis and protection against pathogens. These activities are dependent on the quantity and quality of the microbiota alongside its metabolic potential, which are dictated by a number of factors, including diet and host genetics. In this regard, the gut microbiome is malleable and varies significantly from host to host. These two features render the gut microbiome a candidate ‘organ’ for the possibility of precision microbiomics—the use of the gut microbiome as a biomarker to predict responsiveness to specific dietary constituents to generate precision diets and interventions for optimal health. With this in mind, this two-part review investigates the current state of the science in terms of the influence of diet and specific dietary components on the gut microbiota and subsequent consequences for health status, along with opportunities to modulate the microbiota for improved health and the potential of the microbiome as a biomarker to predict responsiveness to dietary components. In particular, in Part I, we examine the development of the microbiota from birth and its role in health. We investigate the consequences of poor-quality diet in relation to infection and inflammation and discuss diet-derived microbial metabolites which negatively impact health. We look at the role of diet in shaping the microbiome and the influence of specific dietary components, namely protein, fat and carbohydrates, on gut microbiota composition

Categorification of persistent homology

We redevelop persistent homology (topological persistence) from a categorical point of view. The main objects of study are diagrams, indexed by the poset of real numbers, in some target category. The set of such diagrams has an interleaving distance, which we show generalizes the previously-studied bottleneck distance. To illustrate the utility of this approach, we greatly generalize previous stability results for persistence, extended persistence, and kernel, image and cokernel persistence. We give a natural construction of a category of interleavings of these diagrams, and show that if the target category is abelian, so is this category of interleavings.Comment: 27 pages, v3: minor changes, to appear in Discrete & Computational Geometr

CWRML: representing crop wild relative conservation and use data in XML

Background Crop wild relatives are wild species that are closely related to crops. They are valuable as potential gene donors for crop improvement and may help to ensure food security for the future. However, they are becoming increasingly threatened in the wild and are inadequately conserved, both in situ and ex situ. Information about the conservation status and utilisation potential of crop wild relatives is diverse and dispersed, and no single agreed standard exists for representing such information; yet, this information is vital to ensure these species are effectively conserved and utilised. The European Community-funded project, European Crop Wild Relative Diversity Assessment and Conservation Forum, determined the minimum information requirements for the conservation and utilisation of crop wild relatives and created the Crop Wild Relative Information System, incorporating an eXtensible Markup Language (XML) schema to aid data sharing and exchange. Results Crop Wild Relative Markup Language (CWRML) was developed to represent the data necessary for crop wild relative conservation and ensure that they can be effectively utilised for crop improvement. The schema partitions data into taxon-, site-, and population-specific elements, to allow for integration with other more general conservation biology schemata which may emerge as accepted standards in the future. These elements are composed of sub-elements, which are structured in order to facilitate the use of the schema in a variety of crop wild relative conservation and use contexts. Pre-existing standards for data representation in conservation biology were reviewed and incorporated into the schema as restrictions on element data contents, where appropriate. Conclusion CWRML provides a flexible data communication format for representing in situ and ex situ conservation status of individual taxa as well as their utilisation potential. The development of the schema highlights a number of instances where additional standards-development may be valuable, particularly with regard to the representation of population-specific data and utilisation potential. As crop wild relatives are intrinsically no different to other wild plant species there is potential for the inclusion of CWRML data elements in the emerging standards for representation of biodiversity data

Climate forcing of unprecedented intense-hurricane activity in the last 2000 years

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Earth's Future 3 (2015): 49–65, doi:10.1002/2014EF000274.How climate controls hurricane variability has critical implications for society is not well understood. In part, our understanding is hampered by the short and incomplete observational hurricane record. Here we present a synthesis of intense-hurricane activity from the western North Atlantic over the past two millennia, which is supported by a new, exceptionally well-resolved record from Salt Pond, Massachusetts (USA). At Salt Pond, three coarse grained event beds deposited in the historical interval are consistent with severe hurricanes in 1991 (Bob), 1675, and 1635 C.E., and provide modern analogs for 32 other prehistoric event beds. Two intervals of heightened frequency of event bed deposition between 1400 and 1675 C.E. (10 events) and 150 and 1150 C.E. (23 events), represent the local expression of coherent regional patterns in intense-hurricane–induced event beds. Our synthesis indicates that much of the western North Atlantic appears to have been active between 250 and 1150 C.E., with high levels of activity persisting in the Caribbean and Gulf of Mexico until 1400 C.E. This interval was one with relatively warm sea surface temperatures (SSTs) in the main development region (MDR). A shift in activity to the North American east coast occurred ca. 1400 C.E., with more frequent severe hurricane strikes recorded from The Bahamas to New England between 1400 and 1675 C.E. A warm SST anomaly along the western North Atlantic, rather than within the MDR, likely contributed to the later active interval being restricted to the east coast.Funding was provided by US National Science Foundation (awards 0903020 and 1356708), the Risk Prediction Initiative at the Bermuda Institute for Ocean Sciences (BIOS), US Department of Energy National Institute for Climate Change Research, National Oceanic and Atmospheric Administration (award NA11OAR431010), and the Dalio Explore Fund

A novel chemogenomics analysis of G protein-coupled receptors (GPCRs) and their ligands: a potential strategy for receptor de-orphanization.

BACKGROUND: G protein-coupled receptors (GPCRs) represent a family of well-characterized drug targets with significant therapeutic value. Phylogenetic classifications may help to understand the characteristics of individual GPCRs and their subtypes. Previous phylogenetic classifications were all based on the sequences of receptors, adding only minor information about the ligand binding properties of the receptors. In this work, we compare a sequence-based classification of receptors to a ligand-based classification of the same group of receptors, and evaluate the potential to use sequence relatedness as a predictor for ligand interactions thus aiding the quest for ligands of orphan receptors. RESULTS: We present a classification of GPCRs that is purely based on their ligands, complementing sequence-based phylogenetic classifications of these receptors. Targets were hierarchically classified into phylogenetic trees, for both sequence space and ligand (substructure) space. The overall organization of the sequence-based tree and substructure-based tree was similar; in particular, the adenosine receptors cluster together as well as most peptide receptor subtypes (e.g. opioid, somatostatin) and adrenoceptor subtypes. In ligand space, the prostanoid and cannabinoid receptors are more distant from the other targets, whereas the tachykinin receptors, the oxytocin receptor, and serotonin receptors are closer to the other targets, which is indicative for ligand promiscuity. In 93% of the receptors studied, de-orphanization of a simulated orphan receptor using the ligands of related receptors performed better than random (AUC > 0.5) and for 35% of receptors de-orphanization performance was good (AUC > 0.7). CONCLUSIONS: We constructed a phylogenetic classification of GPCRs that is solely based on the ligands of these receptors. The similarities and differences with traditional sequence-based classifications were investigated: our ligand-based classification uncovers relationships among GPCRs that are not apparent from the sequence-based classification. This will shed light on potential cross-reactivity of GPCR ligands and will aid the design of new ligands with the desired activity profiles. In addition, we linked the ligand-based classification with a ligand-focused sequence-based classification described in literature and proved the potential of this method for de-orphanization of GPCRs.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are