An R package to analyse LC/MS metabolomic data: MAIT (Metabolite Automatic Identification Toolkit)

Current tools for liquid chromatography and mass spectrometry for metabolomic data cover a limited number of processing steps, whereas online tools are hard to use in a programmable fashion. This article introduces the Metabolite Automatic Identification Toolkit (MAIT) package, which makes it possible for users to perform metabolomic end-to-end liquid chromatography and mass spectrometry data analysis. MAIT is focused on improving the peak annotation stage and provides essential tools to validate statistical analysis results. MAIT generates output files with the statistical results, peak annotation and metabolite identification. AVAILABILITY AND IMPLEMENTATION: http://b2slab.upc.edu/software-and-downloads/metabolite-automatic-identification-toolkit/

Metabolomics methods for the synthetic biology of secondary metabolism

Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that have never been observed before. The stimulation or “awakening” of this cryptic microbial secondary metabolism has naturally attracted the attention of synthetic microbiologists, who exploit recent advances in DNA sequencing and synthesis to achieve unprecedented control over metabolic pathways. One of the indispensable tools in the synthetic biology toolbox is metabolomics, the global quantification of small biomolecules. This review illustrates the pivotal role of metabolomics for the synthetic microbiology of secondary metabolism, including its crucial role in novel compound discovery in microbes, the examination of side products of engineered metabolic pathways, as well as the identification of major bottlenecks for the overproduction of compounds of interest, especially in combination with metabolic modeling. We conclude by highlighting remaining challenges and recent technological advances that will drive metabolomics towards fulfilling its potential as a cornerstone technology of synthetic microbiology

The Effect of Transposable Element Insertions on Gene Expression Evolution in Rodents

Background:Many genomes contain a substantial number of transposable elements (TEs), a few of which are known to be involved in regulating gene expression. However, recent observations suggest that TEs may have played a very important role in the evolution of gene expression because many conserved non-genic sequences, some of which are know to be involved in gene regulation, resemble TEs. Results:Here we investigate whether new TE insertions affect gene expression profiles by testing whether gene expression divergence between mouse and rat is correlated to the numbers of new transposable elements inserted near genes. We show that expression divergence is significantly correlated to the number of new LTR and SINE elements, but not to the numbers of LINEs. We also show that expression divergence is not significantly correlated to the numbers of ancestral TEs in most cases, which suggests that the correlations between expression divergence and the numbers of new TEs are causal in nature. We quantify the effect and estimate that TE insertion has accounted for ~20% (95% confidence interval: 12% to 26%) of all expression profile divergence in rodents. Conclusions:We conclude that TE insertions may have had a major impact on the evolution of gene expression levels in rodents

Leveraging Herbaria Specimens: A New 3D Imaging Protocol and Analyses of Diversity of West Virginia Rosids

Herbaria are repositories of plant natural history, whose data can provide insights into the life histories of plant taxa over space and time. Recent initiatives to digitize herbarium data have made studies over broad geographic and taxonomic extents possible, with the ability of scientists to access data from large databases of herbaria. Most of the digitization initiatives have focused on flat 2D herbaria sheets, but herbaria also include 3D collections, such as fungi, mosses, lichens, and dry fruits. In Chapter 1 we propose an easy and cost-effective workflow that uses free photogrammetry software to produce 3D images of 3D herbaria specimens. We tested four free to use photogrammetry software and created 3D images of five types of 3D specimens: a fungus, a moss, a lichen, a pinecone, and a compound fruit. With our workflow using equipment already present in most herbarium digitization stations, we produced 3D specimens in less than an hour. The software 3DF Zephyr Free gave the best results across each specimen type. Our workflow has provided an easy and low-cost method of producing 3D images that can be used to digitize 3D specimens in a similar manner to 2D herbaria sheets. In Chapter 2 we used herbaria data to analyze the spatial patterns of diversity of a major clade of plants, the Rosids, that contain most hardwood trees in West Virginia, and are the dominant plant species in the state. We used phylogenetic diversity to assess the diversity of this clade across the Level IV Ecoregions of West Virginia. Phylogenetic diversity (PD) is a metric that incorporates the evolutionary history of an area of interest. Ecoregions are defined by the Environmental Protection Agency (EPA) as areas of similar habitat, climate, and species composition. Our results indicated high PD in the eastern portion of the state in the Monongahela National Forest and low PD in the southern portion of the state in the Dissected Appalachian Plateau ecoregion. Analyses such as ours are important for informing conservation priorities, as they identify specific areas that are more biodiverse

The Olfactory Nervous System Of Terrestrial And Aquatic Vertebrates

Animals in their natural milieu are surrounded by odors. These odors are rich source of information, and are perceived by sophisticated olfactory systems, that have evolved over time. The sense of smell helps species to localize prey, evade predators, explore food and recognize viable mates. In humans, memoirs, thoughts, emotions, and associations are more readily reached through the sense of smell than through any other channel. This suggests that olfactory processing is imperative and may differ fundamentally from processing in other sensory modalities. The molecular age in olfaction initiated in 1991 with the significant discovery of a large, multigene family of olfactory receptors in rat by Linda Buck and Richard Axel (Buck and Axel, 1991). The first cloned olfactory receptors consisted of a diverse repertoire of G-protein coupled receptors (GPCRs) with seven-trans membrane topology, and they were sparsely expressed in the olfactory epithelium. This Nobel Prize worthy pioneering discovery, together with availability of modern techniques and numerous completely sequenced genomes opened the way to characterize the gene families of olfactory receptors through exhaustive computational data mining in different species genome as well as by in vitro biology. In this review, I will explain about the two main model organism of olfactory perceptions, zebrafish and mouse

Snake Cathelicidin from Bungarus fasciatus Is a Potent Peptide Antibiotics

Background: Cathelicidins are a family of antimicrobial peptides acting as multifunctional effector molecules of innate immunity, which are firstly found in mammalians. Recently, several cathelicidins have also been found from chickens and fishes. No cathelicidins from other non-mammalian vertebrates have been reported. Principal Findings: In this work, a cathelicidin-like antimicrobial peptide named cathelicidin-BF has been purified from the snake venoms of Bungarus fasciatus and its cDNA sequence was cloned from the cDNA library, which confirm the presence of cathelicidin in reptiles. As other cathelicidins, the precursor of cathelicidin-BF has cathelin-like domain at the N terminus and carry the mature cathelicidin-BF at the C terminus, but it has an atypical acidic fragment insertion between the cathelin-like domain and the C-terminus. The acidic fragment is similar to acidic domains of amphibian antimicrobial precursors. Phylogenetic analysis revealed that the snake cathelicidin had the nearest evolution relationship with platypus cathelicidin. The secondary structure of cathelicidin-BF investigated by CD and NMR spectroscopy in the presence of the helicogenic solvent TFE is an amphipathic α-helical conformation as many other cathelicidins. The antimicrobial activities of cathelicidin BF against forty strains of microorganisms were tested. Cathelicidin-BF efficiently killed bacteria and some fungal species including clinically isolated drug-resistance microorganisms. It was especially active against Gram-negative bacteria. Furthermore, it could exert antimicrobial activity against some saprophytic fungus. No hemolytic and cytotoxic activity was observed at the dose of up to 400 µg/ml. Cathelicidin-BF could exist stably in the mice plasma for at least 2.5 hours. Conclusion: Discovery of snake cathelicidin with atypical structural and functional characterization offers new insights on the evolution of cathelicidins. Potent, broad spectrum, salt-independent antimicrobial activities make cathelicidin-BF an excellent candidate for clinical or agricultural antibiotics

Plasma Biomarkers for Monitoring Brain Pathophysiology in FMR1 Premutation Carriers.

Premutation carriers have a 55-200 CGG expansion in the fragile X mental retardation 1 (FMR1) gene. Currently, 1.5 million individuals are affected in the United States, and carriers are at risk of developing the late-onset neurodegenerative disorder Fragile X-associated tremor ataxia syndrome (FXTAS). Limited efforts have been made to develop new methods for improved early patient monitoring, treatment response, and disease progression. To this end, plasma metabolomic phenotyping was obtained for 23 premutation carriers and 16 age- and sex-matched controls. Three biomarkers, phenylethylamine normalized by either aconitate or isocitrate and oleamide normalized by isocitrate, exhibited excellent model performance. The lower phenylethylamine and oleamide plasma levels in carriers may indicate, respectively, incipient nigrostriatal degeneration and higher incidence of substance abuse, anxiety and sleep disturbances. Higher levels of citrate, isocitrate, aconitate, and lactate may reflect deficits in both bioenergetics and neurotransmitter metabolism (Glu, GABA). This study lays important groundwork by defining the potential utility of plasma metabolic profiling to monitor brain pathophysiology in carriers before and during the progression of FXTAS, treatment efficacy and evaluation of side effects

Evolutionary constraints on the complexity of genetic regulatory networks allow predictions of the total number of genetic interactions

Genetic regulatory networks (GRNs) have been widely studied, yet there is a lack of understanding with regards to the final size and properties of these networks, mainly due to no network currently being complete. In this study, we analyzed the distribution of GRN structural properties across a large set of distinct prokaryotic organisms and found a set of constrained characteristics such as network density and number of regulators. Our results allowed us to estimate the number of interactions that complete networks would have, a valuable insight that could aid in the daunting task of network curation, prediction, and validation. Using state-of-the-art statistical approaches, we also provided new evidence to settle a previously stated controversy that raised the possibility of complete biological networks being random and therefore attributing the observed scale-free properties to an artifact emerging from the sampling process during network discovery. Furthermore, we identified a set of properties that enabled us to assess the consistency of the connectivity distribution for various GRNs against different alternative statistical distributions. Our results favor the hypothesis that highly connected nodes (hubs) are not a consequence of network incompleteness. Finally, an interaction coverage computed for the GRNs as a proxy for completeness revealed that high-throughput based reconstructions of GRNs could yield biased networks with a low average clustering coefficient, showing that classical targeted discovery of interactions is still needed.Comment: 28 pages, 5 figures, 12 pages supplementary informatio