Publications

Insights into visual pigment adaptation and diversity from model ecological and evolutionary systems

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Hauser FE, Chang BS

Curr Opin Genet Dev. Published Nov 2, 2017.
https://doi.org/10.1016/j.gde.2017.09.005

PMID: 29102895

Abstract

Sensory systems provide valuable insight into the evolution of molecular mechanisms underlying organismal anatomy, physiology, and behaviour. Visual pigments, which mediate the first step in visual transduction, offer a unique window into the relationship between molecular variation and visual performance, and enhance our understanding of how ecology, life history, and physiology may shape genetic variation across a variety of organisms. Here we review recent work investigating vertebrate visual pigments from a number of perspectives. Opsin gene duplication, loss, differential expression, structural variation, and the physiological context in which they operate, have profoundly shaped the visual capabilities of vertebrates adapting to novel environments. We note the importance of conceptual frameworks in investigating visual pigment diversity in vertebrates, highlighting key examples including evolutionary transitions between different photic environments, major shifts in life history evolution and ecology, evolutionary innovations in visual system anatomy and physiology, as well as shifts in visually mediated behaviours and behavioural ecology. We emphasize the utility of studying visual pigment evolution in the context of these different perspectives, and demonstrate how the integrative approaches discussed in this review contribute to a better understanding of the underlying molecular processes mediating adaptation in sensory systems, and the contexts in which they occur.

Staphylococcus aureus interaction with Pseudomonas aeruginosa biofilm enhances tobramycin resistance

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Beaudoin T, Yau YCW, Stapleton PJ, Gong Y, Wang PW, Guttman DS, Waters V

NPJ Biofilms Microbiomes. Published Oct 19, 2017.
https://doi.org/DOI

PMID: 29062489

Abstract

Antimicrobial resistance is a significant threat to the treatment of infectious disease. Multiple mechanisms of resistance to different classes of antibiotics have been identified and well-studied. However, these mechanisms are studied with bacteria in isolation, whereas often, infections have a polymicrobial basis. Using a biofilm slide chamber model, we visualized the formation and development of clinical Pseudomonas aeruginosa biofilms in the presence of secreted Staphylococcus aureus exoproducts, two bacteria that commonly co-infect pediatric patients with cystic fibrosis. We showed that, over time, certain isolates of P. aeruginosa can form different biofilm architecture in the presence of S. aureus exoproducts. We further determined that this interaction was dependent on Psl produced by P. aeruginosa and staphylococcal protein A from S. aureus. Importantly, we identified a mechanism of antibiotic resistance to tobramycin that is dependent on the polymicrobial interactions between these two bacteria. This interaction occurred in isolates of P. aeruginosa recovered from children with cystic fibrosis who failed to clear P. aeruginosa following inhaled tobramycin treatment.

Exocyst, exosomes, and autophagy in the regulation of Brassicaceae pollen-stigma interactions

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Goring DR

J Exp Bot. Published Sep 27, 2017.
https://doi.org/10.1093/jxb/erx340

PMID: 29036428

Abstract

Brassicaceae pollen-stigma interactions have been extensively studied in Brassica and Arabidopsis species to identify cellular events triggered in the stigmatic papillae by pollen contact. Compatible pollinations are linked to the activation of basal cellular responses in the stigmatic papillae, which include calcium gradients, actin networks, and polarized secretion. The occurrence of these cellular events in stigmatic papillae coincides with the stages of pollen hydration and pollen tube entry into the stigmatic papillar cell wall. However, the form of the vesicle trafficking appears to differ between species, with vesicle-like structures detected in Arabidopsis species while exosomes were found to be secreted in Brassica species. Around the same timeframe, self-incompatible pollen recognition leads altered cellular responses in the stigmatic papillae to interfere with basal compatible pollen responses and disrupt regulated secretion, causing self-pollen rejection. Here, the literature on the changing cellular dynamics in the stigmatic papillae following pollination is reviewed and discussed in the context of other well-characterized examples of polarized secretion in plants.

Cesarean Section, Formula Feeding, and Infant Antibiotic Exposure: Separate and Combined Impacts on Gut Microbial Changes in Later Infancy

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Yasmin F, Tun HM, Konya TB, Guttman DS, Chari RS, Field CJ, Becker AB, Mandhane PJ, Turvey SE, Subbarao P, Sears MR; CHILD Study Investigators, Scott JA, Dinu I, Kozyrskyj AL

Front Pediatr. Published Sep 26, 2017.
https://doi.org/10.3389/fped.2017.00200

PMID: 29018787

Abstract

Established during infancy, our complex gut microbial community is shaped by medical interventions and societal preferences, such as cesarean section, formula feeding, and antibiotic use. We undertook this study to apply the significance analysis of microarrays (SAM) method to quantify changes in gut microbial composition during later infancy following the most common birth and postnatal exposures affecting infant gut microbial composition. Gut microbiota of 166 full-term infants in the Canadian Healthy Infant Longitudinal Development birth cohort were profiled using 16S high-throughput gene sequencing. Infants were placed into groups according to mutually exclusive combinations of birth mode (vaginal/cesarean birth), breastfeeding status (yes/no), and antibiotic use (yes/no) by 3 months of age. Based on repeated permutations of data and adjustment for the false discovery rate, the SAM statistic identified statistically significant changes in gut microbial abundance between 3 months and 1 year of age within each infant group. We observed well-known patterns of microbial phyla succession in later infancy (declining Proteobacteria; increasing Firmicutes and Bacteroidetes) following vaginal birth, breastfeeding, and no antibiotic exposure. Genus Lactobacillus, Roseburia, and Faecalibacterium species appeared in the top 10 increases to microbial abundance in these infants. Deviations from this pattern were evident among infants with other perinatal co-exposures; notably, the largest number of microbial species with unchanged abundance was seen in gut microbiota following early cessation of breastfeeding in infants. With and without antibiotic exposure, the absence of a breast milk diet by 3 months of age following vaginal birth yielded a higher proportion of unchanged abundance of Bacteroidaceae and Enterobacteriaceae in later infancy, and a higher ratio of unchanged Enterobacteriaceae to Alcaligenaceae microbiota. Gut microbiota of infants born vaginally and exclusively formula fed became less enriched with family Veillonellaceae and Clostridiaceae, showed unchanging levels of Ruminococcaceae, and exhibited a greater decline in the Rikenellaceae/Bacteroidaceae ratio compared to their breastfed, vaginally delivered counterparts. These changes were also evident in cesarean-delivered infants to a lesser extent. The clinical relevance of these trajectories of microbial change is that they culminate in taxon-specific abundances in the gut microbiota of later infancy, which we and others have observed to be associated with food sensitization.

Accelerated Evolution and Functional Divergence of the Dim Light Visual Pigment Accompanies Cichlid Colonization of Central America

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Hauser FE, Ilves KL, Schott RK, Castiglione GM, López-Fernández H, Chang BSW

Mol Biol Evol. Published Oct 1, 2017.
https://doi.org/10.1093/molbev/msx192

PMID: 28957507

Abstract

Cichlids encompass one of the most diverse groups of fishes in South and Central America, and show extensive variation in life history, morphology, and colouration. While studies of visual system evolution in cichlids have focussed largely on the African rift lake species flocks, Neotropical cichlids offer a unique opportunity to investigate visual system evolution at broader temporal and geographic scales. South American cichlid colonization of Central America has likely promoted accelerated rates of morphological evolution in Central American lineages as they encountered reduced competition, renewed ecological opportunity, and novel aquatic habitats. To investigate whether such transitions have influenced molecular evolution of vision in Central American cichlids, we sequenced the dim-light rhodopsin gene in 101 Neotropical cichlid species, spanning the diversity of the clade. We find strong evidence for increased rates of evolution in Central American cichlid rhodopsin relative to South American lineages, and identify several sites under positive selection in rhodopsin that likely contribute to adaptation to different photic environments. We expressed a Neotropical cichlid rhodopsin protein invitro for the first time, and found that while its spectral tuning properties were characteristic of typical vertebrate rhodopsin pigments, the rate of decay of its active signalling form was much slower, consistent with dim light adaptation in other vertebrate rhodopsins. Using site-directed mutagenesis combined with spectroscopic assays, we found that a key amino acid substitution present in some Central American cichlids accelerates the rate of decay of active rhodopsin, which may mediate adaptation to clear water habitats.

Impact of Immunosuppression on the Metagenomic Composition of the Intestinal Microbiome: a Systems Biology Approach to Post-Transplant Diabetes

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Bhat M, Pasini E, Copeland J, Angeli M, Husain S, Kumar D, Renner E, Teterina A, Allard J, Guttman DS, Humar A

Sci Rep. Published Aug 31, 2017.
https://doi.org/10.1038/s41598-017-10471-2

PMID: 28860611

Abstract

Solid organ transplantation (SOT) outcomes have continued to improve, although long-term use of immunosuppressants can lead to complications such as diabetes, compromising post-transplant outcomes. In this study, we have characterized the intestinal microbiome (IM) composition at the metagenomic level in the context of hyperglycemia induced by immunosuppressants. Sprague-Dawley rats were subjected to doses of tacrolimus and sirolimus that reliably induce hyperglycemia and an insulin-resistant state. Subsequent exposure to probiotics resulted in reversal of hyperglycemia. 16S rRNA and metagenomic sequencing of stool were done to identify the bacterial genes and pathways enriched in immunosuppression. Bacterial diversity was significantly decreased in sirolimus-treated rats, with 9 taxa significantly less present in both immunosuppression groups: Roseburia, Oscillospira, Mollicutes, Rothia, Micrococcaceae, Actinomycetales and Staphylococcus. Following probiotics, these changes were reversed to baseline. At the metagenomic level, the balance of metabolism was shifted towards the catabolic side with an increase of genes involved in sucrose degradation, similar to diabetes. Conversely, the control rats had greater abundance of anabolic processes and genes involved in starch degradation. Immunosuppression leads to a more catabolic microbial profile, which may influence development of diabetes after SOT. Modulation of the microbiome with probiotics may help in minimizing adverse long-term effects of immunosuppression.

A Practical Guide to Quantitative Interactor Screening with Next-Generation Sequencing (QIS-Seq)

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Gong Y, Desveaux D, Guttman DS, Lewis JD

Methods Mol Biol. Published Aug 2017.
https://doi.org/10.1007/978-1-4939-7027-8_1

PMID: 28849555

Abstract

Yeast two-hybrid screens are a powerful approach to identify protein-protein interactions; however, they are typically limited in the number of interactions identified, and lack quantitative values to ascribe confidence scores to the interactions that are obtained. We have developed a high-throughput, quantitative, yeast two-hybrid screening approach coupled with next-generation sequencing. This strategy allows the identification of interacting proteins that are preferentially associated with a bait of interest, and helps eliminate nonspecific interacting proteins. The method is high-throughput, allowing many more baits to be tested and many more candidate interacting proteins to be identified. Quantitative data allows the interactors to be ascribed confidence scores based on their enrichment with particular baits, and can identify both common and rare interacting proteins.

Draft Genome Sequences of 10 Environmental Pseudomonas aeruginosa Strains Isolated from Soils, Sediments, and Waters

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Shrestha SD, Guttman DS, Perron GG

Genome Announc. Published Aug 24, 2017.
https://doi.org/10.1128/genomeA.00804-17

PMID: 28839021

Abstract

Pseudomonas aeruginosa is an important opportunistic pathogen that has the ability to grow in a range of environmental niches. Here, we report the draft genome sequences of 10 environmental strains of the bacterium isolated from soils, sediments, and waters in various locations in North America and South Africa.

Expression profiles of miRNAs from bovine mammary glands in response to Streptococcus agalactiae-induced mastitis

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Pu J, Li R, Zhang C, Chen D, Liao X, Zhu Y, Geng X, Ji D, Mao Y, Gong Y, Yang Z

J Dairy Res. Published Aug 2017.
https://doi.org/10.1017/S0022029917000437

PMID: 28831974

Abstract

This study aimed to describe the expression profiles of microRNAs (miRNAs) from mammary gland tissues collected from dairy cows with Streptococcus agalactiae-induced mastitis and to identify differentially expressed miRNAs related to mastitis. The mammary glands of Chinese Holstein cows were challenged with Streptococcus agalactiae to induce mastitis. Small RNAs were isolated from the mammary tissues of the test and control groups and then sequenced using the Solexa sequencing technology to construct two small RNA libraries. Potential target genes of these differentially expressed miRNAs were predicted using the RNAhybrid software, and KEGG pathways associated with these genes were analysed. A total of 18 555 913 and 20 847 000 effective reads were obtained from the test and control groups, respectively. In total, 373 known and 399 novel miRNAs were detected in the test group, and 358 known and 232 novel miRNAs were uncovered in the control group. A total of 35 differentially expressed miRNAs were identified in the test group compared to the control group, including 10 up-regulated miRNAs and 25 down-regulated miRNAs. Of these miRNAs, miR-223 exhibited the highest degree of up-regulation with an approximately 3-fold increase in expression, whereas miR-26a exhibited the most decreased expression level (more than 2-fold). The RNAhybrid software predicted 18 801 genes as potential targets of these 35 miRNAs. Furthermore, several immune response and signal transduction pathways, including the RIG-I-like receptor signalling pathway, cytosolic DNA sensing pathway and Notch signal pathway, were enriched in these predicted targets. In summary, this study provided experimental evidence for the mechanism underlying the regulation of bovine mastitis by miRNAs and showed that miRNAs might be involved in signal pathways during S. agalactiae-induced mastitis.

ePlant: Visualizing and Exploring Multiple Levels of Data for Hypothesis Generation in Plant Biology

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Waese J, Fan J, Pasha A, Yu H, Fucile G, Shi R, Cumming M, Kelley LA, Sternberg MJ, Krishnakumar V, Ferlanti E, Miller J, Town C, Stuerzlinger W, Provart NJ

Plant Cell. Published Aug 2017.
https://doi.org/10.1105/tpc.17.00073

PMID: 28808136

Abstract

A big challenge in current systems biology research arises when different types of data must be accessed from separate sources and visualized using separate tools. The high cognitive load required to navigate such a workflow is detrimental to hypothesis generation. Accordingly, there is a need for a robust research platform that incorporates all data and provides integrated search, analysis, and visualization features through a single portal. Here, we present ePlant (http://bar.utoronto.ca/eplant), a visual analytic tool for exploring multiple levels of Arabidopsis thaliana data through a zoomable user interface. ePlant connects to several publicly available web services to download genome, proteome, interactome, transcriptome, and 3D molecular structure data for one or more genes or gene products of interest. Data are displayed with a set of visualization tools that are presented using a conceptual hierarchy from big to small, and many of the tools combine information from more than one data type. We describe the development of ePlant in this article and present several examples illustrating its integrative features for hypothesis generation. We also describe the process of deploying ePlant as an “app” on Araport. Building on readily available web services, the code for ePlant is freely available for any other biological species research.