Category: Publications

Regulation of obesity-related insulin resistance with gut anti-inflammatory agents

Posted on by biota in Publications

Luck H, Tsai S, Chung J, Clemente-Casares X, Ghazarian M, Revelo XS, Lei H, Luk CT, Shi SY, Surendra A, Copeland JK, Ahn J, Prescott D, Rasmussen BA, Chng MH, Engleman EG, Girardin SE, Lam TK, Croitoru K, Dunn S, Philpott DJ, Guttman DS, Woo M, Winer S, Winer DA

Cell Metab. 2015 Apr;21(4):527-42

PMID: 25863246

Abstract

Obesity has reached epidemic proportions, but little is known about its influence on the intestinal immune system. Here we show that the gut immune system is altered during high-fat diet (HFD) feeding and is a functional regulator of obesity-related insulin resistance (IR) that can be exploited therapeutically. Obesity induces a chronic phenotypic pro-inflammatory shift in bowel lamina propria immune cell populations. Reduction of the gut immune system, using beta7 integrin-deficient mice (Beta7(null)), decreases HFD-induced IR. Treatment of wild-type HFD C57BL/6 mice with the local gut anti-inflammatory, 5-aminosalicyclic acid (5-ASA), reverses bowel inflammation and improves metabolic parameters. These beneficial effects are dependent on adaptive and gut immunity and are associated with reduced gut permeability and endotoxemia, decreased visceral adipose tissue inflammation, and improved antigen-specific tolerance to luminal antigens. Thus, the mucosal immune system affects multiple pathways associated with systemic IR and represents a novel therapeutic target in this disease.

Transcriptome microRNA profiling of bovine mammary glands infected with Staphylococcus aureus

Posted on by biota in Publications

Li R, Zhang CL, Liao XX, Chen D, Wang WQ, Zhu YH, Geng XH, Ji DJ, Mao YJ, Gong YC, Yang ZP

Int J Mol Sci 2015;16(3):4997-5013

PMID: 25749476

Abstract

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows.

Crossroads of stress responses, development and flowering regulation–the multiple roles of Cyclic Nucleotide Gated Ion Channel 2

Posted on by biota in Publications

Fortuna A, Lee J, Ung H, Chin K, Moeder W, Yoshioka K

Plant Signal Behav 2015;10(3):e989758

PMID: 25719935

Abstract

The Arabidopsis autoimmune mutant, defense-no death 1 (dnd1) is a null mutant of CYCLIC NUCLEOTIDE-GATED ION CHANNEL2 (AtCNGC2). dnd1 exhibits constitutive pathogen resistance responses including higher levels of endogenous salicylic acid (SA), which is an important signaling molecule for pathogen defense responses. Recently we have reported that dnd1 exhibits a significantly delayed flowering phenotype, indicating the involvement of AtCNGC2 in flowering transition. However, since SA has been known to influence flowering timing as a positive regulator, the delayed flowering phenotype in dnd1 was unexpected. In this study, we have asked whether SA is involved in the dnd1-mediated delayed flowering phenotype. In addition, in order to gain insight into the involvement of SA and CNGCs in flowering transition, we analyzed the flowering transition of cpr22, another CNGC mutant with a similar autoimmune phenotype as dnd1 (including high SA accumulation), and null mutants of several other CNGCs. Our data suggest that dnd1 does not require SA or SA signaling for its delayed flowering phenotype, while SA was responsible for the early flowering phenotype of cpr22. None of the other CNGC mutants besides AtCNGC4 (1) displayed an alteration in flowering transition. This indicates that AtCNGC2 and AtCNGC4 have a unique role controlling flowering timing and this function is independent from its role in pathogen defense.

Reduced plant competition among kin can be explained by Jensen’s inequality

Posted on by biota in Publications

Simonsen AK, Chow T, Stinchcombe JR

Ecol Evol 2014 Dec;4(23):4454-66

PMID: 25512842

Abstract

Plants often compete with closely related individuals due to limited dispersal, leading to two commonly invoked predictions on competitive outcomes. Kin selection, from evolutionary theory, predicts that competition between relatives will likely be weaker. The niche partitioning hypothesis, from ecological theory, predicts that competition between close relatives will likely be stronger. We tested for evidence consistent with either of these predictions by growing an annual legume in kin and nonkin groups in the greenhouse. We grew plant groups in treatments of symbiotic nitrogen fixing bacteria differing in strain identity and composition to determine if differences in the microbial environment can facilitate or obscure plant competition patterns consistent with kin selection or niche partitioning. Nonkin groups had lower fitness than expected, based on fitness estimates of the same genotypes grown among kin. Higher fitness among kin groups was observed in mixtures of N-fixing bacteria strains compared to single inoculations of bacteria strains present in the soil, which increased fitness differences between kin and nonkin groups. Lower fitness in nonkin groups was likely caused by increased competitive asymmetry in nonkin groups due to genetic differences in plant size combined with saturating relationships with plant size and fitness- i.e. Jensen’s inequality. Our study suggests that microbial soil symbionts alter competitive dynamics among kin and nonkin. Our study also suggests that kin groups can have higher fitness, as predicted by kin selection theory, through a commonly heritable trait (plant size), without requiring kin recognition mechanisms.

SWS2 visual pigment evolution as a test of historically contingent patterns of plumage color evolution in warblers

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Bloch NI, Morrow JM, Chang BS, Price TD

Evolution 2015 Feb;69(2):341-56

PMID: 25496318

Abstract

Distantly related clades that occupy similar environments may differ due to the lasting imprint of their ancestors-historical contingency. The New World warblers (Parulidae) and Old World warblers (Phylloscopidae) are ecologically similar clades that differ strikingly in plumage coloration. We studied genetic and functional evolution of the short-wavelength-sensitive visual pigments (SWS2 and SWS1) to ask if altered color perception could contribute to the plumage color differences between clades. We show SWS2 is short-wavelength shifted in birds that occupy open environments, such as finches, compared to those in closed environments, including warblers. Phylogenetic reconstructions indicate New World warblers were derived from a finch-like form that colonized from the Old World 15-20 Ma. During this process, the SWS2 gene accumulated six substitutions in branches leading to New World warblers, inviting the hypothesis that passage through a finch-like ancestor resulted in SWS2 evolution. In fact, we show spectral tuning remained similar across warblers as well as the finch ancestor. Results reject the hypothesis of historical contingency based on opsin spectral tuning, but point to evolution of other aspects of visual pigment function. Using the approach outlined here, historical contingency becomes a generally testable theory in systems where genotype and phenotype can be connected.

Arabidopsis triphosphate tunnel metalloenzyme2 is a negative regulator of the salicylic acid-mediated feedback amplification loop for defense responses

Posted on by biota in Publications

Ung H, Moeder W, Yoshioka K

Plant Physiol. 2014 Oct;166(2):1009-21

PMID: 25185123

Abstract

The triphosphate tunnel metalloenzyme (TTM) superfamily represents a group of enzymes that is characterized by their ability to hydrolyze a range of tripolyphosphate substrates. Arabidopsis (Arabidopsis thaliana) encodes three TTM genes, AtTTM1, AtTTM2, and AtTTM3. Although AtTTM3 has previously been reported to have tripolyphosphatase activity, recombinantly expressed AtTTM2 unexpectedly exhibited pyrophosphatase activity. AtTTM2 knockout mutant plants exhibit an enhanced hypersensitive response, elevated pathogen resistance against both virulent and avirulent pathogens, and elevated accumulation of salicylic acid (SA) upon infection. In addition, stronger systemic acquired resistance compared with wild-type plants was observed. These enhanced defense responses are dependent on SA, PHYTOALEXIN-DEFICIENT4, and NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1. Despite their enhanced pathogen resistance, ttm2 plants did not display constitutively active defense responses, suggesting that AtTTM2 is not a conventional negative regulator but a negative regulator of the amplification of defense responses. The transcriptional suppression of AtTTM2 by pathogen infection or treatment with SA or the systemic acquired resistance activator benzothiadiazole further supports this notion. Such transcriptional regulation is conserved among TTM2 orthologs in the crop plants soybean (Glycine max) and canola (Brassica napus), suggesting that TTM2 is involved in immunity in a wide variety of plant species. This indicates the possible usage of TTM2 knockout mutants for agricultural applications to generate pathogen-resistant crop plants.

Distinct subclades of Aux/IAA genes are direct targets of ARF5/MP transcriptional regulation

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Krogan NT, Yin X, Ckurshumova W, Berleth T

New Phytol. 2014 Nov;204(3):474-83

PMID: 25145395

Abstract

The regulatory interactions between AUXIN RESPONSE FACTORS (ARFs) and Aux/IAA repressors play a central role in auxin signal transduction. Yet, the systems properties of this regulatory network are not well established. We generated a steroid-inducible ARF5/MONOPTEROS (MP) transgenic background to survey the involvement of this factor in the transcriptional regulation of the entire Aux/IAA family in Arabidopsis thaliana. Target genes of ARF5/MP identified by this approach were confirmed by chromatin immunoprecipitation, in vitro gel retardation assays and gene expression analyses. Our study shows that ARF5/MP is indispensable for the correct regulation of nearly one-half of all Aux/IAA genes, and that these targets coincide with distinct subclades. Further, genetic analyses demonstrate that the protein products of multiple Aux/IAA targets negatively feed back onto ARF5/MP activity. This work indicates that ARF5/MP broadly influences the expression of the Aux/IAA gene family, and suggests that such regulation involves the activation of specific subsets of redundantly functioning factors. These groups of factors may then act together to control various processes within the plant through negative feedback on ARF5. Similar detailed analyses of other Aux/IAA-ARF regulatory modules will be required to fully understand how auxin signal transduction influences virtually every aspect of plant growth and development.

Dispersal analysis of three Peltigera species based on landscape genetics data

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Anstett DN, O’Brien H, Larsen EW, McMullin RT, Fortin MJ

Mycology 2013 Dec;4(4):187-195

PMID: 24605248

Abstract

Lichens can either disperse sexually through fungal spores or asexually through vegetative propagules and fragmentation. Understanding how genetic variation in lichens is distributed across a landscape can be useful to infer dispersal and establishment events in space and time as well as the conditions needed for this establishment. Most studies have sampled lichens across large spatial distances on the order of hundreds of kilometers, while here we sequence the internal transcribed spacer (ITS) for 113 samples of three Peltigera species sampling at a variety of small spatial scales. The maximum distance between sampled lichens was 3.7 km and minimum distance was approximately 20 cm. We find significant amounts of genetic diversity across all three species. For P. praetextata, two out of the three most common ITS genotypes exhibit spatial autocorrelation supporting short-range dispersal. Using rarefaction we estimate that all ITS genotypes in our sampling area have been found for P. praetextata and P. evansiana, but not P. canina. Comparing our results with other ITS data in the literature provides evidence for global dispersal for at least one sequence followed by the evolution of endemic haplotypes with wide dispersal and rare haplotypes with more local dispersal.

Divergent positive selection in rhodopsin from lake and riverine cichlid fishes

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Schott RK, Refvik SP, Hauser FE, López-Fernández H, Chang BS

Mol. Biol. Evol. 2014 May;31(5):1149-65

PMID: 24509690

Abstract

Studies of cichlid evolution have highlighted the importance of visual pigment genes in the spectacular radiation of the African rift lake cichlids. Recent work, however, has also provided strong evidence for adaptive diversification of riverine cichlids in the Neotropics, which inhabit environments of markedly different spectral properties from the African rift lakes. These ecological and/or biogeographic differences may have imposed divergent selective pressures on the evolution of the cichlid visual system. To test these hypotheses, we investigated the molecular evolution of the dim-light visual pigment, rhodopsin. We sequenced rhodopsin from Neotropical and African riverine cichlids and combined these data with published sequences from African cichlids. We found significant evidence for positive selection using random sites codon models in all cichlid groups, with the highest levels in African lake cichlids. Tests using branch-site and clade models that partitioned the data along ecological (lake, river) and/or biogeographic (African, Neotropical) boundaries found significant evidence of divergent selective pressures among cichlid groups. However, statistical comparisons among these models suggest that ecological, rather than biogeographic, factors may be responsible for divergent selective pressures that have shaped the evolution of the visual system in cichlids. We found that branch-site models did not perform as well as clade models for our data set, in which there was evidence for positive selection in the background. One of our most intriguing results is that the amino acid sites found to be under positive selection in Neotropical and African lake cichlids were largely nonoverlapping, despite falling into the same three functional categories: spectral tuning, retinal uptake/release, and rhodopsin dimerization. Taken together, these results would imply divergent selection across cichlid clades, but targeting similar functions. This study highlights the importance of molecular investigations of ecologically important groups and the flexibility of clade models in explicitly testing ecological hypotheses.

Seasonal community succession of the phyllosphere microbiome

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Copeland JK, Yuan L, Layeghifard M, Wang PW, Guttman DS

Mol. Plant Microbe Interact. 2015 Mar;28(3):274-85

PMID: 25679538

Abstract

The leaf microbiome is influenced by both biotic and abiotic factors. Currently, we know little about the relative importance of these factors in determining microbiota composition and dynamics. To explore this issue, we collected weekly leaf samples over a 98-day growing season from multiple cultivars of common bean, soybean, and canola planted at three locations in Ontario, Canada, and performed Illumina-based microbiome analysis. We find that the leaf microbiota at the beginning of the season is very strongly influenced by the soil microbiota but, as the season progresses, it differentiates, becomes significantly less diverse, and transitions to having a greater proportion of leaf-specific taxa that are shared among all samples. A phylogenetic investigation of communities by reconstruction of unobserved states imputation of microbiome function inferred from the taxonomic data found significant differences between the soil and leaf microbiome, with a significant enrichment of motility gene categories in the former and metabolic gene categories in the latter. A network co-occurrence analysis identified two highly connected clusters as well as subclusters of putative pathogens and growth-promoting bacteria. These data reveal some of the complex ecological dynamics that occur in microbial communities over the course of a growing season and highlight the importance of community succession.