Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Background: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from reinfection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157: H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. Results: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed. Conclusions: Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157: H7 (Stx(-)) due to an upregulation of immune suppressive effects (7/12 genes) or a downregulation of immunostimulatory effects (69/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function

Endogenous IL-33 and Its Autoamplification of IL-33/ST2 Pathway Play an Important Role in Asthma.

IL-33 and its receptor ST2 are contributing factors to airway inflammation and asthma exacerbation. The IL-33/ST2 signaling pathway is involved in both the onset and the acute exacerbations of asthma. In this study, we address the role of endogenous IL-33 and its autoamplification of the IL-33/ST2 pathway in Ag-dependent and Ag-independent asthma-like models. Wild-type, IL-33 knockout, ST2 knockout mice were either intratracheally administrated with 500 ng of rIL-33 per day for four consecutive days or were sensitized and challenged with OVA over 21 d. In wild-type mice, IL-33 or OVA induced similar airway hyperresponsiveness and eosinophilic airway inflammation. IL-33 induced its own mRNA and ST2L mRNA expression in the lung. IL-33 autoamplified itself and ST2 protein expression in airway epithelial cells. OVA also induced IL-33 and ST2 protein expression. In IL-33 knockout mice, the IL-33- and OVA-induced airway hyperresponsiveness and eosinophilic airway inflammation were both significantly attenuated, whereas IL-33-induced ST2L mRNA expression was preserved, although no autoamplification of IL-33/ST2 pathway was observed. In ST2 knockout mice, IL-33 and OVA induced airway hyperresponsiveness and eosinophilic airway inflammation were both completely diminished, and no IL-33/ST2 autoamplification was observed. These results suggest that endogenous IL-33 and its autoamplification of IL-33/ST2 pathway play an important role in the induction of asthma-like phenotype. Thus an intact IL-33/ST2 pathway is necessary for both Ag-dependent and Ag-independent asthma-like mouse models

Evidence that natural selection maintains genetic variation for sleep in Drosophila melanogaster.

BackgroundDrosophila melanogaster often shows correlations between latitude and phenotypic or genetic variation on different continents, which suggests local adaptation with respect to a heterogeneous environment. Previous phenotypic analyses of latitudinal clines have investigated mainly physiological, morphological, or life-history traits. Here, we studied latitudinal variation in sleep in D. melanogaster populations from North and Central America. In parallel, we used RNA-seq to identify interpopulation gene expression differences.ResultsWe found that in D. melanogaster the average nighttime sleep bout duration exhibits a latitudinal cline such that sleep bouts of equatorial populations are roughly twice as long as those of temperate populations. Interestingly, this pattern of latitudinal variation is not observed for any daytime measure of activity or sleep. We also found evidence for geographic variation for sunrise anticipation. Our RNA-seq experiment carried out on heads from a low and high latitude population identified a large number of gene expression differences, most of which were time dependent. Differentially expressed genes were enriched in circadian regulated genes and enriched in genes potentially under spatially varying selection.ConclusionOur results are consistent with a mechanistic and selective decoupling of nighttime and daytime activity. Furthermore, the present study suggests that natural selection plays a major role in generating transcriptomic variation associated with circadian behaviors. Finally, we identified genomic variants plausibly causally associated with the observed behavioral and transcriptomic variation

Profiling common types of research data and methods published by organic synthesis chemists at the University of Michigan

Objectives: The goal of this research was to create a landscape of organic synthetic chemistry data by manually analyzing a small but representative group of publications. Through this analysis, we hope to gain a better understanding of the various kinds of data and method entities and any associated attributes reported in the literature to inform upcoming metadata standards in this field. Methods: Publications authored by principal investigators (PIs) in the University of Michigan’s chemistry department that self-identify organic chemistry as their research area were collected. Only publications within the scope of organic synthetic chemistry published between 2012-2013 were included for analysis. Publications (including any supplementary information) were carefully examined and data and method information was recorded in the relational database. We identified specific data and method entities and any corresponding attributes, such as metadata and provenance. We compared the published names of the data and method types to the Chemical Methods Ontology (published by the Royal Society of Chemistry) to determine if they correspond. We then created profiles about each data and method type as well as their relationships. Results: Analysis of these publications generated 969 total pieces of data information, 111 different data types, 1308 total pieces of method information and 53 different method types.http://deepblue.lib.umich.edu/bitstream/2027.42/111832/1/DTP_SLA2015Poster_Ye_Joanna_20150610 copy.pd

The Catalytic and Non-catalytic Functions of the Brahma Chromatin-Remodeling Protein Collaborate to Fine-Tune Circadian Transcription in Drosophila.

Daily rhythms in gene expression play a critical role in the progression of circadian clocks, and are under regulation by transcription factor binding, histone modifications, RNA polymerase II (RNAPII) recruitment and elongation, and post-transcriptional mechanisms. Although previous studies have shown that clock-controlled genes exhibit rhythmic chromatin modifications, less is known about the functions performed by chromatin remodelers in animal clockwork. Here we have identified the Brahma (Brm) complex as a regulator of the Drosophila clock. In Drosophila, CLOCK (CLK) is the master transcriptional activator driving cyclical gene expression by participating in an auto-inhibitory feedback loop that involves stimulating the expression of the main negative regulators, period (per) and timeless (tim). BRM functions catalytically to increase nucleosome density at the promoters of per and tim, creating an overall restrictive chromatin landscape to limit transcriptional output during the active phase of cycling gene expression. In addition, the non-catalytic function of BRM regulates the level and binding of CLK to target promoters and maintains transient RNAPII stalling at the per promoter, likely by recruiting repressive and pausing factors. By disentangling its catalytic versus non-catalytic functions at the promoters of CLK target genes, we uncovered a multi-leveled mechanism in which BRM fine-tunes circadian transcription

Dynamics of Utah\u27s Agricultural Landscapes in Response to Urbanization: A Comparison Between Irrigated and Non-Irrigated Agricultural Lands

In the literature on how urbanization affects agricultural landscapes, little attention has been focused on differentiating and comparing the changes in irrigated agricultural landscapes to non-irrigated agricultural landscapes. Additionally, there have been few applications of landscape metrics for understanding agricultural landscape changes. The objectives of this study were to:(1) analyze and compare the changes of both irrigated and non-irrigated agricultural lands in a rapidly growing region; (2) identify the spatial patterns and hotspots of these changes; and,(3) examine the spatial relationships between changes in agricultural landscapes and urban development. We adopted landscape metrics and gradient analysis to assess where and how agricultural landscape changes occurred in northern Utah over the past 30 years. A revised urban gradient was also developed to detect the changes of agricultural landscapes in relation to new urban development. We found that irrigated agricultural lands were more affected by urban development than non-irrigated agricultural lands, with evidence of more patches, more irregular patch shapes, and less connectivity among patches. This study contributes not only to the existing literature on the dynamics of both irrigated and non-irrigated agricultural lands in relation to urban development, but also helps fill the gap of scant applications of landscape metrics and urban gradient analysis in agricultural areas. Most importantly, such a comprehensive examination of Utah\u27s agricultural landscapes will serve as part of the scientific foundation for informing land use policy in the region, as well as provide lessons for other places that are facing similar agricultural land conversion challenges

Chirality and Protein Folding

There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the RMSD distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wrong sense of chirality. We propose that a better condition of folding should augment the simple criteria with the requirement that most of the local values of the chirality should be nearly native. The kinetic discrepancy between the simple and compound criteria can be substantially reduced in the Go-like models by providing the Hamiltonian with a term which favors native values of the local chirality. We study the effects of this term as a function of its amplitude and compare it to other models such as with the side groups and with the angle-dependent potentials.Comment: To be published in a special issue of J. Phys.: Cond. Mat. (Bedlewo Workshop

The first symbiotic stars from the LAMOST survey

Symbiotic stars are interacting binary systems with the longest orbital periods. They are typically formed by a white dwarf, a red giant and a nebula. These objects are natural astrophysical laboratories for studying the evolution of binaries. Current estimates of the population of Milky Way symbiotic stars vary from 3000 up to 400000. However, the current census is less than 300. The Large sky Area Multi-Object fiber Spectroscopic Telescope (LAMOST) survey can obtain hundreds of thousands of stellar spectra per year, providing a good opportunity to search for new symbiotic stars. In this work we detect 4 of such binaries among 4,147,802 spectra released by the LAMOST, of which two are new identifications. The first is LAMOST J12280490-014825.7, considered to be an S-type halo symbiotic star. The second is LAMOST J202629.80+423652.0, a D-type symbiotic star