Machine Learning Analysis Identifies DrosophilaGrunge/Atrophin as an Important Learning and Memory Gene Required for Memory Retention and Social Learning.

G3 (Bethesda). 2017 Sep 09;:

Authors: Kacsoh BZ, Greene CS, Bosco G

Abstract
High throughput experiments are becoming increasingly common, and scientists must balance hypothesis driven experiments with genome wide data acquisition. We sought to predict novel genes involved in Drosophila learning and long-term memory from existing public high-throughput data. We performed an analysis using PILGRM, which analyzes public gene expression compendia using machine learning. We evaluated the top prediction alongside genes involved in learning and memory in IMP, an interface for functional relationship networks. We identified Grunge/Atrophin (Gug/Atro), a transcriptional repressor, histone deacetylase, as our top candidate. We find, through multiple, distinct assays, that Gug has an active role as a modulator of memory retention in the fly and its function is required in the adult mushroom body. Depletion of Gug specifically in neurons of the adult mushroom body, after cell division and neuronal development is complete, suggests that Gug function is important for memory retention through regulation of neuronal activity, and not by altering neurodevelopment. Our study provides a previously uncharacterized role for Gug as a possible regulator of neuronal plasticity at the interface of memory retention and memory extinction.

PMID: 28889104 [PubMed - as supplied by publisher]

A global Staphylococcus aureus proteome resource applied to the in vivo characterization of host-pathogen interactions.

Sci Rep. 2017 Sep 08;7(1):9718

Authors: Michalik S, Depke M, Murr A, Gesell Salazar M, Kusebauch U, Sun Z, Meyer TC, Surmann K, Pförtner H, Hildebrandt P, Weiss S, Palma Medina LM, Gutjahr M, Hammer E, Becher D, Pribyl T, Hammerschmidt S, Deutsch EW, Bader SL, Hecker M, Moritz RL, Mäder U, Völker U, Schmidt F

Abstract
Data-independent acquisition mass spectrometry promises higher performance in terms of quantification and reproducibility compared to data-dependent acquisition mass spectrometry methods. To enable high-accuracy quantification of Staphylococcus aureus proteins, we have developed a global ion library for data-independent acquisition approaches employing high-resolution time of flight or Orbitrap instruments for this human pathogen. We applied this ion library resource to investigate the time-resolved adaptation of S. aureus to the intracellular niche in human bronchial epithelial cells and in a murine pneumonia model. In epithelial cells, abundance changes for more than 400 S. aureus proteins were quantified, revealing, e.g., the precise temporal regulation of the SigB-dependent stress response and differential regulation of translation, fermentation, and amino acid biosynthesis. Using an in vivo murine pneumonia model, our data-independent acquisition quantification analysis revealed for the first time the in vivo proteome adaptation of S. aureus. From approximately 2.15 × 10(5)  S. aureus cells, 578 proteins were identified. Increased abundance of proteins required for oxidative stress response, amino acid biosynthesis, and fermentation together with decreased abundance of ribosomal proteins and nucleotide reductase NrdEF was observed in post-infection samples compared to the pre-infection state.

PMID: 28887440 [PubMed - in process]

ATG5 mediates a positive feedback loop between Wnt signaling and autophagy in melanoma.

Cancer Res. 2017 Sep 08;:

Authors: Ndoye A, Budina-Kolomets A, Kugel CH, Webster MR, Kaur A, Behera R, Rebecca VW, Li L, Brafford PA, Liu Q, Vashisht Gopal YN, Davies MA, Mills GB, Xu X, Wu H, Herlyn M, Nicastri MC, Winkler JD, Soengas MS, Amaravadi RK, Murphy ME, Weeraratna AT

Abstract
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin. To define the physiological relevance of this loop, melanoma cells with different Wnt status were treated in vitro and in vivo with the potent lysosomotropic compound Lys05. Wnt5Ahigh cells were less sensitive to Lys05 and could be reverted by inducing β -catenin activity. Our results suggest the efficacy of autophagy inhibitors might be improved by taking the Wnt signature of melanoma cells into account.

PMID: 28887323 [PubMed - as supplied by publisher]

Proteomic comparison of three clinical diarrhoeagenic drug-resistant Escherichia coli isolates grown on CHROMagar™STEC media.

J Proteomics. 2017 Sep 05;:

Authors: Kalule JB, Fortuin S, Calder B, Robberts L, Keddy KH, Nel A, Garnett S, Nicol M, Warner DF, Soares NC, Blackburn JM

Abstract
Shiga-toxin-producing Escherichia coli (STEC) and enteropathogenic Escherichia coli (EPEC) are key diarrhoea-causing foodborne pathogens. We used proteomics to characterize the virulence and antimicrobial resistance protein profiles of three clinical pathogenic E. coli isolates (two EPEC [one resistant to ciprofloxacin] and one STEC) cultured on CHROMagar™STEC solid media after minimal laboratory passage. We identified 4767 unique peptides from 1630 protein group across all three clinical E. coli strains. Label-free proteomic analysis allowed the identification of virulence and drug resistance proteins that were unique to each of the clinical isolates compared in this study. The B subunit of Shiga toxin, ToxB, was uniquely detected in the STEC strain while several other virulence factors including SheA, OmpF, OmpC and OmpX were significantly more abundant in the STEC strain. The ciprofloxacin resistant EPEC isolate possessed reduced levels of key virulence proteins compared to the ciprofloxacin susceptible EPEC and STEC strains. Parallel reaction monitoring assays validated the presence of biologically relevant proteins across biologically-replicated cultures. Propagation of clinical isolates on a relevant solid medium followed by mass spectrometry analysis represents a convenient means to quantify virulence factors and drug resistance determinants that might otherwise be lost through extensive in vitro passage in enteropathogenic bacteria.
SIGNIFICANCE: Through the use of quantitative proteomics, we have characterized the virulence and antimicrobial resistance attributes of three clinically isolated, pathogenic E. coli strains cultured on solid media. Our results provide new, quantitative data on the expressed proteomes of these tellurite-resistant, diarrhoeagenic E. coli strains and reveal a subset of antimicrobial resistance and virulence proteins that are differentially abundant between these clinical strains. Our quantitative proteomics-based approach should thus have applicability in microbiological diagnostic labs for the identification of pathogenic/drug resistant E. coli in the future.

PMID: 28887208 [PubMed - as supplied by publisher]

Integrative analysis of DNA methylation and mRNA expression during differentiation of umbilical cord blood derived mononuclear cells to endothelial cells.

Gene. 2017 Sep 05;:

Authors: Jeong Y, Jun Y, Kim J, Park H, Choi KS, Zhang H, Park JA, Kwon JY, Kim YM, Lee S, Kwon YG

Abstract
Differentiation of umbilical cord blood derived mononuclear cells to endothelial cells is accompanied by massive changes in gene expression. Although methylation and demethylation of DNA likely play crucial roles in regulating gene expression, their interplay during differentiation remains elusive. To address this question, we performed deep sequencing of DNA methylation and mRNA expression to profile global changes in promoter methylation and gene expression during differentiation from mononuclear cells to outgrowing cells. We identified 61 downregulated genes with hypermethylation, including CD74, VAV1, TLR8, and NCF4, as well as 21 upregulated genes with hypomethylation, including ECSCR, MCAM, PGF, and ARHGEF15. Interestingly, gene ontology analysis showed that downregulated genes with hypermethylation were enriched in immune-related functions, and upregulated genes with hypomethylation were enriched in the developmental process and angiogenesis, indicating the important roles of DNA methylation in regulating differentiation. We performed polymerase chain reaction analyses and bisulfite sequencing of representative genes (CD74, VAV1, ECSCR, and MCAM) to verify the negative correlation between DNA methylation and gene expression. Further, inhibition of DNA methyltransferase and demethylase activities using 5'-aza-dc and shRNAs, specific for TET1 and TET2 mRNAs, respectively, revealed that DNA methylation was the main regulator of the reversible expression of functionally important genes. Collectively, our findings implicate DNA methylation as a critical regulator of gene expression during umbilical cord blood derived mononuclear cells to endothelial cell differentiation.

PMID: 28887159 [PubMed - as supplied by publisher]

Beyond Read-Counts: Ribo-seq Data Analysis to Understand the Functions of the Transcriptome.

Trends Genet. 2017 Sep 05;:

Authors: Calviello L, Ohler U

Abstract
By mapping the positions of millions of translating ribosomes in the cell, ribosome profiling (Ribo-seq) has established its role as a powerful tool to study gene expression. Several laboratories have introduced modifications to the experimental protocol and expanded the repertoire of biochemical methods to study translation transcriptome-wide. However, the diversity of protocols highlights a need for standardization. At the same time, different computational analysis strategies have used Ribo-seq data to identify the set of translated sequences with high confidence. In this review we present an overview of such methodologies, outlining their assumptions, data requirements, and availability. At the interface between RNA and proteins, Ribo-seq can complement data from multiple omics approaches, zooming in on the central role of translation in the molecular cell.

PMID: 28887026 [PubMed - as supplied by publisher]

DNA Sensing across the Tree of Life.

Trends Immunol. 2017 Sep 05;:

Authors: Gallucci S, Maffei ME

Abstract
From plants to mammals, pattern recognition receptors (PRRs) specifically recognize DNA, as a potential marker of either infection or damage. These receptors play critical roles in inflammation, immunity, and pathogen resistance. Importantly, given the ubiquity of DNA, its sensing must be tightly regulated. DNA localization plays a key role in recognition, as highlighted by Toll-like receptor 9 (TLR9) in the endosomal compartment and cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) in the cytoplasm. Sequence and structure also enhance recognition across species. Evidence in plants supports the sensing of extracellular DNA by PRRs, leading to calcium-dependent signaling, although no receptor has been definitively identified yet. Here, we review the shared and distinct features of DNA sensors, and their physiological functions, across the tree of life.

PMID: 28886908 [PubMed - as supplied by publisher]

Identification of high-confidence RNA regulatory elements by combinatorial classification of RNA-protein binding sites.

Genome Biol. 2017 Sep 08;18(1):169

Authors: Li YE, Xiao M, Shi B, Yang YT, Wang D, Wang F, Marcia M, Lu ZJ

Abstract
Crosslinking immunoprecipitation sequencing (CLIP-seq) technologies have enabled researchers to characterize transcriptome-wide binding sites of RNA-binding protein (RBP) with high resolution. We apply a soft-clustering method, RBPgroup, to various CLIP-seq datasets to group together RBPs that specifically bind the same RNA sites. Such combinatorial clustering of RBPs helps interpret CLIP-seq data and suggests functional RNA regulatory elements. Furthermore, we validate two RBP-RBP interactions in cell lines. Our approach links proteins and RNA motifs known to possess similar biochemical and cellular properties and can, when used in conjunction with additional experimental data, identify high-confidence RBP groups and their associated RNA regulatory elements.

PMID: 28886744 [PubMed - in process]

40 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

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"systems biology"

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"systems biology"

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38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/09/08

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Relying on known or exploring for new? Movement patterns and reproductive resource use in a tadpole-transporting frog.

PeerJ. 2017;5:e3745

Authors: Beck KB, Loretto MC, Ringler M, Hödl W, Pašukonis A

Abstract
Animals relying on uncertain, ephemeral and patchy resources have to regularly update their information about profitable sites. For many tropical amphibians, widespread, scattered breeding pools constitute such fluctuating resources. Among tropical amphibians, poison frogs (Dendrobatidae) exhibit some of the most complex spatial and parental behaviors-including territoriality and tadpole transport from terrestrial clutches to ephemeral aquatic deposition sites. Recent studies have revealed that poison frogs rely on spatial memory to successfully navigate through their environment. This raises the question of when and how these frogs gain information about the area and suitable reproductive resources. To investigate the spatial patterns of pool use and to reveal potential explorative behavior, we used telemetry to follow males of the territorial dendrobatid frog Allobates femoralis during tadpole transport and subsequent homing. To elicit exploration, we reduced resource availability experimentally by simulating desiccated deposition sites. We found that tadpole transport is strongly directed towards known deposition sites and that frogs take similar direct paths when returning to their home territory. Frogs move faster during tadpole transport than when homing after the deposition, which probably reflects different risks and costs during these two movement phases. We found no evidence for exploration, neither during transport nor homing, and independent of the availability of deposition sites. We suggest that prospecting during tadpole transport is too risky for the transported offspring as well as for the transporting male. Relying on spatial memory of multiple previously discovered pools appears to be the predominant and successful strategy for the exploitation of reproductive resources in A. femoralis. Our study provides for the first time a detailed description of poison frog movement patterns during tadpole transport and corroborates recent findings on the significance of spatial memory in poison frogs. When these frogs explore and discover new reproductive resources remains unknown.

PMID: 28875083 [PubMed]

Somatic Embryogenesis in Coffee: The Evolution of Biotechnology and the Integration of Omics Technologies Offer Great Opportunities.

Front Plant Sci. 2017;8:1460

Authors: Campos NA, Panis B, Carpentier SC

Abstract
One of the most important crops cultivated around the world is coffee. There are two main cultivated species, Coffea arabica and C. canephora. Both species are difficult to improve through conventional breeding, taking at least 20 years to produce a new cultivar. Biotechnological tools such as genetic transformation, micropropagation and somatic embryogenesis (SE) have been extensively studied in order to provide practical results for coffee improvement. While genetic transformation got many attention in the past and is booming with the CRISPR technology, micropropagation and SE are still the major bottle neck and urgently need more attention. The methodologies to induce SE and the further development of the embryos are genotype-dependent, what leads to an almost empirical development of specific protocols for each cultivar or clone. This is a serious limitation and excludes a general comprehensive understanding of the process as a whole. The aim of this review is to provide an overview of which achievements and molecular insights have been gained in (coffee) somatic embryogenesis and encourage researchers to invest further in the in vitro technology and combine it with the latest omics techniques (genomics, transcriptomics, proteomics, metabolomics, and phenomics). We conclude that the evolution of biotechnology and the integration of omics technologies offer great opportunities to (i) optimize the production process of SE and the subsequent conversion into rooted plantlets and (ii) to screen for possible somaclonal variation. However, currently the usage of the latest biotechnology did not pass the stage beyond proof of potential and needs to further improve.

PMID: 28871271 [PubMed]

Effects of Enzymatically Depolymerized Low Molecular Weight Heparins on CCl4-Induced Liver Fibrosis.

Front Pharmacol. 2017;8:514

Authors: Yan Y, Guan C, Du S, Zhu W, Ji Y, Su N, Mei X, He D, Lu Y, Zhang C, Xing XH

Abstract
With regard to identifying the effective components of LMWH drugs curing hepatic fibrosis disease, we carried out a comparative study on the efficacy of enzymatically depolymerized LMWHs on CCl4 induced mouse liver fibrosis. The results showed that the controlled enzymatic depolymerization conditions resulted in LMWHs with significantly different activities. The LMWH product depolymerized by Heparinase I (I-11) with a Mw of 7160, exhibited a significant advantage in reducing the liver inflammation by suppressing TNF-α and IL-1β secretion, and minimizing hepatic fibrogenesis. The products prepared by only Heparinase II (II-11), and combined Heparinase III and II (III-II-5) showed limited positive effect on hepatic inflammation and fibrosis. On the contrary, the products by combined Heparinase III and I (III-I-9, III-I-5) showed no effect or stimulation effect on the hepatic fibrogenesis. Our results provided the basis for structure-activity relationship insight for inhibition of liver fibrosis activities of LMWHs, which might have significant implications for generic anti-fibrosis disease drug development.

PMID: 28871223 [PubMed]

16 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"systems biology"

These pubmed results were generated on 2017/09/05

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

From shaping organelles to signalling platforms: the emerging functions of plant ER-PM contact sites.

Curr Opin Plant Biol. 2017 Aug 31;40:89-96

Authors: Bayer EM, Sparkes I, Vanneste S, Rosado A

Abstract
The plant endoplasmic reticulum (ER) defines the biosynthetic site of lipids and proteins destined for secretion, but also contains important signal transduction and homeostasis components that regulate multiple hormonal and developmental responses. To achieve its various functions, the ER has a unique architecture, both reticulated and highly plastic, that facilitates the spatial-temporal segregation of biochemical reactions and the establishment of inter-organelle communication networks. At the cell cortex, the cortical ER (cER) anchors to and functionally couples with the PM through largely static structures known as ER-PM contact sites (EPCS). These spatially confined microdomains are emerging as critical regulators of the geometry of the cER network, and as highly specialized signalling hubs. In this review, we share recent insights into how EPCS regulate cER remodelling, and discuss the proposed roles for plant EPCS components in the integration of environmental and developmental signals at the cER-PM interface.

PMID: 28865976 [PubMed - as supplied by publisher]

Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease.

J Photochem Photobiol B. 2017 Aug 24;175:109-124

Authors: Kurian P, Obisesan TO, Craddock TJA

Abstract
Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. Classically, mitochondrial dysfunction has been viewed as the major source of oxidative stress and has been shown to precede tau and amyloid pathology in various dementias, but the exact mechanisms are not clear. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. While of low intensity, surrounding proteins within the cytosol can still absorb these energetic photons via aromatic amino acids (e.g., tryptophan and tyrosine). One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly co-localized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy to protect the cell from potentially harmful effects. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales and neuronal fine structure. Since microtubule networks are compromised in tauopathic diseases such as Alzheimer's and Parkinson's dementias, patients with these illnesses would be unable to support effective channeling of these photons for signaling or dissipation. Consequent emission surplus due to increased UPE production or decreased ability to absorb and transfer may lead to increased cellular oxidative damage, thus hastening the neurodegenerative process.

PMID: 28865316 [PubMed - as supplied by publisher]

PhenoGraph and viSNE Facilitate the Identification of Abnormal T-Cell Populations in Routine Clinical Flow Cytometric Data.

Cytometry B Clin Cytom. 2017 Sep 02;:

Authors: DiGiuseppe JA, Cardinali JL, Rezuke WN, Pe'er D

Abstract
BACKGROUND: Flow cytometric identification of neoplastic T-cell populations is complicated by the wide range of phenotypic abnormalities in T-cell neoplasia, and the diverse repertoire of reactive T-cell phenotypes. We evaluated whether a recently described clustering algorithm, PhenoGraph, and dimensionality-reduction algorithm, viSNE, might facilitate the identification of abnormal T-cell populations in routine clinical flow cytometric data.
METHODS: We applied PhenoGraph and viSNE to peripheral blood mononuclear cells labeled with a single 8-color T/NK-cell antibody combination. Individual peripheral blood samples containing either a T-cell neoplasm or reactive lymphocytosis were analyzed together with a cohort of 10 normal samples, which established the location and identity of normal mononuclear-cell subsets in viSNE displays.
RESULTS: PhenoGraph-derived subpopulations from the normal samples formed regions of phenotypic similarity in the viSNE display describing normal mononuclear-cell subsets, which correlated with those obtained by manual gating (r(2) = 0.99, p < 0.0001). In 24 of 24 cases of T-cell neoplasia with an aberrant phenotype, compared with 4 of 17 cases of reactive lymphocytosis (p = 1.4 x 10(-7) , Fisher Exact test), PhenoGraph-derived subpopulations originating exclusively from the abnormal sample formed one or more distinct phenotypic regions in the viSNE display, which represented the neoplastic T cells, and reactive T-cell subpopulations not present in the normal cohort, respectively. The numbers of neoplastic T cells identified using PhenoGraph/viSNE correlated with those obtained by manual gating (r(2) = 0.99; p < 0.0001).
CONCLUSIONS: PhenoGraph and viSNE may facilitate the identification of abnormal T-cell populations in routine clinical flow cytometric data. This article is protected by copyright. All rights reserved.

PMID: 28865188 [PubMed - as supplied by publisher]

Genome Characterization of Oleaginous Aspergillus oryzae BCC7051: A Potential Fungal-Based Platform for Lipid Production.

Curr Microbiol. 2017 Sep 01;:

Authors: Thammarongtham C, Nookaew I, Vorapreeda T, Srisuk T, Land ML, Jeennor S, Laoteng K

Abstract
The selected robust fungus, Aspergillus oryzae strain BCC7051 is of interest for biotechnological production of lipid-derived products due to its capability to accumulate high amount of intracellular lipids using various sugars and agro-industrial substrates. Here, we report the genome sequence of the oleaginous A. oryzae BCC7051. The obtained reads were de novo assembled into 25 scaffolds spanning of 38,550,958 bps with predicted 11,456 protein-coding genes. By synteny mapping, a large rearrangement was found in two scaffolds of A. oryzae BCC7051 as compared to the reference RIB40 strain. The genetic relationship between BCC7051 and other strains of A. oryzae in terms of aflatoxin production was investigated, indicating that the A. oryzae BCC7051 was categorized into group 2 nonaflatoxin-producing strain. Moreover, a comparative analysis of the structural genes focusing on the involvement in lipid metabolism among oleaginous yeast and fungi revealed the presence of multiple isoforms of metabolic enzymes responsible for fatty acid synthesis in BCC7051. The alternative routes of acetyl-CoA generation as oleaginous features and malate/citrate/pyruvate shuttle were also identified in this A. oryzae strain. The genome sequence generated in this work is a dedicated resource for expanding genome-wide study of microbial lipids at systems level, and developing the fungal-based platform for production of diversified lipids with commercial relevance.

PMID: 28865010 [PubMed - as supplied by publisher]